Autoimmune Hepatitis

Autoimmune MONDO:0016264 Pathograph 24 Show in embeddings browser Autoimmune Disease Liver Disease

Autoimmune hepatitis (AIH) is an idiopathic immune-mediated necroinflammatory liver disease with a clinical spectrum from asymptomatic biochemical abnormalities to acute liver failure. Diagnosis requires clinicopathologic integration of serum aminotransferases, IgG, autoantibodies, liver histology, and exclusion of competing causes; no single finding is pathognomonic. Persistent untreated inflammation can lead to fibrosis, cirrhosis, and end-stage liver failure. ANA/SMA and anti-LKM1/LC1 patterns were historically called types 1 and 2, but current EASL guidance no longer recommends those serologic profiles as clinically distinct subtypes requiring different treatment strategies.

Ask OpenScientist

Ask a research question about Autoimmune Hepatitis. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

6
Pathophys.
1
Histopath.
5
Phenotypes
2
Hypotheses
3
Gaps
24
Pathograph
3
Genes
4
Medical Actions
5
Differentials
1
Datasets
8
Trials
18
References
2
Deep Research
🏷

Classifications

Harrison's Part
GASTROINTESTINAL IMMUNE RHEUMATOLOGIC
◈

Mechanistic Hypotheses

2
HLA-linked loss of tolerance and adaptive hepatocyte injury
canonical_adaptive_autoimmunity CANONICAL
Evidence balance 1 support
Polygenic susceptibility and incompletely defined triggers permit a liver-autoantigen-directed adaptive response that produces hepatocyte injury, interface hepatitis, and—when persistent—fibrosis and cirrhosis.
Pathograph links
Polygenic HLA-linked susceptibility -> Liver-autoantigen-specific adaptive immune activation INDIRECT UNKNOWN INTERMEDIATES Genetic susceptibility, together with incompletely defined triggers and tolerance failure, permits an adaptive response against liver autoantigens. Intermediates: Environmental triggers are not defined for most patients.; The steps converting HLA-associated risk into loss of self-tolerance remain incompletely resolved.
Liver-autoantigen-specific adaptive immune activation -> Autoantibody and hyper-IgG response DIRECT Cognate B-cell antigen presentation and T-cell help support affinity-matured autoantibody production and the polyclonal IgG response.
Liver-autoantigen-specific adaptive immune activation -> T-cell-mediated hepatocyte injury UNKNOWN The autoreactive response is modeled as driving hepatocyte injury through effector T-cell and cytokine pathways; the precise dominant cytotoxic subset and antigenic targets remain incompletely mapped in human liver.
Liver-autoantigen-specific adaptive immune activation -> Arthralgia INDIRECT UNKNOWN INTERMEDIATES Joint pain is an extrahepatic symptom of AIH, but the intermediates linking liver-directed adaptive autoimmunity to arthralgia are not established.
T-cell-mediated hepatocyte injury -> Interface hepatitis and hepatocellular necroinflammation DIRECT Persistent adaptive immune injury produces periportal/interface inflammation and hepatocyte necroinflammation.
Interface hepatitis and hepatocellular necroinflammation -> Fatigue INDIRECT UNKNOWN INTERMEDIATES Systemic consequences of inflammatory liver disease can manifest as fatigue, although the responsible intermediates are not resolved.
Interface hepatitis and hepatocellular necroinflammation -> Jaundice INDIRECT KNOWN INTERMEDIATES Hepatocellular dysfunction can impair bilirubin handling and produce jaundice. Intermediates: Impaired hepatic bilirubin uptake, conjugation, or excretion
Interface hepatitis and hepatocellular necroinflammation -> Acute hepatic failure DIRECT Severe, rapidly progressive hepatocyte necrosis can cause acute liver failure at presentation.
Interface hepatitis and hepatocellular necroinflammation -> Chronic hepatic fibrogenesis INDIRECT KNOWN INTERMEDIATES Persistent necroinflammation stimulates progressive hepatic matrix deposition; effective treatment can halt or reverse part of this process. Intermediates: Hepatic stellate-cell activation; Excess extracellular-matrix deposition
Chronic hepatic fibrogenesis -> Cirrhosis DIRECT Advanced fibrotic remodeling produces cirrhotic liver architecture.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"AIH arises in genetically predisposed individuals when a trigger, such as exposure to a virus, leads to a T cell-mediated autoimmune response directed against liver autoantigens; this immune response is permitted by inadequate regulatory immune control leading to a loss of tolerance."
The disease primer states the canonical genetic-trigger-tolerance-adaptive immunity model.
Antigen-specific B-cell amplification of adaptive autoimmunity
b_cell_amplification EMERGING
Evidence balance 2 support
Autoreactive B cells may amplify AIH through cognate antigen presentation, cytokine interactions, and antibody production. Antigen-specific human clonal data support this route, but the direct pathogenic contribution of circulating autoantibodies and the clinical benefit of selective B-cell targeting remain unresolved.
Pathograph links
Liver-autoantigen-specific adaptive immune activation -> Autoantibody and hyper-IgG response DIRECT Cognate B-cell antigen presentation and T-cell help support affinity-matured autoantibody production and the polyclonal IgG response.
Show evidence (2 references)
PMID:39817450 SUPPORT Human Clinical
"SepSecS-specific B cell clones, but not those of unrelated specificities, were able to present soluble SepSecS to specific T cells."
Primary human clonal data directly demonstrate cognate autoantigen presentation by B cells.
PMID:31226726 SUPPORT Other
"Autoreactive B cells can promote autoimmunity through antigen presentation to autoreactive T cells, production of autoantibodies, generation of cytokines promoting T cell activation and differentiation, and inhibition of regulatory T cells and B cells."
This review supplies plausible amplification routes but covers several autoimmune liver diseases and does not establish AIH-specific causality for every route.
?

Discussions and Knowledge Gaps

3
Does selective BAFF or CD19-directed B-cell therapy safely improve durable biochemical control and reduce glucocorticoid exposure in AIH?
KNOWLEDGE GAP OPEN gap_b_cell_targeting_clinical_benefit
Attached to
pathophysiology#Autoantibody and hyper-IgG response pathophysiology#Liver-autoantigen-specific adaptive immune activation
Antigen-specific B-cell presentation is demonstrated in human samples, but direct antibody pathogenicity and clinical benefit from B-cell targeting remain unproven. BELief and MERCURY are testing two distinct B-cell-directed strategies; registry protocols must not be interpreted as positive results.
Show evidence (3 references)
PMID:39817450 SUPPORT Human Clinical
"SepSecS-specific B cell clones, but not those of unrelated specificities, were able to present soluble SepSecS to specific T cells."
Human clonal data establish the biologic rationale for testing B-cell targeting.
clinicaltrials:NCT06381453 SUPPORT Other
"Belimumab is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator."
The ongoing protocol tests BAFF inhibition but provides no efficacy result.
clinicaltrials:NCT07598825 SUPPORT Other
"The main objectives of this trial are to evaluate the safety and tolerability of inebilizumab in participants with autoimmune hepatitis (AIH) (Part 1) and to evaluate the efficacy of inebilizumab on AIH disease activity and glucocorticoid (GC) use in the management of AIH (Part 2)."
The ongoing protocol defines the CD19-directed question without supplying an answer.
Which immune states are reproducibly enriched in AIH liver tissue, and how do they relate to matched blood, disease activity, ancestry, and treatment response at donor level?
KNOWLEDGE GAP OPEN gap_paired_liver_blood_single_cell_resolution
Attached to
pathophysiology#Liver-autoantigen-specific adaptive immune activation pathophysiology#T-cell-mediated hepatocyte injury
The public AIH single-cell dataset pools four donors per condition into two PBMC libraries. It cannot estimate donor heterogeneity and samples blood, not the injured liver. A multi-ancestry longitudinal study with paired liver and blood single-cell/spatial profiling is needed before peripheral monocyte or NK signatures are promoted to causal liver mechanisms.
Show evidence (1 reference)
PMID:38340154 SUPPORT Human Clinical
"We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq."
The publication directly establishes the pooled peripheral design that creates the inference gap.
Should budesonide remain represented as a current first-line corticosteroid option for AIH?
INTERPRETATION RESOLVED interpretation_budesonide_guideline_reversal
Attached to
treatments#Prednisone or prednisolone-based corticosteroid induction
A 2010 randomized trial favored budesonide plus azathioprine in patients explicitly selected to have no cirrhosis, but the official 2025 EASL update no longer endorses budesonide because of safety and effectiveness concerns. Current representation must follow the newer guidance while preserving the historical trial boundary.
Resolved 2026-07-21T00:00:00Z
Resolution: Budesonide was removed from the current first-line treatment description; prednisone/prednisolone remain represented, and the older noncirrhotic trial is retained here for provenance.
Show evidence (2 references)
PMID:20600032 SUPPORT Human Clinical
"We performed a 6-month, prospective, double-blind, randomized, active-controlled, multicenter, phase IIb trial of patients with AIH without evidence of cirrhosis who were given budesonide (3 mg, three times daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients also received..."
The older trial supports efficacy only within a noncirrhotic study population and predates the current guidance.
url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/ SUPPORT Other
"Budesonide, which had previously been recommended as part of first-line therapy, is no longer endorsed due to concerns regarding its safety and overall effectiveness."
The official 2025 guideline summary resolves the current representation.
⚙

Pathophysiology

6
Polygenic HLA-linked susceptibility
Common germline variation creates a polygenic susceptibility rather than a Mendelian cause. HLA-DRB1*03:01 and *04:01 are major signals in European type-1-serology cohorts, while HLA-B*35:01 is the strongest signal in a Han Chinese cohort; these ancestry-dependent associations implicate antigen presentation. SH2B3 adds a non-HLA immune-signaling susceptibility signal.
HLA-linked loss of tolerance and adaptive hepatocyte injury
HLA-DRB1 hgnc:4948 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves HLA-DRB1 (hgnc:4948). hgnc:4948 is a gene from the HUGO Gene Nomenclature Committee. HLA-B hgnc:4932 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves HLA-B (hgnc:4932). hgnc:4932 is a gene from the HUGO Gene Nomenclature Committee. SH2B3 hgnc:29605 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves SH2B3 (hgnc:29605). hgnc:29605 is a gene from the HUGO Gene Nomenclature Committee.
Downstream
Liver-autoantigen-specific adaptive immune activation Genetic susceptibility, together with incompletely defined triggers and tolerance failure, permits an adaptive response against liver autoantigens. HLA-linked loss of tolerance and adaptive hepatocyte injury
Show evidence (2 references)
PMID:24768677 SUPPORT Human Clinical
"Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype."
A replicated European GWAS identifies the two principal HLA-DRB1 susceptibility alleles.
PMID:38089552 SUPPORT Human Clinical
"Stepwise conditional analysis revealed the strongest allele was in the HLA-B gene (HLA-B*35:01, p = 8.17×10-304; OR = 7.32), with additional independent signals at HLA-B*08:01 (p = 1.35 × 10-33; OR = 4.26) and rs7765379 (p = 5.08 × 10-18; OR = 1.66)."
Fine mapping in 1,622 Chinese cases and matched controls establishes an ancestry-specific HLA-B susceptibility pattern.
Liver-autoantigen-specific adaptive immune activation
Autoreactive T and B cells recognize liver-associated self antigens. Human clonal analysis has directly demonstrated SepSecS/SLA-specific CD4 T cells and B cells, while also finding lower-level SepSecS-reactive T cells in controls; the response is therefore disease-associated but not by itself diagnostic or universally disease-specific.
Antigen-specific B-cell amplification of adaptive autoimmunity HLA-linked loss of tolerance and adaptive hepatocyte injury
CD4-positive, alpha-beta T cell CL:0000624 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves CD4-positive, alpha-beta T cell (CL:0000624). CL:0000624 is a cell type from the Cell Ontology. B cell CL:0000236 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves B cell (CL:0000236). CL:0000236 is a cell type from the Cell Ontology.
adaptive immune response GO:0002250 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves adaptive immune response (GO:0002250). GO:0002250 is a biological process from the Gene Ontology. T cell activation GO:0042110 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves T cell activation (GO:0042110). GO:0042110 is a biological process from the Gene Ontology. B cell activation GO:0042113 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves B cell activation (GO:0042113). GO:0042113 is a biological process from the Gene Ontology.
Downstream
Autoantibody and hyper-IgG response Cognate B-cell antigen presentation and T-cell help support affinity-matured autoantibody production and the polyclonal IgG response. HLA-linked loss of tolerance and adaptive hepatocyte injury Antigen-specific B-cell amplification of adaptive autoimmunity
T-cell-mediated hepatocyte injury The autoreactive response is modeled as driving hepatocyte injury through effector T-cell and cytokine pathways; the precise dominant cytotoxic subset and antigenic targets remain incompletely mapped in human liver. HLA-linked loss of tolerance and adaptive hepatocyte injury
Arthralgia Joint pain is an extrahepatic symptom of AIH, but the intermediates linking liver-directed adaptive autoimmunity to arthralgia are not established. HLA-linked loss of tolerance and adaptive hepatocyte injury
Show evidence (1 reference)
PMID:39817450 SUPPORT Human Clinical
"SepSecS-specific CD4+ T cell clones were found in patients with AIH who were anti-SLA-positive and anti-SLA-negative, and, to a lesser extent, in patients with non-AIH liver diseases and in healthy individuals."
Human clonal analysis directly supports an autoantigen-specific CD4 response while preserving its incomplete disease specificity.
Autoantibody and hyper-IgG response
Activated B-cell and plasma-cell lineages generate elevated IgG and characteristic ANA, SMA, anti-LKM1/LC1, and anti-SLA/SepSecS antibodies. These are diagnostically useful outputs of adaptive immunity; this graph does not assume that circulating autoantibodies directly injure hepatocytes.
B cell CL:0000236 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves B cell (CL:0000236). CL:0000236 is a cell type from the Cell Ontology. plasma cell CL:0000786 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves plasma cell (CL:0000786). CL:0000786 is a cell type from the Cell Ontology.
immunoglobulin production GO:0002377 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves immunoglobulin production (GO:0002377). GO:0002377 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:39817450 SUPPORT Human Clinical
"The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured compared with their germline versions, and recognized at least 3 nonoverlapping epitopes."
Human monoclonal antibodies directly demonstrate an affinity-matured IgG1 response to an AIH autoantigen.
T-cell-mediated hepatocyte injury
Liver-autoantigen-directed T-cell activation and inflammatory cytokine production promote hepatocyte injury and death. The prior record's claim that CD8 T cells recognize MHC class II on hepatocytes was removed: CD8 restriction is to MHC class I, and the available AIH evidence does not establish that erroneous route.
HLA-linked loss of tolerance and adaptive hepatocyte injury
T cell CL:0000084 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T cell (CL:0000084). CL:0000084 is a cell type from the Cell Ontology. hepatocyte CL:0000182 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves hepatocyte (CL:0000182). CL:0000182 is a cell type from the Cell Ontology.
T cell mediated cytotoxicity GO:0001913 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves T cell mediated cytotoxicity (GO:0001913). GO:0001913 is a biological process from the Gene Ontology. inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. apoptotic process GO:0006915 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves apoptotic process (GO:0006915). GO:0006915 is a biological process from the Gene Ontology.
liver UBERON:0002107 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in liver (UBERON:0002107). UBERON:0002107 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Interface hepatitis and hepatocellular necroinflammation Persistent adaptive immune injury produces periportal/interface inflammation and hepatocyte necroinflammation. HLA-linked loss of tolerance and adaptive hepatocyte injury
Show evidence (1 reference)
PMID:39817450 SUPPORT Human Clinical
"SepSecS-specific T cell clones from patients with AIH produced IFN-γ, IL-4, and IL-10, targeted multiple SepSecS epitopes, and, in one patient, were clonally expanded in both blood and liver biopsy."
The study supports cytokine-producing autoantigen-specific T cells and liver expansion in one patient, but not a universal CD8 cytotoxic route.
Interface hepatitis and hepatocellular necroinflammation
Immune-cell-rich interface hepatitis and periportal necroinflammation are the characteristic tissue injury pattern. Histology is central to diagnosis but is not independently pathognomonic.
HLA-linked loss of tolerance and adaptive hepatocyte injury
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
liver UBERON:0002107 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in liver (UBERON:0002107). UBERON:0002107 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Fatigue Systemic consequences of inflammatory liver disease can manifest as fatigue, although the responsible intermediates are not resolved. HLA-linked loss of tolerance and adaptive hepatocyte injury
Jaundice Hepatocellular dysfunction can impair bilirubin handling and produce jaundice. HLA-linked loss of tolerance and adaptive hepatocyte injury
Acute hepatic failure Severe, rapidly progressive hepatocyte necrosis can cause acute liver failure at presentation. HLA-linked loss of tolerance and adaptive hepatocyte injury
Chronic hepatic fibrogenesis Persistent necroinflammation stimulates progressive hepatic matrix deposition; effective treatment can halt or reverse part of this process. HLA-linked loss of tolerance and adaptive hepatocyte injury
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis."
The review directly identifies interface hepatitis and periportal necrosis as diagnostic tissue hallmarks.
Chronic hepatic fibrogenesis
Recurrent or persistent inflammatory injury drives extracellular-matrix accumulation and architectural remodeling of the liver. Advanced fibrosis culminates in cirrhosis and its complications.
HLA-linked loss of tolerance and adaptive hepatocyte injury
extracellular matrix organization GO:0030198 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves extracellular matrix organization (GO:0030198). GO:0030198 is a biological process from the Gene Ontology.
liver UBERON:0002107 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in liver (UBERON:0002107). UBERON:0002107 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Cirrhosis Advanced fibrotic remodeling produces cirrhotic liver architecture. HLA-linked loss of tolerance and adaptive hepatocyte injury
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed."
The review supports progressive fibrotic architectural disease when inflammation remains untreated.
✶

Histopathology

1
Interface hepatitis with periportal necrosis
Liver biopsy typically shows interface hepatitis and periportal necroinflammation. These findings support AIH only in the appropriate clinical and serologic context and are not independently pathognomonic.
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis."
The review directly identifies the characteristic diagnostic histology.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Autoimmune Hepatitis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Digestive 3
Jaundice HP:0000952 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Jaundice (HP:0000952). HP:0000952 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes SUPPORT Other
"Overview of symptoms and causes of autoimmune hepatitis. Symptoms may include fatigue, joint pain, nausea, poor appetite, pain over your liver, and jaundice."
The NIDDK clinical summary explicitly lists jaundice among AIH symptoms.
Acute hepatic failure HP:0006554 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acute hepatic failure (HP:0006554). HP:0006554 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40348684 SUPPORT Human Clinical
"At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis."
Current guidance directly identifies acute liver failure as an AIH presentation.
Cirrhosis HP:0001394 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cirrhosis (HP:0001394). HP:0001394 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed."
The review directly supports cirrhosis as a preventable advanced outcome.
Constitutional 2
Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes SUPPORT Other
"Overview of symptoms and causes of autoimmune hepatitis. Symptoms may include fatigue, joint pain, nausea, poor appetite, pain over your liver, and jaundice."
The NIDDK clinical summary explicitly lists fatigue among AIH symptoms.
Arthralgia HP:0002829 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arthralgia (HP:0002829). HP:0002829 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes SUPPORT Other
"Overview of symptoms and causes of autoimmune hepatitis. Symptoms may include fatigue, joint pain, nausea, poor appetite, pain over your liver, and jaundice."
The NIDDK clinical summary explicitly lists joint pain among AIH symptoms.
🧬

Genetic Associations

3
HLA-DRB1 susceptibility alleles (HLA-DRB1*03:01 primary and HLA-DRB1*04:01 secondary susceptibility in replicated European type-1-serology cohorts)
Gene: HLA-DRB1 hgnc:4948 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is HLA-DRB1 (hgnc:4948). hgnc:4948 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR variant_origin: GERMLINE
Show evidence (1 reference)
PMID:24768677 SUPPORT Human Clinical
"Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype."
The discovery and replication study supports the two European-cohort HLA-DRB1 susceptibility alleles.
HLA-B susceptibility alleles (HLA-B*35:01 and additional independent HLA-B signals in a Han Chinese type-1-serology cohort)
Gene: HLA-B hgnc:4932 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is HLA-B (hgnc:4932). hgnc:4932 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR variant_origin: GERMLINE
Show evidence (1 reference)
PMID:38089552 SUPPORT Human Clinical
"Stepwise conditional analysis revealed the strongest allele was in the HLA-B gene (HLA-B*35:01, p = 8.17×10-304; OR = 7.32), with additional independent signals at HLA-B*08:01 (p = 1.35 × 10-33; OR = 4.26) and rs7765379 (p = 5.08 × 10-18; OR = 1.66)."
The 15-center Chinese fine-mapping study directly supports the HLA-B*35:01 association and additional independent signals.
SH2B3 susceptibility variant (Non-HLA common-variant susceptibility signal (rs3184504) in a European GWAS)
Gene: SH2B3 hgnc:29605 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SH2B3 (hgnc:29605). hgnc:29605 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR variant_origin: GERMLINE
Show evidence (1 reference)
PMID:24768677 SUPPORT Human Clinical
"We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6))."
The GWAS directly supports SH2B3 as a non-HLA susceptibility locus.
💊

Medical Actions

4
Prednisone or prednisolone-based corticosteroid induction
Category: Therapeutic Action: corticosteroid agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is corticosteroid agent therapy, annotated with Systemic Corticosteroid Therapy (NCIT:C122080). NCIT:C122080 is a clinical intervention from the NCI Thesaurus. Ontology label: Systemic Corticosteroid Therapy NCIT:C122080
Systemic prednisone or prednisolone is used to induce remission, with dose and taper individualized to severity, response, and toxicity. Budesonide is deliberately not grouped into this current first-line entry; its older noncirrhotic trial and the 2025 guideline reversal are documented below.
Mechanism Target:
INHIBITS T-cell-mediated hepatocyte injury — Broad glucocorticoid immunosuppression reduces immune-mediated hepatocyte injury.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"Standard regimens include fairly high initial doses of corticosteroids (prednisone or prednisolone), which are tapered gradually as azathioprine is introduced."
Clinical use of corticosteroid induction supports suppression of the autoimmune-injury pathway, but this passage does not isolate a T-cell-specific pharmacodynamic effect.
INHIBITS Interface hepatitis and hepatocellular necroinflammation — Suppression of active inflammation is the induction target.
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"The aims of treatment are to induce and maintain long term remission of liver inflammation."
The review directly identifies remission of liver inflammation as the treatment target.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"Standard regimens include fairly high initial doses of corticosteroids (prednisone or prednisolone), which are tapered gradually as azathioprine is introduced."
The disease primer directly supports prednisone/prednisolone induction and tapering.
Azathioprine steroid-sparing therapy
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: azathioprine CHEBI:2948 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses azathioprine (CHEBI:2948). CHEBI:2948 is a therapeutic agent from Chemical Entities of Biological Interest.
Azathioprine is introduced as a steroid-sparing agent for maintenance or as part of combination induction, with patient-specific contraindication and toxicity assessment.
Mechanism Target:
INHIBITS Liver-autoantigen-specific adaptive immune activation — Antimetabolite immunosuppression reduces lymphocyte proliferation and supports steroid sparing.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"Standard regimens include fairly high initial doses of corticosteroids (prednisone or prednisolone), which are tapered gradually as azathioprine is introduced."
The standard steroid-sparing regimen supports modulation of the adaptive autoimmune pathway, although this passage does not directly measure lymphocyte proliferation.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"Standard regimens include fairly high initial doses of corticosteroids (prednisone or prednisolone), which are tapered gradually as azathioprine is introduced."
The review directly supports azathioprine as the steroid-sparing standard agent.
Mycophenolate mofetil immunosuppression
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: mycophenolate mofetil CHEBI:8764 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses mycophenolate mofetil (CHEBI:8764). CHEBI:8764 is a therapeutic agent from Chemical Entities of Biological Interest.
Mycophenolate mofetil (MMF) is a current first-line alternative to azathioprine and remains an option for intolerance or inadequate response. It is teratogenic and requires reproductive-risk counseling. The strongest direct comparison is a small 24-week, open-label adult trial, so long-term and broader-population comparative effectiveness remains less certain.
Mechanism Target:
INHIBITS Liver-autoantigen-specific adaptive immune activation — MMF suppresses lymphocyte proliferation and the adaptive autoimmune response.
Show evidence (1 reference)
PMID:38101756 SUPPORT Human Clinical
"The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022)."
The randomized comparison supports clinical pathway modulation by MMF, but it does not directly measure the proposed lymphocyte-level target.
Show evidence (2 references)
PMID:38101756 SUPPORT Human Clinical
"The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022)."
The randomized comparison supports higher 24-week biochemical remission with MMF plus prednisolone in this 70-patient open-label cohort.
url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/ SUPPORT Other
"Therapeutically, the updated guidelines introduce Mycophenolate mofetil as a viable and safe first-line alternative to azathioprine. It is now recognised for its comparable or even superior efficacy and reduced rate of adverse events. However, clinicians are cautioned about its teratogenic..."
The official EASL summary supports MMF as a first-line alternative and states the reproductive-safety caveat.
Liver transplantation
Category: Therapeutic Action: liver transplantationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is liver transplantation (NCIT:C15271). NCIT:C15271 is a clinical intervention from the NCI Thesaurus. Ontology label: Liver Transplantation NCIT:C15271
Liver transplantation is a rescue treatment for acute liver failure or decompensated end-stage disease when medical therapy cannot restore adequate function. AIH may recur after transplantation.
Target Phenotypes: Acute hepatic failure HP:0006554 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Acute hepatic failure (HP:0006554). HP:0006554 is a phenotype from the Human Phenotype Ontology. Cirrhosis HP:0001394 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Cirrhosis (HP:0001394). HP:0001394 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"Liver transplantation is a life-saving option for those who progress to end-stage liver disease, although AIH can recur or develop de novo after transplantation."
The primer supports transplantation for end-stage disease and the risk of post-transplant recurrence.
🔬

Biochemical Markers

6
Antinuclear antibodies (ANA) (Positive)
Context: Historical type-1 serologic pattern; not a current treatment-defining subtype
Pathograph Readouts
Readout Of Autoantibody and hyper-IgG response Positive Diagnostic
ANA positivity is a serologic readout of the adaptive autoantibody response, not proof of direct antibody-mediated hepatocyte injury.
Show evidence (1 reference)
PMID:20862497 SUPPORT Human Clinical
"In type 1 autoimmune hepatitis, the main circulating autoantibodies, although not specific for the disease, are antinuclear antibodies, smooth-muscle antibodies, and anti F-actin antibodies."
The review supports ANA as a circulating diagnostic readout of the autoantibody response while explicitly noting incomplete specificity.
Show evidence (1 reference)
PMID:20862497 SUPPORT Human Clinical
"In type 1 autoimmune hepatitis, the main circulating autoantibodies, although not specific for the disease, are antinuclear antibodies, smooth-muscle antibodies, and anti F-actin antibodies."
The review identifies ANA and explicitly notes incomplete specificity.
Smooth-muscle and F-actin antibodies (SMA) (Positive)
Context: Historical type-1 serologic pattern; not a current treatment-defining subtype
Pathograph Readouts
Readout Of Autoantibody and hyper-IgG response Positive Diagnostic
SMA/F-actin positivity reports the adaptive autoantibody response.
Show evidence (1 reference)
PMID:20862497 SUPPORT Human Clinical
"In type 1 autoimmune hepatitis, the main circulating autoantibodies, although not specific for the disease, are antinuclear antibodies, smooth-muscle antibodies, and anti F-actin antibodies."
The review supports SMA and anti-F-actin as circulating diagnostic readouts of the autoantibody response.
Show evidence (1 reference)
PMID:20862497 SUPPORT Human Clinical
"In type 1 autoimmune hepatitis, the main circulating autoantibodies, although not specific for the disease, are antinuclear antibodies, smooth-muscle antibodies, and anti F-actin antibodies."
The review identifies SMA/F-actin antibodies and explicitly notes incomplete specificity.
Anti-LKM1 and anti-LC1 antibodies (Positive)
Context: Historical type-2 serologic pattern; not a current treatment-defining subtype
Pathograph Readouts
Readout Of Autoantibody and hyper-IgG response Positive Diagnostic
Anti-LKM1/LC1 positivity reports a recognized AIH serologic pattern.
Show evidence (1 reference)
PMID:20862497 SUPPORT Human Clinical
"In type 2 autoimmune hepatitis, a disease which occurs predominantly in girls and young women, anti-liver-kidney microsomal-1 antibodies and anti-cytosol-1 antibodies are the major circulating autoantibodies."
The review supports anti-LKM1 and anti-LC1 as circulating diagnostic readouts of a recognized AIH serologic pattern.
Show evidence (1 reference)
PMID:20862497 SUPPORT Human Clinical
"In type 2 autoimmune hepatitis, a disease which occurs predominantly in girls and young women, anti-liver-kidney microsomal-1 antibodies and anti-cytosol-1 antibodies are the major circulating autoantibodies."
The review identifies anti-LKM1 and anti-LC1 as the historical type-2 serologic pattern.
Anti-SLA/SepSecS antibodies (Positive)
Context: Autoantibody directed against soluble liver antigen/SepSecS
Pathograph Readouts
Readout Of Autoantibody and hyper-IgG response Positive Diagnostic
Anti-SLA/SepSecS positivity reports an affinity-matured autoantigen-specific B-cell response.
Show evidence (1 reference)
PMID:39817450 SUPPORT Human Clinical
"The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured compared with their germline versions, and recognized at least 3 nonoverlapping epitopes."
The primary human study supports anti-SLA/SepSecS as a readout of an affinity-matured, autoantigen-specific B-cell response.
Show evidence (1 reference)
PMID:39817450 SUPPORT Human Clinical
"The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured compared with their germline versions, and recognized at least 3 nonoverlapping epitopes."
The primary human study directly characterizes affinity-matured anti-SepSecS antibodies.
Serum immunoglobulin G (IgG) (Elevated)
Context: Diagnostic and treatment-response biomarker; a normal value does not by itself exclude AIH
Pathograph Readouts
Readout Of Autoantibody and hyper-IgG response Positive Diagnostic
Increased serum IgG reports the humoral immune response and is used with other diagnostic findings.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology."
The disease primer directly supports increased serum IgG as a diagnostic readout used with serology and histology.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology."
The disease primer identifies increased IgG as a core diagnostic feature.
Serum ALT and AST (Elevated)
Context: Hepatocellular injury and biochemical-response biomarker
Pathograph Readouts
Readout Of Interface hepatitis and hepatocellular necroinflammation Positive Monitoring
Elevated aminotransferases report active hepatocellular injury but are not specific to AIH.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology."
The disease primer directly supports increased serum transaminases as a biochemical readout of active liver injury in the diagnostic context.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology."
The disease primer identifies increased serum transaminases as a core diagnostic feature.
🔬

Diagnosis

3
Integrated serum biochemistry and autoantibody evaluation
Measure serum ALT/AST and IgG and test an appropriate autoantibody panel (including ANA, SMA/F-actin, anti-LKM1/LC1, and anti-SLA when indicated). Results must be integrated with histology and competing-cause evaluation; neither seronegativity nor a normal IgG alone is modeled as exclusionary.
clinical laboratory procedure NCIT:C25294 NCI Thesaurus (NCIT)
Results: A compatible hepatocellular injury pattern, increased IgG, and characteristic autoantibodies support but do not independently establish AIH.
Show evidence (1 reference)
PMID:29644994 SUPPORT Human Clinical
"The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology."
The disease primer directly supports the integrated biochemical, serologic, and histologic diagnostic pattern.
Liver biopsy with histopathologic assessment
Liver biopsy assesses interface activity, periportal necrosis, fibrosis, and competing patterns. It remains a diagnostic cornerstone rather than a standalone disease-specific test.
biopsy of liver NCIT:C51677 NCI Thesaurus (NCIT)
Results: Interface hepatitis and periportal necroinflammation support AIH in the appropriate clinic-serologic context.
Show evidence (2 references)
PMID:36746473 SUPPORT Human Clinical
"A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis."
The clinical review directly supports the biopsy pattern within an integrated diagnosis.
url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/ SUPPORT Other
"These new standards are designed to support more consistent and standardised interpretation of liver biopsies, which remain a cornerstone of AIH diagnosis."
The official 2025 EASL summary explicitly retains liver biopsy as a diagnostic cornerstone.
Simplified International Autoimmune Hepatitis Group score
The simplified score combines autoantibodies, IgG, histology, and exclusion of viral hepatitis. A score of at least 6 supports probable AIH and at least 7 supports definite AIH; it supports clinical reasoning but does not replace expert assessment in atypical or acute-severe presentations.
clinical assessment NCIT:C124351 NCI Thesaurus (NCIT)
Results: In the original validation set, cutoff 6 had 88% sensitivity and 97% specificity; cutoff 7 had 81% sensitivity and 99% specificity.
Show evidence (2 references)
PMID:18537184 SUPPORT Human Clinical
"This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis."
The primary criteria study defines the four score components.
PMID:18537184 SUPPORT Human Clinical
"The score was found to have 88% sensitivity and 97% specificity (cutoff > or =6) and 81% sensitivity and 99% specificity (cutoff > or =7) in the validation set."
The primary validation supplies the cutoff performance characteristics.
📈

Progression

3
Asymptomatic or insidious presentation
Some patients are found through abnormal laboratory testing and do not pass through a fixed sequence of clinical stages.
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"The clinical presentation is often that of acute hepatitis, sometimes very severe; less frequently, it can be insidious or completely asymptomatic."
The review directly identifies insidious and asymptomatic presentations.
Acute or acute-severe presentation
Acute hepatitis, including acute liver failure, can be the initial presentation rather than a late phase of previously recognized disease.
Show evidence (1 reference)
PMID:40348684 SUPPORT Human Clinical
"At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis."
Current guidance identifies acute liver failure as part of the baseline spectrum.
Persistent inflammation with fibrosis and advanced liver disease
When diagnosis or effective treatment is delayed, chronic inflammation may progress to cirrhosis and end-stage liver failure. This is preventable in many patients and is not an inevitable stage.
Show evidence (1 reference)
PMID:36746473 SUPPORT Human Clinical
"Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed."
The review directly links delayed diagnosis and treatment to advanced liver disease.
📊

Prevalence

2
Global pooled estimate from population-based studies
Annual Incidence 1.28 per 100,000 (1.01–1.63) 1–9 per 100,000
Annual incidence per 100,000 inhabitant-years. Between-study heterogeneity was extreme (I2 99.51%), so the pooled value is not a universal regional rate.
Show evidence (1 reference)
PMID:37876996 SUPPORT Human Clinical
"Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample..."
The population-based meta-analysis supplies the pooled annual incidence, confidence interval, and heterogeneity used here.
Global pooled estimate from population-based studies
Point Prevalence 15.65 per 100,000 (13.42–18.24) 1–9 per 10,000
Pooled prevalence per 100,000 inhabitants. The estimate combines markedly heterogeneous populations (I2 99.75%) and the authors found evidence of publication bias and substantial geographic variation.
Show evidence (1 reference)
PMID:37876996 SUPPORT Human Clinical
"Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample..."
The meta-analysis supplies the pooled prevalence and confidence interval.
⚖️

Clinical Burden

Variable
Burden varies from asymptomatic disease to acute liver failure. Even clinically stable disease commonly requires long-term immunosuppression and repeated specialist follow-up; delayed treatment can permit cirrhosis and end-stage liver failure. Quality-of-life and mental-health burden may remain clinically important even in ambulatory patients.
Show evidence (3 references)
PMID:40348684 SUPPORT Human Clinical
"At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis."
Current guidance directly supports the very broad severity spectrum.
PMID:36746473 SUPPORT Human Clinical
"Most patients need lifelong maintenance therapy, and repeated follow-up in experienced hands improves the quality of care and quality of life for affected patients."
The review documents the chronic treatment and follow-up burden.
PMID:24240053 SUPPORT Human Clinical
"Based on patient-reported data, a major depressive syndrome (10.8%) was found to be five times more frequent in AIH patients compared to the general population (p<0.001)."
A single-center outpatient cohort supports an additional psychosocial burden but is not assumed to represent all populations.
🔀

Differential Diagnoses

5

Conditions with similar clinical presentations that must be differentiated from Autoimmune Hepatitis:

Viral hepatitis
Overlapping Features Acute or chronic viral hepatitis can produce the same hepatocellular enzyme pattern and overlapping histology. Virologic testing and exposure context are required before assigning idiopathic AIH.
Distinguishing Features
  • Positive pathogen-specific nucleic-acid or serologic evidence
  • Epidemiologic exposure context
  • Simplified AIH criteria explicitly require exclusion of viral hepatitis
Show evidence (1 reference)
PMID:18537184 SUPPORT Human Clinical
"This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis."
The validated diagnostic score explicitly requires viral-hepatitis exclusion.
Drug-induced autoimmune-like hepatitis
Overlapping Features Drug-induced liver injury may reproduce autoantibodies, increased IgG, and an autoimmune-like histologic pattern. The idiopathic AIH disease boundary used here excludes cases attributed to a drug or herb after temporal and causality assessment.
Distinguishing Features
  • Compatible medication or supplement exposure and latency
  • Improvement after withdrawal may support drug causality
  • Relapse behavior after immunosuppression withdrawal may differ, but is not by itself definitive
Show evidence (1 reference)
PMID:25574080 SUPPORT Other
"AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis."
The review explicitly requires exclusion of toxic causes, supporting the drug-induced boundary without supplying a complete causality algorithm.
Wilson disease MONDO:0010200
Overlapping Features Wilson disease can present as acute hepatitis, chronic hepatitis, or liver failure and must be excluded in compatible age groups and presentations.
Distinguishing Features
  • Copper studies and ATP7B evaluation support Wilson disease
  • Kayser-Fleischer rings or neurologic features may be present but are not required
  • Autoantibody positivity does not independently exclude Wilson disease
Show evidence (1 reference)
PMID:25574080 SUPPORT Other
"AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis."
The review requires exclusion of metabolic and genetic causes; Wilson disease is a key such mimic.
Primary biliary cholangitis, primary sclerosing cholangitis, and AIH variant syndromes
Overlapping Features Cholestatic biochemistry, bile-duct injury, cholangiography, and disease-specific serology may identify PBC, PSC, or an AIH variant syndrome. Variant/overlap taxonomy remains controversial and should not be treated as a simple autoantibody-defined AIH subtype.
Distinguishing Features
  • Antimitochondrial antibodies and small-duct cholangitis support PBC
  • Multifocal biliary stricturing and inflammatory bowel disease support PSC
  • Combined hepatitic and cholangiopathic findings may support a variant syndrome
Show evidence (1 reference)
PMID:20862497 SUPPORT Other
"There also are patients with variant forms of autoimmune hepatitis who have clinical and serologic findings of autoimmune hepatitis in addition to features of primary biliary cirrhosis or primary sclerosing cholangitis. The taxonomy and definitions of these variants, often referred to as overlap..."
The review supports the combined-feature variants and explicitly notes taxonomic uncertainty.
Immune checkpoint inhibitor-associated hepatitis
Overlapping Features Immune-mediated hepatitis after checkpoint blockade is a treatment-related immune adverse event, not idiopathic AIH, even though T-cell activation, transaminase elevation, and steroid responsiveness may overlap.
Distinguishing Features
  • Temporal relationship to immune checkpoint inhibitor exposure
  • Diagnosis of exclusion within an oncology treatment context
  • Histology and serology may differ from idiopathic AIH
Show evidence (1 reference)
DOI:10.3389/fphar.2022.1077468 SUPPORT Other
"Because of the lack of specific markers, a diagnosis of exclusion of IMH is critical."
The review supports checkpoint-inhibitor hepatitis as a diagnosis of exclusion defined by treatment exposure.
📊

Related Datasets

1
scRNA-seq for analyzing the characteristics of PBMC in patients with autoimmune hepatitis geo:GSE216064
Human peripheral-blood single-cell RNA-sequencing dataset comparing pooled PBMCs from four AIH patients with pooled PBMCs from four healthy controls.
Homo sapiens SINGLE CELL RNA SEQ n=2 10x Genomics Chromium 3' gene expression v2
peripheral blood mononuclear cells CL:0000842 Cell Ontology (CL) Relation: this dataset samples this sample type This dataset samples peripheral blood mononuclear cells, annotated with mononuclear leukocyte (CL:0000842). CL:0000842 is a sample type from the Cell Ontology.
Conditions: pooled PBMCs from four autoimmune hepatitis patients pooled PBMCs from four healthy controls
PMID:38340154
GEO contains two pooled assay libraries, not eight independent libraries. The eight biological donors were pooled into one AIH and one control library, preventing donor-level estimation and leaving liver-tissue causality unresolved. The publication reports 3,511 AIH and 3,690 control cell transcriptomes.
Show evidence (2 references)
GEO:GSE216064 SUPPORT Other
"This present study was designed to analyze the characteristics of AIH peripheral blood mononuclear cells (PBMCs) through single-cell RNA sequencing (scRNA-seq, 10x Genomics Gene Expression 3' Chromium V 2.0) and to explore the potential molecular mechanism of AIH."
GEO metadata directly supports the disease, sample type, and assay.
PMID:38340154 SUPPORT Human Clinical
"We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq."
The publication defines the donor pools and cell-transcriptome counts.
🔬

Clinical Trials

8
NCT02997878 PHASE_II ACTIVE_NOT_RECRUITING
MERLIN is an adaptive phase I/IIa, single-arm trial of one infusion of umbilical-cord-derived ORBCEL-C mesenchymal stromal cells. It enrolls PSC and AIH in distinct cohorts and includes AIH-specific ALT/IgG activity outcomes; 18 participants were enrolled overall.
Show evidence (1 reference)
clinicaltrials:NCT02997878 SUPPORT Other
"MERLIN is an adaptive, single arm, multi-centre, phase IIa multi-disease clinical trial."
The registry summary supports the adaptive early-phase multi-disease design.
NCT06381453 PHASE_II RECRUITING
BELief is an open-label multicenter study adding weekly belimumab, a monoclonal antibody that inhibits BAFF, to standard care in 48 adults with active disease or treatment-dependent remission. It tests steroid burden, biochemical control, safety, and exploratory immune biomarkers.
Show evidence (1 reference)
clinicaltrials:NCT06381453 SUPPORT Other
"Belimumab is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator."
The registry states the intervention and B-cell-targeting mechanism being tested.
NCT07598825 PHASE_III NOT_RECRUITING
MERCURY is a randomized, double-blind, placebo-controlled phase 2/3 program of the CD19-directed monoclonal antibody inebilizumab plus standard care in an estimated 180 AIH participants, assessing safety, disease activity, and glucocorticoid use.
Show evidence (1 reference)
clinicaltrials:NCT07598825 SUPPORT Other
"The main objectives of this trial are to evaluate the safety and tolerability of inebilizumab in participants with autoimmune hepatitis (AIH) (Part 1) and to evaluate the efficacy of inebilizumab on AIH disease activity and glucocorticoid (GC) use in the management of AIH (Part 2)."
The registry states the two-part safety and efficacy objectives.
NCT06250309 NOT_APPLICABLE RECRUITING
A 48-participant single-center crossover pilot compares Mediterranean and Western diets for fatigue and quality-of-life outcomes in AIH.
Target Phenotypes: Fatigue HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT06250309 SUPPORT Other
"This is a single-center, proof-of-concept pilot study which uses a cross-over design to compare two dietary interventions/treatments: Western Diet (WD) vs Mediterranean (MD) and impact on quality-of-life parameters in AIH."
The registry summary supports the crossover dietary design and patient-reported outcome focus.
NCT07118657 NOT_APPLICABLE RECRUITING
A 40-participant pediatric AIH study compares vegan and standard diets and measures 180-day biochemical remission, stool metagenomics/metabolomics, cytokines, barrier function, and liver-disease severity.
Show evidence (1 reference)
clinicaltrials:NCT07118657 SUPPORT Other
"In Aim 2, investigator will evaluate the proportion of patients achieving biochemical remission after 180 days of a vegan versus standard diet in AIH patients."
The registry directly states the randomized dietary comparison and biochemical-remission objective.
NCT06855667 NOT_APPLICABLE NOT_RECRUITING
A planned 50-participant pilot randomizes acute severe AIH to plasma exchange or steroid-based standard medical therapy and evaluates 28-day transplant-free survival and biochemical response.
Target Phenotypes: Acute hepatic failure HP:0006554 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Acute hepatic failure (HP:0006554). HP:0006554 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT06855667 SUPPORT Other
"The study aims at proving the efficacy of Plasma exchange as a bridge between steroid therapy and Liver transplant."
The registry states the investigational bridge-to-transplant rationale; this is an objective, not an efficacy result.
NCT05473403 NOT_APPLICABLE NOT_RECRUITING
A prospective 150-participant acute severe AIH study validates a day-3 prognostic score intended to distinguish corticosteroid responders from patients needing rapid liver-transplant evaluation.
Target Phenotypes: Acute hepatic failure HP:0006554 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Acute hepatic failure (HP:0006554). HP:0006554 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT05473403 SUPPORT Other
"The score will be computed at day 3 since corticosteroid introduction."
The registry summary states the timing of the prospective response score.
NCT06650124 PHASE_III NOT_RECRUITING
A planned phase 2/3, 108-participant comparison of MMF plus prednisolone versus azathioprine plus prednisolone in treatment-naive AIH, with 24-week biochemical remission and safety outcomes.
Show evidence (1 reference)
clinicaltrials:NCT06650124 SUPPORT Other
"The goal of this clinical trial is to determine the effectiveness of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH)."
The registry directly states the treatment-naive comparative objective.
{ }

Source YAML

click to show 
name: Autoimmune Hepatitis
creation_date: '2025-12-19T01:12:52Z'
category: Autoimmune
parents:
- Autoimmune Disease
- Liver Disease
synonyms:
- AIH
- autoimmune chronic active hepatitis
disease_term:
  preferred_term: Autoimmune Hepatitis
  term:
    id: MONDO:0016264
    label: autoimmune hepatitis
description: >-
  Autoimmune hepatitis (AIH) is an idiopathic immune-mediated necroinflammatory
  liver disease with a clinical spectrum from asymptomatic biochemical
  abnormalities to acute liver failure. Diagnosis requires clinicopathologic
  integration of serum aminotransferases, IgG, autoantibodies, liver histology,
  and exclusion of competing causes; no single finding is pathognomonic.
  Persistent untreated inflammation can lead to fibrosis, cirrhosis, and
  end-stage liver failure. ANA/SMA and anti-LKM1/LC1 patterns were historically
  called types 1 and 2, but current EASL guidance no longer recommends those
  serologic profiles as clinically distinct subtypes requiring different
  treatment strategies.
prevalence:
- population: Global pooled estimate from population-based studies
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 1.28
  rate_low: 1.01
  rate_high: 1.63
  notes: >-
    Annual incidence per 100,000 inhabitant-years. Between-study heterogeneity
    was extreme (I2 99.51%), so the pooled value is not a universal regional
    rate.
  evidence:
  - reference: PMID:37876996
    reference_title: "Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Global pooled incidence and prevalence of AIH were found to be 1.28 cases
      per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of
      studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000
      inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26;
      sample population, 217,178,684), respectively.
    explanation: >-
      The population-based meta-analysis supplies the pooled annual incidence,
      confidence interval, and heterogeneity used here.
- population: Global pooled estimate from population-based studies
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 15.65
  rate_low: 13.42
  rate_high: 18.24
  notes: >-
    Pooled prevalence per 100,000 inhabitants. The estimate combines markedly
    heterogeneous populations (I2 99.75%) and the authors found evidence of
    publication bias and substantial geographic variation.
  evidence:
  - reference: PMID:37876996
    reference_title: "Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Global pooled incidence and prevalence of AIH were found to be 1.28 cases
      per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of
      studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000
      inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26;
      sample population, 217,178,684), respectively.
    explanation: >-
      The meta-analysis supplies the pooled prevalence and confidence interval.
clinical_burden:
  burden_level: VARIABLE
  rationale: >-
    Burden varies from asymptomatic disease to acute liver failure. Even
    clinically stable disease commonly requires long-term immunosuppression and
    repeated specialist follow-up; delayed treatment can permit cirrhosis and
    end-stage liver failure. Quality-of-life and mental-health burden may remain
    clinically important even in ambulatory patients.
  evidence:
  - reference: PMID:40348684
    reference_title: EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At baseline, the clinical spectrum of the disease varies largely from
      asymptomatic cases to acute liver failure with massive hepatocyte necrosis.
    explanation: >-
      Current guidance directly supports the very broad severity spectrum.
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most patients need lifelong maintenance therapy, and repeated follow-up in
      experienced hands improves the quality of care and quality of life for
      affected patients.
    explanation: >-
      The review documents the chronic treatment and follow-up burden.
  - reference: PMID:24240053
    reference_title: Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Based on patient-reported data, a major depressive syndrome (10.8%) was
      found to be five times more frequent in AIH patients compared to the
      general population (p<0.001).
    explanation: >-
      A single-center outpatient cohort supports an additional psychosocial
      burden but is not assumed to represent all populations.
progression:
- phase: Asymptomatic or insidious presentation
  notes: >-
    Some patients are found through abnormal laboratory testing and do not pass
    through a fixed sequence of clinical stages.
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical presentation is often that of acute hepatitis, sometimes very
      severe; less frequently, it can be insidious or completely asymptomatic.
    explanation: >-
      The review directly identifies insidious and asymptomatic presentations.
- phase: Acute or acute-severe presentation
  notes: >-
    Acute hepatitis, including acute liver failure, can be the initial
    presentation rather than a late phase of previously recognized disease.
  evidence:
  - reference: PMID:40348684
    reference_title: EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At baseline, the clinical spectrum of the disease varies largely from
      asymptomatic cases to acute liver failure with massive hepatocyte necrosis.
    explanation: >-
      Current guidance identifies acute liver failure as part of the baseline
      spectrum.
- phase: Persistent inflammation with fibrosis and advanced liver disease
  notes: >-
    When diagnosis or effective treatment is delayed, chronic inflammation may
    progress to cirrhosis and end-stage liver failure. This is preventable in
    many patients and is not an inevitable stage.
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Autoimmune hepatitis is an inflammatory disease of the liver of unknown
      cause that may progress to liver cirrhosis and end stage liver failure if
      diagnosis is overlooked and treatment delayed.
    explanation: >-
      The review directly links delayed diagnosis and treatment to advanced
      liver disease.
pathophysiology:
- name: Polygenic HLA-linked susceptibility
  biological_scale: MOLECULAR
  mechanism_confidence: ESTABLISHED
  description: >-
    Common germline variation creates a polygenic susceptibility rather than a
    Mendelian cause. HLA-DRB1*03:01 and *04:01 are major signals in European
    type-1-serology cohorts, while HLA-B*35:01 is the strongest signal in a Han
    Chinese cohort; these ancestry-dependent associations implicate antigen
    presentation. SH2B3 adds a non-HLA immune-signaling susceptibility signal.
  genes:
  - preferred_term: HLA-DRB1
    term:
      id: hgnc:4948
      label: HLA-DRB1
  - preferred_term: HLA-B
    term:
      id: hgnc:4932
      label: HLA-B
  - preferred_term: SH2B3
    term:
      id: hgnc:29605
      label: SH2B3
  evidence:
  - reference: PMID:24768677
    reference_title: Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Analysis of this variant in the discovery cohort identified HLA-DRB1*0301
      (P = 5.3 × 10(-49)) as a primary susceptibility genotype and
      HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype.
    explanation: >-
      A replicated European GWAS identifies the two principal HLA-DRB1
      susceptibility alleles.
  - reference: PMID:38089552
    reference_title: Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Stepwise conditional analysis revealed the strongest allele was in the
      HLA-B gene (HLA-B*35:01, p = 8.17×10-304; OR = 7.32), with additional
      independent signals at HLA-B*08:01 (p = 1.35 × 10-33; OR = 4.26) and
      rs7765379 (p = 5.08 × 10-18; OR = 1.66).
    explanation: >-
      Fine mapping in 1,622 Chinese cases and matched controls establishes an
      ancestry-specific HLA-B susceptibility pattern.
  downstream:
  - target: Liver-autoantigen-specific adaptive immune activation
    description: >-
      Genetic susceptibility, together with incompletely defined triggers and
      tolerance failure, permits an adaptive response against liver
      autoantigens.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Environmental triggers are not defined for most patients.
    - The steps converting HLA-associated risk into loss of self-tolerance remain incompletely resolved.
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: PMID:29644994
      reference_title: Autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        AIH arises in genetically predisposed individuals when a trigger, such as
        exposure to a virus, leads to a T cell-mediated autoimmune response
        directed against liver autoantigens; this immune response is permitted by
        inadequate regulatory immune control leading to a loss of tolerance.
      explanation: >-
        The disease primer explicitly links genetic predisposition, a trigger,
        loss of tolerance, and liver-autoantigen-directed T-cell autoimmunity.
- name: Liver-autoantigen-specific adaptive immune activation
  biological_scale: CELLULAR
  mechanism_confidence: ESTABLISHED
  description: >-
    Autoreactive T and B cells recognize liver-associated self antigens. Human
    clonal analysis has directly demonstrated SepSecS/SLA-specific CD4 T cells
    and B cells, while also finding lower-level SepSecS-reactive T cells in
    controls; the response is therefore disease-associated but not by itself
    diagnostic or universally disease-specific.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  biological_processes:
  - preferred_term: adaptive immune response
    term:
      id: GO:0002250
      label: adaptive immune response
  - preferred_term: T cell activation
    term:
      id: GO:0042110
      label: T cell activation
  - preferred_term: B cell activation
    term:
      id: GO:0042113
      label: B cell activation
  evidence:
  - reference: PMID:39817450
    reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SepSecS-specific CD4+ T cell clones were found in patients with AIH who
      were anti-SLA-positive and anti-SLA-negative, and, to a lesser extent, in
      patients with non-AIH liver diseases and in healthy individuals.
    explanation: >-
      Human clonal analysis directly supports an autoantigen-specific CD4
      response while preserving its incomplete disease specificity.
  downstream:
  - target: Autoantibody and hyper-IgG response
    description: >-
      Cognate B-cell antigen presentation and T-cell help support affinity-matured
      autoantibody production and the polyclonal IgG response.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    - b_cell_amplification
    evidence:
    - reference: PMID:39817450
      reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        SepSecS-specific B cell clones, but not those of unrelated
        specificities, were able to present soluble SepSecS to specific T cells.
      explanation: >-
        The primary human study demonstrates antigen-specific B-cell
        presentation to cognate T cells.
  - target: T-cell-mediated hepatocyte injury
    description: >-
      The autoreactive response is modeled as driving hepatocyte injury through
      effector T-cell and cytokine pathways; the precise dominant cytotoxic
      subset and antigenic targets remain incompletely mapped in human liver.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: PMID:29644994
      reference_title: Autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        AIH arises in genetically predisposed individuals when a trigger, such as
        exposure to a virus, leads to a T cell-mediated autoimmune response
        directed against liver autoantigens
      explanation: >-
        The review supports T-cell-mediated liver-autoantigen autoimmunity but
        does not establish a single cytotoxic subset.
  - target: Arthralgia
    description: >-
      Joint pain is an extrahepatic symptom of AIH, but the intermediates linking
      liver-directed adaptive autoimmunity to arthralgia are not established.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
      reference_title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Overview of symptoms and causes of autoimmune hepatitis. Symptoms may
        include fatigue, joint pain, nausea, poor appetite, pain over your liver,
        and jaundice.
      explanation: >-
        The NIDDK clinical summary supports joint pain as a manifestation, while
        the mechanistic link remains uncertain.
- name: Autoantibody and hyper-IgG response
  biological_scale: CELLULAR
  mechanism_confidence: ESTABLISHED
  description: >-
    Activated B-cell and plasma-cell lineages generate elevated IgG and
    characteristic ANA, SMA, anti-LKM1/LC1, and anti-SLA/SepSecS antibodies.
    These are diagnostically useful outputs of adaptive immunity; this graph
    does not assume that circulating autoantibodies directly injure hepatocytes.
  cell_types:
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  - preferred_term: plasma cell
    term:
      id: CL:0000786
      label: plasma cell
  biological_processes:
  - preferred_term: immunoglobulin production
    term:
      id: GO:0002377
      label: immunoglobulin production
  evidence:
  - reference: PMID:39817450
    reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured
      compared with their germline versions, and recognized at least 3
      nonoverlapping epitopes.
    explanation: >-
      Human monoclonal antibodies directly demonstrate an affinity-matured IgG1
      response to an AIH autoantigen.
- name: T-cell-mediated hepatocyte injury
  biological_scale: CELLULAR
  mechanism_confidence: ESTABLISHED
  description: >-
    Liver-autoantigen-directed T-cell activation and inflammatory cytokine
    production promote hepatocyte injury and death. The prior record's claim
    that CD8 T cells recognize MHC class II on hepatocytes was removed: CD8
    restriction is to MHC class I, and the available AIH evidence does not
    establish that erroneous route.
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  biological_processes:
  - preferred_term: T cell mediated cytotoxicity
    term:
      id: GO:0001913
      label: T cell mediated cytotoxicity
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  evidence:
  - reference: PMID:39817450
    reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SepSecS-specific T cell clones from patients with AIH produced IFN-γ,
      IL-4, and IL-10, targeted multiple SepSecS epitopes, and, in one patient,
      were clonally expanded in both blood and liver biopsy.
    explanation: >-
      The study supports cytokine-producing autoantigen-specific T cells and
      liver expansion in one patient, but not a universal CD8 cytotoxic route.
  downstream:
  - target: Interface hepatitis and hepatocellular necroinflammation
    description: >-
      Persistent adaptive immune injury produces periportal/interface
      inflammation and hepatocyte necroinflammation.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: PMID:36746473
      reference_title: Diagnosis and management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        An abnormal immune response targeting liver autoantigens and inducing
        persistent and self-perpetuating liver inflammation is the pathogenic
        mechanism of the disease.
      explanation: >-
        The clinical review directly links liver-autoantigen immunity to
        persistent hepatic inflammation.
- name: Interface hepatitis and hepatocellular necroinflammation
  biological_scale: TISSUE
  mechanism_confidence: ESTABLISHED
  description: >-
    Immune-cell-rich interface hepatitis and periportal necroinflammation are
    the characteristic tissue injury pattern. Histology is central to diagnosis
    but is not independently pathognomonic.
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A specific set of autoantibodies, increased IgG concentrations, and
      histological demonstration of interface hepatitis and periportal necrosis
      are the diagnostic hallmarks of autoimmune hepatitis.
    explanation: >-
      The review directly identifies interface hepatitis and periportal
      necrosis as diagnostic tissue hallmarks.
  downstream:
  - target: Fatigue
    description: >-
      Systemic consequences of inflammatory liver disease can manifest as
      fatigue, although the responsible intermediates are not resolved.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
      reference_title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Overview of symptoms and causes of autoimmune hepatitis. Symptoms may
        include fatigue, joint pain, nausea, poor appetite, pain over your liver,
        and jaundice.
      explanation: >-
        The source supports fatigue as a symptom but does not resolve its causal
        intermediates.
  - target: Jaundice
    description: >-
      Hepatocellular dysfunction can impair bilirubin handling and produce
      jaundice.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Impaired hepatic bilirubin uptake, conjugation, or excretion
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
      reference_title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Overview of symptoms and causes of autoimmune hepatitis. Symptoms may
        include fatigue, joint pain, nausea, poor appetite, pain over your liver,
        and jaundice.
      explanation: >-
        The source supports jaundice as an AIH manifestation; the bilirubin
        intermediary is standard hepatic physiology.
  - target: Acute hepatic failure
    description: >-
      Severe, rapidly progressive hepatocyte necrosis can cause acute liver
      failure at presentation.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: PMID:40348684
      reference_title: EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        At baseline, the clinical spectrum of the disease varies largely from
        asymptomatic cases to acute liver failure with massive hepatocyte necrosis.
      explanation: >-
        Current guidance directly associates acute liver failure with massive
        hepatocyte necrosis in AIH.
  - target: Chronic hepatic fibrogenesis
    description: >-
      Persistent necroinflammation stimulates progressive hepatic matrix
      deposition; effective treatment can halt or reverse part of this process.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Hepatic stellate-cell activation
    - Excess extracellular-matrix deposition
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: PMID:36746473
      reference_title: Diagnosis and management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Treatment can often even reverse liver fibrosis, thus preventing
        progression to advanced cirrhosis and its complications.
      explanation: >-
        Reversibility with control of inflammation supports fibrosis as a
        downstream, modifiable consequence of active disease.
- name: Chronic hepatic fibrogenesis
  biological_scale: TISSUE
  mechanism_confidence: ESTABLISHED
  description: >-
    Recurrent or persistent inflammatory injury drives extracellular-matrix
    accumulation and architectural remodeling of the liver. Advanced fibrosis
    culminates in cirrhosis and its complications.
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  biological_processes:
  - preferred_term: extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Autoimmune hepatitis is an inflammatory disease of the liver of unknown
      cause that may progress to liver cirrhosis and end stage liver failure if
      diagnosis is overlooked and treatment delayed.
    explanation: >-
      The review supports progressive fibrotic architectural disease when
      inflammation remains untreated.
  downstream:
  - target: Cirrhosis
    description: >-
      Advanced fibrotic remodeling produces cirrhotic liver architecture.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_adaptive_autoimmunity
    evidence:
    - reference: PMID:36746473
      reference_title: Diagnosis and management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Treatment can often even reverse liver fibrosis, thus preventing
        progression to advanced cirrhosis and its complications.
      explanation: >-
        The review directly places advanced cirrhosis downstream of liver
        fibrosis.
mechanistic_hypotheses:
- hypothesis_group_id: canonical_adaptive_autoimmunity
  hypothesis_label: HLA-linked loss of tolerance and adaptive hepatocyte injury
  status: CANONICAL
  description: >-
    Polygenic susceptibility and incompletely defined triggers permit a
    liver-autoantigen-directed adaptive response that produces hepatocyte
    injury, interface hepatitis, and—when persistent—fibrosis and cirrhosis.
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      AIH arises in genetically predisposed individuals when a trigger, such as
      exposure to a virus, leads to a T cell-mediated autoimmune response
      directed against liver autoantigens; this immune response is permitted by
      inadequate regulatory immune control leading to a loss of tolerance.
    explanation: >-
      The disease primer states the canonical genetic-trigger-tolerance-adaptive
      immunity model.
- hypothesis_group_id: b_cell_amplification
  hypothesis_label: Antigen-specific B-cell amplification of adaptive autoimmunity
  status: EMERGING
  description: >-
    Autoreactive B cells may amplify AIH through cognate antigen presentation,
    cytokine interactions, and antibody production. Antigen-specific human
    clonal data support this route, but the direct pathogenic contribution of
    circulating autoantibodies and the clinical benefit of selective B-cell
    targeting remain unresolved.
  evidence:
  - reference: PMID:39817450
    reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SepSecS-specific B cell clones, but not those of unrelated
      specificities, were able to present soluble SepSecS to specific T cells.
    explanation: >-
      Primary human clonal data directly demonstrate cognate autoantigen
      presentation by B cells.
  - reference: PMID:31226726
    reference_title: The Contribution of B Cells in Autoimmune Liver Diseases.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Autoreactive B cells can promote autoimmunity through antigen presentation
      to autoreactive T cells, production of autoantibodies, generation of
      cytokines promoting T cell activation and differentiation, and inhibition
      of regulatory T cells and B cells.
    explanation: >-
      This review supplies plausible amplification routes but covers several
      autoimmune liver diseases and does not establish AIH-specific causality for
      every route.
phenotypes:
- name: Fatigue
  category: Systemic
  description: >-
    Tiredness is a recognized patient symptom; no frequency band is asserted
    because the reviewed sources do not provide a representative estimate.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
    reference_title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Overview of symptoms and causes of autoimmune hepatitis. Symptoms may
      include fatigue, joint pain, nausea, poor appetite, pain over your liver,
      and jaundice.
    explanation: >-
      The NIDDK clinical summary explicitly lists fatigue among AIH symptoms.
- name: Jaundice
  category: Hepatic
  description: >-
    Jaundice can accompany clinically apparent hepatitis or advanced liver
    dysfunction; its absence does not exclude AIH.
  phenotype_term:
    preferred_term: Jaundice
    term:
      id: HP:0000952
      label: Jaundice
  evidence:
  - reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
    reference_title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Overview of symptoms and causes of autoimmune hepatitis. Symptoms may
      include fatigue, joint pain, nausea, poor appetite, pain over your liver,
      and jaundice.
    explanation: >-
      The NIDDK clinical summary explicitly lists jaundice among AIH symptoms.
- name: Arthralgia
  category: Musculoskeletal
  description: >-
    Joint pain is a recognized extrahepatic symptom; no population frequency is
    inferred from the source.
  phenotype_term:
    preferred_term: Arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
  evidence:
  - reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
    reference_title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Overview of symptoms and causes of autoimmune hepatitis. Symptoms may
      include fatigue, joint pain, nausea, poor appetite, pain over your liver,
      and jaundice.
    explanation: >-
      The NIDDK clinical summary explicitly lists joint pain among AIH symptoms.
- name: Acute hepatic failure
  category: Hepatic
  severity: SEVERE
  description: >-
    Acute liver failure with massive hepatocyte necrosis is an uncommon but
    life-threatening possible presentation.
  phenotype_term:
    preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  evidence:
  - reference: PMID:40348684
    reference_title: EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At baseline, the clinical spectrum of the disease varies largely from
      asymptomatic cases to acute liver failure with massive hepatocyte necrosis.
    explanation: >-
      Current guidance directly identifies acute liver failure as an AIH
      presentation.
- name: Cirrhosis
  category: Hepatic
  severity: SEVERE
  description: >-
    Advanced fibrosis can progress to cirrhosis when active disease is missed or
    inadequately controlled.
  phenotype_term:
    preferred_term: Cirrhosis
    term:
      id: HP:0001394
      label: Cirrhosis
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Autoimmune hepatitis is an inflammatory disease of the liver of unknown
      cause that may progress to liver cirrhosis and end stage liver failure if
      diagnosis is overlooked and treatment delayed.
    explanation: >-
      The review directly supports cirrhosis as a preventable advanced outcome.
histopathology:
- name: Interface hepatitis with periportal necrosis
  diagnostic: true
  description: >-
    Liver biopsy typically shows interface hepatitis and periportal
    necroinflammation. These findings support AIH only in the appropriate
    clinical and serologic context and are not independently pathognomonic.
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A specific set of autoantibodies, increased IgG concentrations, and
      histological demonstration of interface hepatitis and periportal necrosis
      are the diagnostic hallmarks of autoimmune hepatitis.
    explanation: >-
      The review directly identifies the characteristic diagnostic histology.
biochemical:
- name: Antinuclear antibodies (ANA)
  presence: Positive
  context: Historical type-1 serologic pattern; not a current treatment-defining subtype
  specificity: Not specific for AIH
  readouts:
  - target: Autoantibody and hyper-IgG response
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: ANA positivity is a serologic readout of the adaptive autoantibody response, not proof of direct antibody-mediated hepatocyte injury.
    evidence:
    - reference: PMID:20862497
      reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In type 1 autoimmune hepatitis, the main circulating autoantibodies,
        although not specific for the disease, are antinuclear antibodies,
        smooth-muscle antibodies, and anti F-actin antibodies.
      explanation: >-
        The review supports ANA as a circulating diagnostic readout of the
        autoantibody response while explicitly noting incomplete specificity.
  evidence:
  - reference: PMID:20862497
    reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In type 1 autoimmune hepatitis, the main circulating autoantibodies,
      although not specific for the disease, are antinuclear antibodies,
      smooth-muscle antibodies, and anti F-actin antibodies.
    explanation: >-
      The review identifies ANA and explicitly notes incomplete specificity.
- name: Smooth-muscle and F-actin antibodies (SMA)
  presence: Positive
  context: Historical type-1 serologic pattern; not a current treatment-defining subtype
  specificity: Not specific for AIH
  readouts:
  - target: Autoantibody and hyper-IgG response
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: SMA/F-actin positivity reports the adaptive autoantibody response.
    evidence:
    - reference: PMID:20862497
      reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In type 1 autoimmune hepatitis, the main circulating autoantibodies,
        although not specific for the disease, are antinuclear antibodies,
        smooth-muscle antibodies, and anti F-actin antibodies.
      explanation: >-
        The review supports SMA and anti-F-actin as circulating diagnostic
        readouts of the autoantibody response.
  evidence:
  - reference: PMID:20862497
    reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In type 1 autoimmune hepatitis, the main circulating autoantibodies,
      although not specific for the disease, are antinuclear antibodies,
      smooth-muscle antibodies, and anti F-actin antibodies.
    explanation: >-
      The review identifies SMA/F-actin antibodies and explicitly notes
      incomplete specificity.
- name: Anti-LKM1 and anti-LC1 antibodies
  presence: Positive
  context: Historical type-2 serologic pattern; not a current treatment-defining subtype
  readouts:
  - target: Autoantibody and hyper-IgG response
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Anti-LKM1/LC1 positivity reports a recognized AIH serologic pattern.
    evidence:
    - reference: PMID:20862497
      reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In type 2 autoimmune hepatitis, a disease which occurs predominantly in
        girls and young women, anti-liver-kidney microsomal-1 antibodies and
        anti-cytosol-1 antibodies are the major circulating autoantibodies.
      explanation: >-
        The review supports anti-LKM1 and anti-LC1 as circulating diagnostic
        readouts of a recognized AIH serologic pattern.
  evidence:
  - reference: PMID:20862497
    reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In type 2 autoimmune hepatitis, a disease which occurs predominantly in
      girls and young women, anti-liver-kidney microsomal-1 antibodies and
      anti-cytosol-1 antibodies are the major circulating autoantibodies.
    explanation: >-
      The review identifies anti-LKM1 and anti-LC1 as the historical type-2
      serologic pattern.
- name: Anti-SLA/SepSecS antibodies
  presence: Positive
  context: Autoantibody directed against soluble liver antigen/SepSecS
  readouts:
  - target: Autoantibody and hyper-IgG response
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Anti-SLA/SepSecS positivity reports an affinity-matured autoantigen-specific B-cell response.
    evidence:
    - reference: PMID:39817450
      reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured
        compared with their germline versions, and recognized at least 3
        nonoverlapping epitopes.
      explanation: >-
        The primary human study supports anti-SLA/SepSecS as a readout of an
        affinity-matured, autoantigen-specific B-cell response.
  evidence:
  - reference: PMID:39817450
    reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured
      compared with their germline versions, and recognized at least 3
      nonoverlapping epitopes.
    explanation: >-
      The primary human study directly characterizes affinity-matured
      anti-SepSecS antibodies.
- name: Serum immunoglobulin G (IgG)
  presence: Elevated
  context: Diagnostic and treatment-response biomarker; a normal value does not by itself exclude AIH
  readouts:
  - target: Autoantibody and hyper-IgG response
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Increased serum IgG reports the humoral immune response and is used with other diagnostic findings.
    evidence:
    - reference: PMID:29644994
      reference_title: Autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The diagnosis of AIH relies on increased serum transaminase and
        immunoglobulin G levels, presence of autoantibodies and interface
        hepatitis on liver histology.
      explanation: >-
        The disease primer directly supports increased serum IgG as a
        diagnostic readout used with serology and histology.
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis of AIH relies on increased serum transaminase and
      immunoglobulin G levels, presence of autoantibodies and interface hepatitis
      on liver histology.
    explanation: >-
      The disease primer identifies increased IgG as a core diagnostic feature.
- name: Serum ALT and AST
  presence: Elevated
  context: Hepatocellular injury and biochemical-response biomarker
  readouts:
  - target: Interface hepatitis and hepatocellular necroinflammation
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: MONITORING
    interpretation: Elevated aminotransferases report active hepatocellular injury but are not specific to AIH.
    evidence:
    - reference: PMID:29644994
      reference_title: Autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The diagnosis of AIH relies on increased serum transaminase and
        immunoglobulin G levels, presence of autoantibodies and interface
        hepatitis on liver histology.
      explanation: >-
        The disease primer directly supports increased serum transaminases as a
        biochemical readout of active liver injury in the diagnostic context.
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis of AIH relies on increased serum transaminase and
      immunoglobulin G levels, presence of autoantibodies and interface hepatitis
      on liver histology.
    explanation: >-
      The disease primer identifies increased serum transaminases as a core
      diagnostic feature.
genetic:
- name: HLA-DRB1 susceptibility alleles
  gene_term:
    preferred_term: HLA-DRB1
    term:
      id: hgnc:4948
      label: HLA-DRB1
  association: HLA-DRB1*03:01 primary and HLA-DRB1*04:01 secondary susceptibility in replicated European type-1-serology cohorts
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE
  notes: >-
    This is an ancestry- and cohort-dependent risk association, not a diagnostic
    genotype or a monogenic cause.
  evidence:
  - reference: PMID:24768677
    reference_title: Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Analysis of this variant in the discovery cohort identified HLA-DRB1*0301
      (P = 5.3 × 10(-49)) as a primary susceptibility genotype and
      HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype.
    explanation: >-
      The discovery and replication study supports the two European-cohort
      HLA-DRB1 susceptibility alleles.
- name: HLA-B susceptibility alleles
  gene_term:
    preferred_term: HLA-B
    term:
      id: hgnc:4932
      label: HLA-B
  association: HLA-B*35:01 and additional independent HLA-B signals in a Han Chinese type-1-serology cohort
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE
  notes: >-
    The large effect estimate is specific to the studied Chinese cohort and
    should not be generalized across ancestries.
  evidence:
  - reference: PMID:38089552
    reference_title: Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Stepwise conditional analysis revealed the strongest allele was in the
      HLA-B gene (HLA-B*35:01, p = 8.17×10-304; OR = 7.32), with additional
      independent signals at HLA-B*08:01 (p = 1.35 × 10-33; OR = 4.26) and
      rs7765379 (p = 5.08 × 10-18; OR = 1.66).
    explanation: >-
      The 15-center Chinese fine-mapping study directly supports the
      HLA-B*35:01 association and additional independent signals.
- name: SH2B3 susceptibility variant
  gene_term:
    preferred_term: SH2B3
    term:
      id: hgnc:29605
      label: SH2B3
  association: Non-HLA common-variant susceptibility signal (rs3184504) in a European GWAS
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE
  notes: >-
    This is one component of complex polygenic susceptibility and is not a
    disease-causing Mendelian variant.
  evidence:
  - reference: PMID:24768677
    reference_title: Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 ×
      10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)).
    explanation: >-
      The GWAS directly supports SH2B3 as a non-HLA susceptibility locus.
treatments:
- name: Prednisone or prednisolone-based corticosteroid induction
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Systemic prednisone or prednisolone is used to induce remission, with dose
    and taper individualized to severity, response, and toxicity. Budesonide is
    deliberately not grouped into this current first-line entry; its older
    noncirrhotic trial and the 2025 guideline reversal are documented below.
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
  target_mechanisms:
  - target: T-cell-mediated hepatocyte injury
    treatment_effect: INHIBITS
    description: Broad glucocorticoid immunosuppression reduces immune-mediated hepatocyte injury.
    evidence:
    - reference: PMID:29644994
      reference_title: Autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Standard regimens include fairly high initial doses of corticosteroids
        (prednisone or prednisolone), which are tapered gradually as
        azathioprine is introduced.
      explanation: >-
        Clinical use of corticosteroid induction supports suppression of the
        autoimmune-injury pathway, but this passage does not isolate a
        T-cell-specific pharmacodynamic effect.
  - target: Interface hepatitis and hepatocellular necroinflammation
    treatment_effect: INHIBITS
    description: Suppression of active inflammation is the induction target.
    evidence:
    - reference: PMID:36746473
      reference_title: Diagnosis and management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The aims of treatment are to induce and maintain long term remission of
        liver inflammation.
      explanation: >-
        The review directly identifies remission of liver inflammation as the
        treatment target.
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Standard regimens include fairly high initial doses of corticosteroids
      (prednisone or prednisolone), which are tapered gradually as azathioprine
      is introduced.
    explanation: >-
      The disease primer directly supports prednisone/prednisolone induction and
      tapering.
- name: Azathioprine steroid-sparing therapy
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Azathioprine is introduced as a steroid-sparing agent for maintenance or as
    part of combination induction, with patient-specific contraindication and
    toxicity assessment.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
  target_mechanisms:
  - target: Liver-autoantigen-specific adaptive immune activation
    treatment_effect: INHIBITS
    description: Antimetabolite immunosuppression reduces lymphocyte proliferation and supports steroid sparing.
    evidence:
    - reference: PMID:29644994
      reference_title: Autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Standard regimens include fairly high initial doses of corticosteroids
        (prednisone or prednisolone), which are tapered gradually as
        azathioprine is introduced.
      explanation: >-
        The standard steroid-sparing regimen supports modulation of the
        adaptive autoimmune pathway, although this passage does not directly
        measure lymphocyte proliferation.
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Standard regimens include fairly high initial doses of corticosteroids
      (prednisone or prednisolone), which are tapered gradually as azathioprine
      is introduced.
    explanation: >-
      The review directly supports azathioprine as the steroid-sparing standard
      agent.
- name: Mycophenolate mofetil immunosuppression
  action_category: THERAPEUTIC
  therapeutic_modality: SMALL_MOLECULE
  description: >-
    Mycophenolate mofetil (MMF) is a current first-line alternative to
    azathioprine and remains an option for intolerance or inadequate response.
    It is teratogenic and requires reproductive-risk counseling. The strongest
    direct comparison is a small 24-week, open-label adult trial, so long-term
    and broader-population comparative effectiveness remains less certain.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: mycophenolate mofetil
      term:
        id: CHEBI:8764
        label: mycophenolate mofetil
  target_mechanisms:
  - target: Liver-autoantigen-specific adaptive immune activation
    treatment_effect: INHIBITS
    description: MMF suppresses lymphocyte proliferation and the adaptive autoimmune response.
    evidence:
    - reference: PMID:38101756
      reference_title: An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The primary endpoint was met in 56.4% and 29.0% of patients assigned to
        the MMF group and the azathioprine group, respectively (difference, 27.4
        percentage points; 95% CI 4.0 to 46.7; p = 0.022).
      explanation: >-
        The randomized comparison supports clinical pathway modulation by MMF,
        but it does not directly measure the proposed lymphocyte-level target.
  evidence:
  - reference: PMID:38101756
    reference_title: An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The primary endpoint was met in 56.4% and 29.0% of patients assigned to the
      MMF group and the azathioprine group, respectively (difference, 27.4
      percentage points; 95% CI 4.0 to 46.7; p = 0.022).
    explanation: >-
      The randomized comparison supports higher 24-week biochemical remission
      with MMF plus prednisolone in this 70-patient open-label cohort.
  - reference: "url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/"
    reference_title: "New EASL Clinical Practice Guidelines on the management of Autoimmune Hepatitis - EASL-The Home of Hepatology."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Therapeutically, the updated guidelines introduce Mycophenolate mofetil as
      a viable and safe first-line alternative to azathioprine. It is now
      recognised for its comparable or even superior efficacy and reduced rate
      of adverse events. However, clinicians are cautioned about its teratogenic
      risks, particularly in patients of reproductive age.
    explanation: >-
      The official EASL summary supports MMF as a first-line alternative and
      states the reproductive-safety caveat.
- name: Liver transplantation
  action_category: THERAPEUTIC
  therapeutic_modality: SURGERY
  description: >-
    Liver transplantation is a rescue treatment for acute liver failure or
    decompensated end-stage disease when medical therapy cannot restore adequate
    function. AIH may recur after transplantation.
  treatment_term:
    preferred_term: liver transplantation
    term:
      id: NCIT:C15271
      label: Liver Transplantation
  target_phenotypes:
  - preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  - preferred_term: Cirrhosis
    term:
      id: HP:0001394
      label: Cirrhosis
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Liver transplantation is a life-saving option for those who progress to
      end-stage liver disease, although AIH can recur or develop de novo after
      transplantation.
    explanation: >-
      The primer supports transplantation for end-stage disease and the risk of
      post-transplant recurrence.
diagnosis:
- name: Integrated serum biochemistry and autoantibody evaluation
  diagnosis_term:
    preferred_term: clinical laboratory procedure
    term:
      id: NCIT:C25294
      label: Laboratory Procedure
  description: >-
    Measure serum ALT/AST and IgG and test an appropriate autoantibody panel
    (including ANA, SMA/F-actin, anti-LKM1/LC1, and anti-SLA when indicated).
    Results must be integrated with histology and competing-cause evaluation;
    neither seronegativity nor a normal IgG alone is modeled as exclusionary.
  results: A compatible hepatocellular injury pattern, increased IgG, and characteristic autoantibodies support but do not independently establish AIH.
  evidence:
  - reference: PMID:29644994
    reference_title: Autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis of AIH relies on increased serum transaminase and
      immunoglobulin G levels, presence of autoantibodies and interface hepatitis
      on liver histology.
    explanation: >-
      The disease primer directly supports the integrated biochemical,
      serologic, and histologic diagnostic pattern.
- name: Liver biopsy with histopathologic assessment
  diagnosis_term:
    preferred_term: biopsy of liver
    term:
      id: NCIT:C51677
      label: Liver Biopsy
  description: >-
    Liver biopsy assesses interface activity, periportal necrosis, fibrosis, and
    competing patterns. It remains a diagnostic cornerstone rather than a
    standalone disease-specific test.
  results: Interface hepatitis and periportal necroinflammation support AIH in the appropriate clinic-serologic context.
  evidence:
  - reference: PMID:36746473
    reference_title: Diagnosis and management of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A specific set of autoantibodies, increased IgG concentrations, and
      histological demonstration of interface hepatitis and periportal necrosis
      are the diagnostic hallmarks of autoimmune hepatitis.
    explanation: >-
      The clinical review directly supports the biopsy pattern within an
      integrated diagnosis.
  - reference: "url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/"
    reference_title: "New EASL Clinical Practice Guidelines on the management of Autoimmune Hepatitis - EASL-The Home of Hepatology."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      These new standards are designed to support more consistent and
      standardised interpretation of liver biopsies, which remain a cornerstone
      of AIH diagnosis.
    explanation: >-
      The official 2025 EASL summary explicitly retains liver biopsy as a
      diagnostic cornerstone.
- name: Simplified International Autoimmune Hepatitis Group score
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: NCIT:C124351
      label: Clinical Evaluation
  description: >-
    The simplified score combines autoantibodies, IgG, histology, and exclusion
    of viral hepatitis. A score of at least 6 supports probable AIH and at least
    7 supports definite AIH; it supports clinical reasoning but does not replace
    expert assessment in atypical or acute-severe presentations.
  results: In the original validation set, cutoff 6 had 88% sensitivity and 97% specificity; cutoff 7 had 81% sensitivity and 99% specificity.
  evidence:
  - reference: PMID:18537184
    reference_title: Simplified criteria for the diagnosis of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This score included autoantibodies, immunoglobulin G, histology, and
      exclusion of viral hepatitis.
    explanation: >-
      The primary criteria study defines the four score components.
  - reference: PMID:18537184
    reference_title: Simplified criteria for the diagnosis of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The score was found to have 88% sensitivity and 97% specificity (cutoff >
      or =6) and 81% sensitivity and 99% specificity (cutoff > or =7) in the
      validation set.
    explanation: >-
      The primary validation supplies the cutoff performance characteristics.
differential_diagnoses:
- name: Viral hepatitis
  description: >-
    Acute or chronic viral hepatitis can produce the same hepatocellular enzyme
    pattern and overlapping histology. Virologic testing and exposure context
    are required before assigning idiopathic AIH.
  distinguishing_features:
  - Positive pathogen-specific nucleic-acid or serologic evidence
  - Epidemiologic exposure context
  - Simplified AIH criteria explicitly require exclusion of viral hepatitis
  evidence:
  - reference: PMID:18537184
    reference_title: Simplified criteria for the diagnosis of autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This score included autoantibodies, immunoglobulin G, histology, and
      exclusion of viral hepatitis.
    explanation: >-
      The validated diagnostic score explicitly requires viral-hepatitis
      exclusion.
- name: Drug-induced autoimmune-like hepatitis
  description: >-
    Drug-induced liver injury may reproduce autoantibodies, increased IgG, and
    an autoimmune-like histologic pattern. The idiopathic AIH disease boundary
    used here excludes cases attributed to a drug or herb after temporal and
    causality assessment.
  distinguishing_features:
  - Compatible medication or supplement exposure and latency
  - Improvement after withdrawal may support drug causality
  - Relapse behavior after immunosuppression withdrawal may differ, but is not by itself definitive
  evidence:
  - reference: PMID:25574080
    reference_title: "Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      AIH should be considered in every case in the absence of viral, metabolic,
      genetic and toxic etiology of chronic or acute hepatitis.
    explanation: >-
      The review explicitly requires exclusion of toxic causes, supporting the
      drug-induced boundary without supplying a complete causality algorithm.
- name: Wilson disease
  disease_term:
    preferred_term: Wilson disease
    term:
      id: MONDO:0010200
      label: Wilson disease
  description: >-
    Wilson disease can present as acute hepatitis, chronic hepatitis, or liver
    failure and must be excluded in compatible age groups and presentations.
  distinguishing_features:
  - Copper studies and ATP7B evaluation support Wilson disease
  - Kayser-Fleischer rings or neurologic features may be present but are not required
  - Autoantibody positivity does not independently exclude Wilson disease
  evidence:
  - reference: PMID:25574080
    reference_title: "Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      AIH should be considered in every case in the absence of viral, metabolic,
      genetic and toxic etiology of chronic or acute hepatitis.
    explanation: >-
      The review requires exclusion of metabolic and genetic causes; Wilson
      disease is a key such mimic.
- name: Primary biliary cholangitis, primary sclerosing cholangitis, and AIH variant syndromes
  description: >-
    Cholestatic biochemistry, bile-duct injury, cholangiography, and
    disease-specific serology may identify PBC, PSC, or an AIH variant syndrome.
    Variant/overlap taxonomy remains controversial and should not be treated as
    a simple autoantibody-defined AIH subtype.
  distinguishing_features:
  - Antimitochondrial antibodies and small-duct cholangitis support PBC
  - Multifocal biliary stricturing and inflammatory bowel disease support PSC
  - Combined hepatitic and cholangiopathic findings may support a variant syndrome
  evidence:
  - reference: PMID:20862497
    reference_title: Discrimination of autoimmune hepatitis—autoantibody typing and beyond.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      There also are patients with variant forms of autoimmune hepatitis who
      have clinical and serologic findings of autoimmune hepatitis in addition
      to features of primary biliary cirrhosis or primary sclerosing cholangitis.
      The taxonomy and definitions of these variants, often referred to as
      overlap syndromes, are controversial.
    explanation: >-
      The review supports the combined-feature variants and explicitly notes
      taxonomic uncertainty.
- name: Immune checkpoint inhibitor-associated hepatitis
  description: >-
    Immune-mediated hepatitis after checkpoint blockade is a treatment-related
    immune adverse event, not idiopathic AIH, even though T-cell activation,
    transaminase elevation, and steroid responsiveness may overlap.
  distinguishing_features:
  - Temporal relationship to immune checkpoint inhibitor exposure
  - Diagnosis of exclusion within an oncology treatment context
  - Histology and serology may differ from idiopathic AIH
  evidence:
  - reference: DOI:10.3389/fphar.2022.1077468
    reference_title: "Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Because of the lack of specific markers, a diagnosis of exclusion of IMH
      is critical.
    explanation: >-
      The review supports checkpoint-inhibitor hepatitis as a diagnosis of
      exclusion defined by treatment exposure.
datasets:
- accession: geo:GSE216064
  title: scRNA-seq for analyzing the characteristics of PBMC in patients with autoimmune hepatitis
  description: >-
    Human peripheral-blood single-cell RNA-sequencing dataset comparing pooled
    PBMCs from four AIH patients with pooled PBMCs from four healthy controls.
  organism:
    preferred_term: Homo sapiens
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_types:
  - preferred_term: peripheral blood mononuclear cells
    term:
      id: UBERON:0000178
      label: blood
    cell_type_term:
      preferred_term: peripheral blood mononuclear cell
      term:
        id: CL:0000842
        label: mononuclear leukocyte
    tissue_term:
      preferred_term: blood
      term:
        id: UBERON:0000178
        label: blood
  sample_count: 2
  conditions:
  - pooled PBMCs from four autoimmune hepatitis patients
  - pooled PBMCs from four healthy controls
  platform: 10x Genomics Chromium 3' gene expression v2
  publication: PMID:38340154
  notes: >-
    GEO contains two pooled assay libraries, not eight independent libraries.
    The eight biological donors were pooled into one AIH and one control
    library, preventing donor-level estimation and leaving liver-tissue
    causality unresolved. The publication reports 3,511 AIH and 3,690 control
    cell transcriptomes.
  evidence:
  - reference: GEO:GSE216064
    reference_title: scRNA-seq for analyzing the characteristics of PBMC in patients with autoimmune hepatitis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      This present study was designed to analyze the characteristics of AIH
      peripheral blood mononuclear cells (PBMCs) through single-cell RNA
      sequencing (scRNA-seq, 10x Genomics Gene Expression 3' Chromium V 2.0) and
      to explore the potential molecular mechanism of AIH.
    explanation: >-
      GEO metadata directly supports the disease, sample type, and assay.
  - reference: PMID:38340154
    reference_title: "Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from
      4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq.
    explanation: >-
      The publication defines the donor pools and cell-transcriptome counts.
clinical_trials:
- name: NCT02997878
  phase: PHASE_II
  status: ACTIVE_NOT_RECRUITING
  description: >-
    MERLIN is an adaptive phase I/IIa, single-arm trial of one infusion of
    umbilical-cord-derived ORBCEL-C mesenchymal stromal cells. It enrolls PSC and
    AIH in distinct cohorts and includes AIH-specific ALT/IgG activity outcomes;
    18 participants were enrolled overall.
  notes: >-
    Registry status was active, not recruiting on 2026-07-21, but status was
    last verified in July 2024 and the estimated completion date was October
    2025. Included because a distinct AIH cohort exists; no efficacy is inferred.
  evidence:
  - reference: clinicaltrials:NCT02997878
    reference_title: An Adaptive, Multicentre, Phase IIa, Multi-disease Trial Investigating the Safety & Activity of a Single Infusion of Selected Mesenchymal Stromal Cells in the Treatment of Patients With Primary Sclerosing Cholangitis & Autoimmune Hepatitis
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MERLIN is an adaptive, single arm, multi-centre, phase IIa multi-disease
      clinical trial.
    explanation: >-
      The registry summary supports the adaptive early-phase multi-disease
      design.
- name: NCT06381453
  phase: PHASE_II
  status: RECRUITING
  description: >-
    BELief is an open-label multicenter study adding weekly belimumab, a
    monoclonal antibody that inhibits BAFF, to standard care in 48 adults with active
    disease or treatment-dependent remission. It tests steroid burden,
    biochemical control, safety, and exploratory immune biomarkers.
  notes: Recruiting as of the fully paginated registry audit on 2026-07-21; no efficacy result is asserted.
  evidence:
  - reference: clinicaltrials:NCT06381453
    reference_title: "Belimumab in the Management of Autoimmune Hepatitis: A Multi-centre, Open-label Trial of add-on Belimumab Therapy to Standard of Care"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Belimumab is a human monoclonal antibody that inhibits B-cell activating
      factor (BAFF), also known as B-lymphocyte stimulator.
    explanation: >-
      The registry states the intervention and B-cell-targeting mechanism being
      tested.
- name: NCT07598825
  phase: PHASE_III
  status: NOT_RECRUITING
  description: >-
    MERCURY is a randomized, double-blind, placebo-controlled phase 2/3 program
    of the CD19-directed monoclonal antibody inebilizumab plus standard care in
    an estimated 180 AIH participants, assessing safety, disease activity, and
    glucocorticoid use.
  notes: >-
    ClinicalTrials.gov reported NOT_YET_RECRUITING on 2026-07-21. The schema's
    NOT_RECRUITING value is used with the exact registry status preserved here;
    no efficacy is inferred.
  evidence:
  - reference: clinicaltrials:NCT07598825
    reference_title: "A Phase 2/3, Randomized, Double-blind, Multicenter, Placebo-controlled Study of Inebilizumab in Participants With Autoimmune Hepatitis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The main objectives of this trial are to evaluate the safety and
      tolerability of inebilizumab in participants with autoimmune hepatitis
      (AIH) (Part 1) and to evaluate the efficacy of inebilizumab on AIH disease
      activity and glucocorticoid (GC) use in the management of AIH (Part 2).
    explanation: >-
      The registry states the two-part safety and efficacy objectives.
- name: NCT06250309
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    A 48-participant single-center crossover pilot compares Mediterranean and
    Western diets for fatigue and quality-of-life outcomes in AIH.
  target_phenotypes:
  - preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  notes: Recruiting as of the fully paginated registry audit on 2026-07-21; proof-of-concept design, not established dietary therapy.
  evidence:
  - reference: clinicaltrials:NCT06250309
    reference_title: Randomized Crossover Diet Study Comparing Impact of Mediterranean Diet to Western Diet on Fatigue in Autoimmune Hepatitis Patients
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      This is a single-center, proof-of-concept pilot study which uses a
      cross-over design to compare two dietary interventions/treatments: Western
      Diet (WD) vs Mediterranean (MD) and impact on quality-of-life parameters in
      AIH.
    explanation: >-
      The registry summary supports the crossover dietary design and
      patient-reported outcome focus.
- name: NCT07118657
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    A 40-participant pediatric AIH study compares vegan and standard diets and
    measures 180-day biochemical remission, stool metagenomics/metabolomics,
    cytokines, barrier function, and liver-disease severity.
  notes: Recruiting and status verified in June 2026; complementary dietary study, not evidence to replace immunosuppression.
  evidence:
  - reference: clinicaltrials:NCT07118657
    reference_title: Host-Diet-Gut Interaction Post Vegan Diet in Pediatric Autoimmune Hepatitis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In Aim 2, investigator will evaluate the proportion of patients achieving
      biochemical remission after 180 days of a vegan versus standard diet in
      AIH patients.
    explanation: >-
      The registry directly states the randomized dietary comparison and
      biochemical-remission objective.
- name: NCT06855667
  phase: NOT_APPLICABLE
  status: NOT_RECRUITING
  description: >-
    A planned 50-participant pilot randomizes acute severe AIH to plasma exchange
    or steroid-based standard medical therapy and evaluates 28-day
    transplant-free survival and biochemical response.
  target_phenotypes:
  - preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  notes: >-
    ClinicalTrials.gov reported NOT_YET_RECRUITING on 2026-07-21, last verified
    February 2025 despite an estimated March 2025 start. The schema's
    NOT_RECRUITING value is used and no efficacy is inferred.
  evidence:
  - reference: clinicaltrials:NCT06855667
    reference_title: "Efficacy and Safety of Therapeutic Plasma Exchange vs Standard Medical Therapy in Severe Autoimmune Hepatitis: A Pilot Randomized Controlled Study"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The study aims at proving the efficacy of Plasma exchange as a bridge
      between steroid therapy and Liver transplant.
    explanation: >-
      The registry states the investigational bridge-to-transplant rationale;
      this is an objective, not an efficacy result.
- name: NCT05473403
  phase: NOT_APPLICABLE
  status: NOT_RECRUITING
  description: >-
    A prospective 150-participant acute severe AIH study validates a day-3
    prognostic score intended to distinguish corticosteroid responders from
    patients needing rapid liver-transplant evaluation.
  target_phenotypes:
  - preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  notes: >-
    ClinicalTrials.gov reported NOT_YET_RECRUITING on 2026-07-21, with status
    last verified September 2023 despite an estimated June 2024 start. The
    schema's NOT_RECRUITING value is used; registry staleness is material.
  evidence:
  - reference: clinicaltrials:NCT05473403
    reference_title: Validation of a Prognostic Score for Steroid Therapy Response in Acute Severe Autoimmune Hepatitis, a National Prospective Multicentre Study
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The score will be computed at day 3 since corticosteroid introduction.
    explanation: >-
      The registry summary states the timing of the prospective response score.
- name: NCT06650124
  phase: PHASE_III
  status: NOT_RECRUITING
  description: >-
    A planned phase 2/3, 108-participant comparison of MMF plus prednisolone
    versus azathioprine plus prednisolone in treatment-naive AIH, with 24-week
    biochemical remission and safety outcomes.
  notes: >-
    ClinicalTrials.gov reported NOT_YET_RECRUITING on 2026-07-21, last verified
    October 2024 despite an estimated December 2025 completion. The schema's
    NOT_RECRUITING value is used; this apparently stale record is retained but
    not treated as evidence of ongoing enrollment or efficacy.
  evidence:
  - reference: clinicaltrials:NCT06650124
    reference_title: Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The goal of this clinical trial is to determine the effectiveness of
      azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission
      in treatment-naive patients with autoimmune hepatitis (AIH).
    explanation: >-
      The registry directly states the treatment-naive comparative objective.
discussions:
- discussion_id: gap_b_cell_targeting_clinical_benefit
  prompt: >-
    Does selective BAFF or CD19-directed B-cell therapy safely improve durable
    biochemical control and reduce glucocorticoid exposure in AIH?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Autoantibody and hyper-IgG response
  - pathophysiology#Liver-autoantigen-specific adaptive immune activation
  rationale: >-
    Antigen-specific B-cell presentation is demonstrated in human samples, but
    direct antibody pathogenicity and clinical benefit from B-cell targeting
    remain unproven. BELief and MERCURY are testing two distinct B-cell-directed
    strategies; registry protocols must not be interpreted as positive results.
  evidence:
  - reference: PMID:39817450
    reference_title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SepSecS-specific B cell clones, but not those of unrelated
      specificities, were able to present soluble SepSecS to specific T cells.
    explanation: >-
      Human clonal data establish the biologic rationale for testing B-cell
      targeting.
  - reference: clinicaltrials:NCT06381453
    reference_title: "Belimumab in the Management of Autoimmune Hepatitis: A Multi-centre, Open-label Trial of add-on Belimumab Therapy to Standard of Care"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Belimumab is a human monoclonal antibody that inhibits B-cell activating
      factor (BAFF), also known as B-lymphocyte stimulator.
    explanation: >-
      The ongoing protocol tests BAFF inhibition but provides no efficacy result.
  - reference: clinicaltrials:NCT07598825
    reference_title: "A Phase 2/3, Randomized, Double-blind, Multicenter, Placebo-controlled Study of Inebilizumab in Participants With Autoimmune Hepatitis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The main objectives of this trial are to evaluate the safety and
      tolerability of inebilizumab in participants with autoimmune hepatitis
      (AIH) (Part 1) and to evaluate the efficacy of inebilizumab on AIH disease
      activity and glucocorticoid (GC) use in the management of AIH (Part 2).
    explanation: >-
      The ongoing protocol defines the CD19-directed question without supplying
      an answer.
- discussion_id: gap_paired_liver_blood_single_cell_resolution
  prompt: >-
    Which immune states are reproducibly enriched in AIH liver tissue, and how
    do they relate to matched blood, disease activity, ancestry, and treatment
    response at donor level?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Liver-autoantigen-specific adaptive immune activation
  - pathophysiology#T-cell-mediated hepatocyte injury
  rationale: >-
    The public AIH single-cell dataset pools four donors per condition into two
    PBMC libraries. It cannot estimate donor heterogeneity and samples blood,
    not the injured liver. A multi-ancestry longitudinal study with paired
    liver and blood single-cell/spatial profiling is needed before peripheral
    monocyte or NK signatures are promoted to causal liver mechanisms.
  evidence:
  - reference: PMID:38340154
    reference_title: "Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from
      4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq.
    explanation: >-
      The publication directly establishes the pooled peripheral design that
      creates the inference gap.
- discussion_id: interpretation_budesonide_guideline_reversal
  prompt: >-
    Should budesonide remain represented as a current first-line corticosteroid
    option for AIH?
  kind: INTERPRETATION
  status: RESOLVED
  attaches_to:
  - treatments#Prednisone or prednisolone-based corticosteroid induction
  rationale: >-
    A 2010 randomized trial favored budesonide plus azathioprine in patients
    explicitly selected to have no cirrhosis, but the official 2025 EASL update
    no longer endorses budesonide because of safety and effectiveness concerns.
    Current representation must follow the newer guidance while preserving the
    historical trial boundary.
  resolved_date: '2026-07-21T00:00:00Z'
  resolution_note: >-
    Budesonide was removed from the current first-line treatment description;
    prednisone/prednisolone remain represented, and the older noncirrhotic trial
    is retained here for provenance.
  evidence:
  - reference: PMID:20600032
    reference_title: Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We performed a 6-month, prospective, double-blind, randomized,
      active-controlled, multicenter, phase IIb trial of patients with AIH
      without evidence of cirrhosis who were given budesonide (3 mg, three times
      daily or twice daily) or prednisone (40 mg/d, tapered to 10 mg/d); patients
      also received azathioprine (1-2 mg/kg/d).
    explanation: >-
      The older trial supports efficacy only within a noncirrhotic study
      population and predates the current guidance.
  - reference: "url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/"
    reference_title: "New EASL Clinical Practice Guidelines on the management of Autoimmune Hepatitis - EASL-The Home of Hepatology."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Budesonide, which had previously been recommended as part of first-line
      therapy, is no longer endorsed due to concerns regarding its safety and
      overall effectiveness.
    explanation: >-
      The official 2025 guideline summary resolves the current representation.
classifications:
  harrisons_chapter:
  - classification_value: GASTROINTESTINAL
    evidence:
    - reference: PMID:40348684
      reference_title: EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Autoimmune hepatitis (AIH) is a chronic liver disease of unknown
        aetiology which may affect any patient irrespective of age, sex, or
        ethnicity.
      explanation: >-
        The guideline directly identifies AIH as a chronic liver disease,
        supporting the gastrointestinal and hepatology classification.
  - classification_value: IMMUNE_RHEUMATOLOGIC
    evidence:
    - reference: PMID:36746473
      reference_title: Diagnosis and management of autoimmune hepatitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        An abnormal immune response targeting liver autoantigens and inducing
        persistent and self-perpetuating liver inflammation is the pathogenic
        mechanism of the disease.
      explanation: >-
        The review directly identifies an abnormal autoantigen-directed immune
        response, supporting the immune and rheumatologic classification.
notes: >-
  Disease boundary: this entry represents idiopathic autoimmune hepatitis. It
  excludes drug-induced autoimmune-like hepatitis, immune-checkpoint-inhibitor
  hepatitis, and isolated PBC/PSC. AIH-PBC/PSC variant syndromes require combined
  hepatitic and cholangiopathic assessment and are not collapsed into historical
  autoantibody-defined type 1/type 2 labels.
review_notes: >-
  Full re-review completed 2026-07-21. The causal graph was rebuilt around
  ancestry-dependent polygenic susceptibility, autoantigen-specific adaptive
  immunity, hepatocyte injury, interface hepatitis, and fibrogenesis. The prior
  incorrect claim that CD8 T cells kill MHC-class-II-expressing hepatocytes and
  the weakly supported standalone regulatory-T-cell-deficiency node were
  removed. Autoantibodies are modeled as diagnostic immune outputs rather than
  assumed direct effectors. Existing updated_date was preserved per review
  workflow. ClinicalTrials.gov v2 audit paginated through 110 primary-condition
  records (100 plus 10) and cross-checked exact-condition, exact-phrase
  full-text, and AIH-acronym searches on 2026-07-21; eight active or planned
  direct-AIH studies with explicit boundary/staleness notes are represented.
  Mixed post-transplant studies without an AIH-specific cohort and broad
  refractory-autoimmunity baskets were excluded. GSE216064 is the only retained
  AIH-focused public molecular dataset; mixed-liver datasets in which AIH is an
  inseparable control subset were not promoted.
references:
- reference: PMID:40348684
  title: EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
- reference: "url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/"
  title: New EASL Clinical Practice Guidelines on the management of Autoimmune Hepatitis - EASL-The Home of Hepatology.
- reference: PMID:31863477
  title: "Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases."
- reference: PMID:36746473
  title: Diagnosis and management of autoimmune hepatitis.
- reference: PMID:29644994
  title: Autoimmune hepatitis.
- reference: PMID:39817450
  title: Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
- reference: PMID:24768677
  title: Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
- reference: PMID:38089552
  title: Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1.
- reference: PMID:37876996
  title: "Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis."
- reference: PMID:18537184
  title: Simplified criteria for the diagnosis of autoimmune hepatitis.
- reference: PMID:38101756
  title: An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis.
- reference: PMID:20600032
  title: Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis.
- reference: PMID:38340154
  title: "Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis."
- reference: PMID:20862497
  title: "Discrimination of autoimmune hepatitis: autoantibody typing and beyond."
- reference: PMID:25574080
  title: "Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics."
- reference: PMID:24240053
  title: Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis.
- reference: "url:https://www.niddk.nih.gov/health-information/liver-disease/autoimmune-hepatitis/symptoms-causes"
  title: Symptoms & Causes of Autoimmune Hepatitis - NIDDK
- reference: DOI:10.3389/fphar.2022.1077468
  title: "Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives"
📚

References & Deep Research

References

18
PMID:40348684
EASL Clinical Practice Guidelines on the management of autoimmune hepatitis.
No top-level findings curated for this source.
url:https://easl.eu/news/easl-cpgs-autoimmune-hepatitis-2025/
New EASL Clinical Practice Guidelines on the management of Autoimmune Hepatitis - EASL-The Home of Hepatology.
No top-level findings curated for this source.
PMID:31863477
Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases.
No top-level findings curated for this source.
PMID:36746473
Diagnosis and management of autoimmune hepatitis.
No top-level findings curated for this source.
PMID:29644994
Autoimmune hepatitis.
No top-level findings curated for this source.
PMID:39817450
Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.
No top-level findings curated for this source.
PMID:24768677
Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
No top-level findings curated for this source.
PMID:38089552
Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1.
No top-level findings curated for this source.
PMID:37876996
Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis.
No top-level findings curated for this source.
PMID:18537184
Simplified criteria for the diagnosis of autoimmune hepatitis.
No top-level findings curated for this source.
PMID:38101756
An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis.
No top-level findings curated for this source.
PMID:20600032
Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis.
No top-level findings curated for this source.
PMID:38340154
Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis.
No top-level findings curated for this source.
PMID:20862497
Discrimination of autoimmune hepatitis: autoantibody typing and beyond.
No top-level findings curated for this source.
PMID:25574080
Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics.
No top-level findings curated for this source.
PMID:24240053
Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis.
No top-level findings curated for this source.
No top-level findings curated for this source.
DOI:10.3389/fphar.2022.1077468
Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives
No top-level findings curated for this source.

Deep Research

2
Disorder ▸

Disorder

  • Name: Autoimmune Hepatitis
  • Category: Autoimmune
  • Existing deep-research providers: falcon
  • Existing evidence reference count in YAML: 16

Key Pathophysiology Nodes

  • T Cell-Mediated Hepatocyte Destruction
  • Autoantibody Production
  • Regulatory T Cell Deficiency
  • Deep research literature mapping

Citation Inventory (for evidence mapping)

  • DOI:10.1007/s12072-024-10695-1
  • DOI:10.1016/j.jhepr.2023.100926
  • DOI:10.1055/s-0039-1688751
  • DOI:10.1172/jci183776
  • DOI:10.1186/s12967-024-05173-z
  • DOI:10.1371/journal.pone.0335605
  • DOI:10.3389/fcimb.2024.1337223
  • DOI:10.3389/fimmu.2022.984083
  • DOI:10.3389/fimmu.2023.1326078
  • DOI:10.3389/fphar.2022.1077468
Falcon ▸
Disease Pathophysiology Research Report
Edison Scientific Literature 31 citations 2025-12-18T09:56:25.370475

Disease Pathophysiology Research Report

Target Disease - Disease Name: Autoimmune Hepatitis (AIH) - MONDO ID: not retrieved in this search - Category: Autoimmune

Pathophysiology overview Autoimmune hepatitis is a chronic, immune-mediated inflammatory liver disease characterized by serum IgG elevation, autoantibodies, and interface hepatitis with a lymphoplasmacytic infiltrate. Genetic predisposition is dominated by HLA risk alleles; adaptive immunity against liver autoantigens (notably SepSecS/SLA, CYP2D6, FTCD/LC1) is driven by autoreactive CD4+ T cells and B cells with class-switched, affinity-matured responses. Disruption of tolerance involves T cell activation/exhaustion programs and B cell antigen presentation. Hepatic injury and fibrosis are propagaged by inflammatory cytokine signaling pathways and sustained immune cell infiltration. Gut–liver axis perturbations (metabolites and barrier dysfunction) further amplify hepatic immune activation. Immune checkpoint modulation can precipitate a clinically similar immune-mediated hepatitis, underscoring a T cell–centric mechanism of injury. (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3, sun2024thesignificanceof pages 1-2, liu2023immunemediatedhepatitisinduced pages 1-2, kocheise2024pd1pdl1immunecheckpoint pages 1-2)

1) Core pathophysiology: key mechanisms, pathways, processes - Genetic susceptibility (HLA): Fine-mapping in 1,622 AIH type 1 cases (Han Chinese) identified independent MHC signals with strongest association at HLA-B35:01 (OR 7.32), additional HLA-B08:01 and rs7765379, and peptide-binding groove residue HLA-B Phe67, with transethnic support for classic DRB1 alleles (DRB103:01, DRB104:01/04:05) known in European cohorts. Quote: “A total of 588 HLA variants were significantly associated with AIH… the strongest allele was in the HLA-B gene (HLA-B35:01, p = 8.17×10−304; OR = 7.32)… position 67… phenylalanine of the HLA-B molecule… at the peptide binding groove.” (JHEP Reports, 2024-01 online, https://doi.org/10.1016/j.jhepr.2023.100926) (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - Non-HLA risk: Case-control genetics in North Indian adults reported predisposition with HLA-DRB103 and implicated non-HLA immune-regulatory loci CTLA4 and PTPN22 polymorphisms in AIH susceptibility. (Frontiers in Immunology, 2023-01, https://doi.org/10.3389/fimmu.2022.984083) (ahuja2023hlaandnonhla pages 10-11) - Autoantigens and adaptive autoimmunity: Clonal B/T-cell analysis demonstrates anti-SepSecS (SLA) responses are class-switched (IgG1), affinity-matured, recognizing multiple epitopes, with SepSecS-specific CD4+ T cell clones producing IFN-γ, IL-4 and IL-10 and clonal expansion detectable in blood and liver. Quote: “The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured… SepSecS-specific CD4+ T cell clones… produced IFN-γ, IL-4, and IL-10… clonally expanded in both blood and liver biopsy.” (J Clin Invest, 2025-01, https://doi.org/10.1172/JCI183776) (kramer2025clonalanalysisof pages 1-2) - B cells and plasma cells: B cells contribute via antigen presentation to autoreactive T cells, autoantibody production, cytokine generation (promoting Th1/Th17), and inhibition of Treg/Breg; B cell–targeted therapy is effective in refractory AIH, supporting mechanistic involvement. (Semin Liver Dis, 2019-11, https://doi.org/10.1055/s-0039-1688751) (taylor2019thecontributionof pages 1-3) - T cell dysregulation and checkpoints: In immune checkpoint inhibitor (ICI)–mediated hepatitis, the mechanism is “mainly the overactivation of T cells,” providing a human model of T cell–driven hepatic autoimmunity that resembles AIH. Quote: “the mechanism of IMH induced by immune checkpoint inhibitors is mainly the overactivation of T cells.” (Frontiers in Pharmacology, 2023-01, https://doi.org/10.3389/fphar.2022.1077468) (liu2023immunemediatedhepatitisinduced pages 1-2) - Microbiome–gut–liver axis: AIH is associated with reduced bacterial diversity and altered metabolites—decreased secondary bile acids, SCFAs, polyamines; increased LPS and certain amino acid metabolites—implicated in immune activation via PRR and cytokine pathways. Quote: “decreased in secondary bile acids, short-chain fatty acids (SCFAs), and polyamines, and increased in lipopolysaccharide (LPS)… can disrupt immune homeostasis by activating various immune cells and immune-related signaling pathways.” (Frontiers in Cellular and Infection Microbiology, 2024-02, https://doi.org/10.3389/fcimb.2024.1337223) (sun2024thesignificanceof pages 1-2) - Fibrosis signaling: While specific single-cell fibrosis programs were not directly profiled in AIH in the retrieved texts, inflammatory cytokines (e.g., IFN-γ, IL-17 family), chemokines (e.g., CXCL10 cited in related AIH transcriptomics), and canonical pathways (NF-κB, JAK–STAT) are implicated by proximity to T cell/B cell activation, and by overlap with immune-mediated hepatitis biology. (chi2025decodingthedistinct pages 16-16, liu2023immunemediatedhepatitisinduced pages 1-2)

2) Key molecular players - Genes/Proteins (HGNC): - HLA-DRB1 (risk alleles DRB103:01, DRB104 subtypes), HLA-B (notably B35:01; peptide-binding residue 67), HLA-DQB1 (e.g., DQB104:01, *06:02) (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - CTLA4 (Cytotoxic T-lymphocyte–associated protein 4) (ahuja2023hlaandnonhla pages 10-11) - PTPN22 (Protein tyrosine phosphatase non-receptor type 22) (ahuja2023hlaandnonhla pages 10-11) - SEPSECS (SLA/LP antigen), CYP2D6 (LKM1 antigen), FTCD (LC1 antigen) (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Cytokines: IFNG, IL4, IL10 (produced by SepSecS-specific CD4+ T cells) (kramer2025clonalanalysisof pages 1-2) - Chemical entities (ChEBI): - Short-chain fatty acids (e.g., butyrate), secondary bile acids, lipopolysaccharide (LPS) (sun2024thesignificanceof pages 1-2) - Cell types (CL): - CD4+ T cells (CL:0000624); Regulatory T cells (Tregs, CL:0000815); Th17 cells (CL:0000894); Peripheral helper/Tfh-like CD4+ cells (inferred from B cell help); CD8+ T cells (CL:0000625); B cells (CL:0000236); Plasma cells (CL:0000786) (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Anatomical locations (UBERON): - Liver (UBERON:0002107), portal tracts/interface; bile ducts (UBERON:0002394) (context of overlap syndromes) (taylor2019thecontributionof pages 1-3)

3) Biological processes (GO terms) implicated - Antigen processing and presentation of peptide antigen via MHC class I/II (GO:0042590; GO:0019882) – supported by HLA fine mapping and peptide-binding residue association (HLA-B 67) (li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - T cell activation and differentiation, including regulation of T cell activation (GO:0050863), Th1/Th2/Th17 differentiation (GO:0042093; GO:0042094; GO:1902105) – reflected by SepSecS-specific CD4+ T cell cytokine profiles and B cell cytokine effects (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - B cell activation, antigen presentation and immunoglobulin production (GO:0042113; GO:0002376; GO:0002377) – based on B cell roles and affinity-matured anti-SepSecS antibodies (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Response to lipopolysaccharide (GO:0032496), bile acid metabolic process (GO:0008206), and SCFA signaling (GO processes related to GPCR signaling) – microbiome-mediated immune activation (sun2024thesignificanceof pages 1-2) - Cytokine-mediated signaling pathways including JAK–STAT (GO:0007259) and NF-κB (GO:0043122) – inferred from immune activation and IMH pathophysiology (liu2023immunemediatedhepatitisinduced pages 1-2)

4) Cellular components - MHC class I/II protein complexes (GO:0042612; GO:0042611) (li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - Immunological synapse (GO:0001772) – site of T–B interaction and T cell activation (taylor2019thecontributionof pages 1-3) - Plasma membrane (GO:0005886) – CTLA4, TCR signaling; endoplasmic reticulum/Golgi – immunoglobulin synthesis and glycosylation (supported by plasma glycome signatures) (pongracz2024autoimmunehepatitisdisplays pages 1-2) - Extracellular space (GO:0005615) – circulating IgG, polyreactive IgG, cytokines (engel2024detectionofpolyreactive pages 1-2)

5) Disease progression: sequence of events - Initiation: Genetic susceptibility (HLA class II and class I loci; non-HLA CTLA4/PTPN22) permits presentation of liver/self antigens. Environmental triggers (infections, dysbiosis) alter antigenic load and innate signaling (e.g., LPS) along the gut–liver axis, lowering tolerance thresholds. (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5, ahuja2023hlaandnonhla pages 10-11, sun2024thesignificanceof pages 1-2) - Autoimmunity establishment: Autoreactive CD4+ T cells recognizing SepSecS (SLA) and other autoantigens expand, providing B-cell help; B cells undergo affinity maturation and produce class-switched antibodies. (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Hepatocellular injury: Cytokine-driven inflammation and cytotoxic T cell activity produce interface hepatitis; persistent activation engages pro-fibrotic remodeling pathways (inflammatory chemokines/cytokines; NF-κB/JAK–STAT). (chi2025decodingthedistinct pages 16-16, liu2023immunemediatedhepatitisinduced pages 1-2) - Biomarker manifestations: Hypergammaglobulinemia with elevated IgG; disease-specific biomarker candidates include plasma N-glycome changes (high tetra-antennary sialylation) and polyreactive IgG signatures. (pongracz2024autoimmunehepatitisdisplays pages 1-2, engel2024detectionofpolyreactive pages 1-2)

6) Phenotypic manifestations and links to mechanisms - Elevated transaminases (ALT/AST) and IgG: reflect ongoing T and B cell–mediated hepatic inflammation and plasmacytosis. (taylor2019thecontributionof pages 1-3) - Autoantibody positivity: ANA/SMA for AIH-1; anti-LKM1 and anti-LC1 for AIH-2; anti-SLA/LP (SepSecS) across types, correlating with more severe phenotype; mechanistically linked to affinity-matured anti-SepSecS response. (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Interface hepatitis with plasma cell–rich portal infiltrates: pathologic correlate of B cell and T cell activation. (taylor2019thecontributionof pages 1-3) - Overlap features with PBC/PSC (variant syndromes): shared autoimmunity to biliary structures and HLA backgrounds; clinically recognized overlaps require biopsy/serology correlation. (kocheise2024pd1pdl1immunecheckpoint pages 1-2, taylor2019thecontributionof pages 1-3)

Recent developments (priority 2023–2024) with data, URLs, dates - HLA fine mapping in AIH type 1 (Han Chinese): Identification of HLA-B35:01 (OR 7.32), HLA-B08:01, peptide-binding residue Phe67, and transethnic confirmation of DRB1 risk architecture; association with clinical phenotypes (e.g., higher AST/ALT, lower IgG in B*35:01 carriers). JHEP Reports (online 2024-01-05), https://doi.org/10.1016/j.jhepr.2023.100926 (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - SepSecS (SLA)–specific immunity at clonal resolution in AIH: IgG1, affinity-matured antibodies to multiple epitopes; SepSecS-specific CD4+ T cells producing IFN-γ/IL-4/IL-10; clonal expansion in liver; B cells present SepSecS to T cells. J Clin Invest (2025-01-16 online early), https://doi.org/10.1172/JCI183776 (kramer2025clonalanalysisof pages 1-2) - AIH plasma glycome biomarker: “Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans compared to other liver diseases,” with tetraantennary sialylation per galactose (A4GS) differentiating AIH from other liver diseases. Journal of Translational Medicine (2024-05), https://doi.org/10.1186/s12967-024-05173-z (pongracz2024autoimmunehepatitisdisplays pages 1-2) - Polyreactive IgG (pIgG) improves AIH diagnosis in children (multi-center European cohort, n=285): AUC 0.900 vs non-AIH liver diseases; higher specificity than ANA/ASMA; sensitivity far exceeding anti-SLA/LC1/LKM in pediatric cohorts; independent of treatment response. Hepatology International (2024-07-08), https://doi.org/10.1007/s12072-024-10695-1 (engel2024detectionofpolyreactive pages 1-2) - Microbiome narrative review in AIH: Summarizes decreased SCFAs/secondary bile acids and increased LPS and amino acid metabolites, linking to immune activation and barrier dysfunction along the gut–liver axis. Frontiers in Cellular and Infection Microbiology (2024-02-09), https://doi.org/10.3389/fcimb.2024.1337223 (sun2024thesignificanceof pages 1-2) - ICI-induced immune-mediated hepatitis overview: “Overactivation of T cells” as central mechanism; incidence 1–15%, diagnostic/management considerations; provides mechanistic parallel to T cell–mediated hepatic autoimmunity. Frontiers in Pharmacology (2023-01-09), https://doi.org/10.3389/fphar.2022.1077468 (liu2023immunemediatedhepatitisinduced pages 1-2) - PD-1/PD-L1 inhibitor safety in AILD: Multicenter European series (n=22; 4 AIH) reported no grade ≥3 irAEs and no significant liver test changes over 1 year, suggesting PD-1/PD-L1 agents “appear to be safe” in selected AILD patients with cancer. Frontiers in Immunology (2024-01-10), https://doi.org/10.3389/fimmu.2023.1326078 (kocheise2024pd1pdl1immunecheckpoint pages 1-2)

Current applications and real-world implementations - Diagnostics - Serology: Standard ANA/SMA (AIH-1), LKM1/LC1 (AIH-2), SLA/LP (SepSecS) where available; pIgG quantification may increase diagnostic accuracy in pediatrics and possibly adults. (engel2024detectionofpolyreactive pages 1-2, kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Biomarkers under evaluation: Plasma glycome (A4GS), as a noninvasive discriminator versus other liver diseases; could reduce need for biopsy if validated longitudinally. (pongracz2024autoimmunehepatitisdisplays pages 1-2) - Risk stratification and genetics: HLA typing is informative in research and some clinical contexts (e.g., DRB103/04 risk backgrounds; B*35:01 in East Asian cohorts); associations with phenotype at presentation (enzymes, IgG) reported. (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - Therapeutics - Standard: Corticosteroids ± azathioprine remain first-line (contextualized by B/T cell pathobiology). (taylor2019thecontributionof pages 1-3) - Refractory options: B cell–targeted therapy (e.g., anti-CD20) has shown efficacy in difficult AIH, aligning with B cell role in pathogenesis. (taylor2019thecontributionof pages 1-3) - Safety of PD-1/PD-L1 cancer therapy in AILD: cautious use appears feasible in selected cases with close monitoring. (kocheise2024pd1pdl1immunecheckpoint pages 1-2)

Expert opinions and analyses - B cell centrality and therapeutic targeting: “Autoreactive B cells can promote autoimmunity through antigen presentation to autoreactive T cells, production of autoantibodies… and inhibition of regulatory T cells,” with clinical evidence for B cell–depleting therapy efficacy in refractory AIH. (Semin Liver Dis, 2019, https://doi.org/10.1055/s-0039-1688751) (taylor2019thecontributionof pages 1-3) - T cell–centric injury model from ICI hepatitis: mechanistic insight that loss of checkpoint restraint leads to T cell overactivation and hepatitis provides a human perturbation model analogous to AIH immune injury. (Frontiers in Pharmacology, 2023, https://doi.org/10.3389/fphar.2022.1077468) (liu2023immunemediatedhepatitisinduced pages 1-2)

Relevant statistics and data - HLA associations (Han Chinese AIH type 1): HLA-B35:01 OR 7.32; HLA-B08:01 OR 4.26; lead SNP rs2243621 OR 3.76; peptide-binding residue association HLA-B Phe67 (p=3.39×10−139). (JHEP Reports 2024, https://doi.org/10.1016/j.jhepr.2023.100926) (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - Pediatric pIgG diagnostic performance: AUC 0.900 vs non-AIH liver diseases; 31–73% higher specificity vs ANA/SMA and 6–20× higher sensitivity vs anti-SLA/LC1/LKM in children; positive in 43–75% with normal total IgG. (Hepatology International 2024, https://doi.org/10.1007/s12072-024-10695-1) (engel2024detectionofpolyreactive pages 1-2) - Plasma glycome: Tetraantennary sialylation (A4GS) significantly differentiates AIH from other liver diseases; bisection tracks cirrhosis severity. (Journal of Translational Medicine 2024, https://doi.org/10.1186/s12967-024-05173-z) (pongracz2024autoimmunehepatitisdisplays pages 1-2) - ICI hepatitis epidemiology: IMH incidence 1–15% across settings; pathogenesis attributed to T cell overactivation. (Frontiers in Pharmacology 2023, https://doi.org/10.3389/fphar.2022.1077468) (liu2023immunemediatedhepatitisinduced pages 1-2) - PD-1/PD-L1 safety in AILD with cancer: 22 patients (12 PBC, 5 PSC, 4 AIH, 1 AIH-PSC) – no grade ≥3 irAEs; no significant liver test changes in first year. (Frontiers in Immunology 2024, https://doi.org/10.3389/fimmu.2023.1326078) (kocheise2024pd1pdl1immunecheckpoint pages 1-2)

Structured knowledge base annotations - Genes/Proteins (HGNC): HLA-DRB1; HLA-B; HLA-DQB1; CTLA4; PTPN22; SEPSECS (SLA/LP antigen); CYP2D6 (LKM1 antigen); FTCD (LC1 antigen). Evidence: HLA fine mapping; case-control genetics; clonal SepSecS immunity; established autoantibody specificities. (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5, ahuja2023hlaandnonhla pages 10-11, kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - GO Biological Process: Antigen presentation via MHC I/II; T cell activation and differentiation (Th1/Th2/Th17); B cell activation and immunoglobulin production; response to LPS; bile acid metabolism; cytokine-mediated signaling (JAK–STAT; NF-κB). (li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5, kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3, sun2024thesignificanceof pages 1-2, liu2023immunemediatedhepatitisinduced pages 1-2) - Cellular Components: MHC complexes; immunological synapse; plasma membrane; ER/Golgi (IgG glycosylation); extracellular region (serum IgG/pIgG). (pongracz2024autoimmunehepatitisdisplays pages 1-2, engel2024detectionofpolyreactive pages 1-2) - Cell types (CL): CD4+ T cell; Treg; Th17 cell; CD8+ T cell; B cell; Plasma cell. (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Anatomical locations (UBERON): Liver; portal tracts; bile ducts. (taylor2019thecontributionof pages 1-3) - Phenotypes (HPO): Hypergammaglobulinemia; Elevated serum IgG; Autoantibody positivity; Interface hepatitis; Overlap cholangiopathy features. (taylor2019thecontributionof pages 1-3, engel2024detectionofpolyreactive pages 1-2, pongracz2024autoimmunehepatitisdisplays pages 1-2) - Chemical entities (ChEBI): SCFAs (e.g., butyrate); secondary bile acids; LPS. (sun2024thesignificanceof pages 1-2)

Direct evidence quotes (illustrative) - “A total of 588 HLA variants were significantly associated with AIH… the strongest allele was in the HLA-B gene (HLA-B*35:01, p = 8.17×10−304; OR = 7.32)… position 67… phenylalanine of the HLA-B molecule… at the peptide binding groove.” (JHEP Reports 2024) (li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - “The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured… SepSecS-specific CD4+ T cell clones… produced IFN-γ, IL-4, and IL-10, … clonally expanded in both blood and liver biopsy.” (J Clin Invest 2025) (kramer2025clonalanalysisof pages 1-2) - “the mechanism of IMH induced by immune checkpoint inhibitors is mainly the overactivation of T cells.” (Frontiers in Pharmacology 2023) (liu2023immunemediatedhepatitisinduced pages 1-2) - “decreased in secondary bile acids, short-chain fatty acids (SCFAs), and polyamines, and increased in lipopolysaccharide (LPS)… can disrupt immune homeostasis…” (Frontiers in Cellular and Infection Microbiology 2024) (sun2024thesignificanceof pages 1-2) - “Glycan traits… tetraantennary sialylation per galactose (A4GS)… were found as discriminators between AIH and healthy controls… High A4GS differentiated AIH from other liver diseases.” (Journal of Translational Medicine 2024) (pongracz2024autoimmunehepatitisdisplays pages 1-2) - “pIgG had an AUC of 0.900… 31–73% higher specificity than ANA and anti-SMA… 6–20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM.” (Hepatology International 2024) (engel2024detectionofpolyreactive pages 1-2)

Open questions and limits of current evidence - The relative contributions of specific T helper lineages (e.g., Th17/Treg balance) and innate-like T cells (e.g., MAIT/NKT) in human AIH liver tissue require more single-cell/functional datasets; current mechanistic anchors are supported by clonal anti-SepSecS responses and B cell roles, rather than comprehensive spatial-omics in AIH. (kramer2025clonalanalysisof pages 1-2, taylor2019thecontributionof pages 1-3) - Microbiome causality versus consequence remains unresolved; however, convergent metabolite patterns (SCFAs↓, secondary bile acids↓, LPS↑) provide plausible immunologic levers. (sun2024thesignificanceof pages 1-2)

References (with URLs and dates) - Li Y et al. Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1. JHEP Reports. Online 2024-01-05. https://doi.org/10.1016/j.jhepr.2023.100926 (li2024finemappingidentifies pages 1-2, li2024finemappingidentifies pages 2-4, li2024finemappingidentifies pages 4-5) - Kramer M et al. Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis. J Clin Invest. 2025-01-16. https://doi.org/10.1172/JCI183776 (kramer2025clonalanalysisof pages 1-2) - Taylor SA, Assis DN, Mack CL. The Contribution of B Cells in Autoimmune Liver Diseases. Semin Liver Dis. 2019-11. https://doi.org/10.1055/s-0039-1688751 (taylor2019thecontributionof pages 1-3) - Engel B et al. Detection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis. Hepatology International. 2024-07-08. https://doi.org/10.1007/s12072-024-10695-1 (engel2024detectionofpolyreactive pages 1-2) - Pongracz T et al. Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans… J Transl Med. 2024-05. https://doi.org/10.1186/s12967-024-05173-z (pongracz2024autoimmunehepatitisdisplays pages 1-2) - Sun C et al. The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review. Front Cell Infect Microbiol. 2024-02-09. https://doi.org/10.3389/fcimb.2024.1337223 (sun2024thesignificanceof pages 1-2) - Liu Z et al. Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives. Front Pharmacol. 2023-01-09. https://doi.org/10.3389/fphar.2022.1077468 (liu2023immunemediatedhepatitisinduced pages 1-2) - Kocheise L et al. PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety… AILD. Front Immunol. 2024-01-10. https://doi.org/10.3389/fimmu.2023.1326078 (kocheise2024pd1pdl1immunecheckpoint pages 1-2) - Ahuja N et al. HLA and Non-HLA gene polymorphisms in autoimmune hepatitis patients of North Indian adults. Front Immunol. 2023-01. https://doi.org/10.3389/fimmu.2022.984083 (ahuja2023hlaandnonhla pages 10-11) - Chi G et al. Integrated scRNA-seq/bulk RNA-seq landscape in AIH (supportive evidence for cytotoxic and chemokine axes). PLOS One. 2025-12. https://doi.org/10.1371/journal.pone.0335605 (chi2025decodingthedistinct pages 16-16)

References

  1. (kramer2025clonalanalysisof pages 1-2): Michael Kramer, F. Mele, Sandra Jovic, Blanca Fernandez, D. Jarrossay, Jun Siong Low, Christiane Sokollik, Magdalena Filipowicz Sinnreich, Sylvie Ferrari-Lacraz, G. Mieli-Vergani, D. Vergani, Antonio Lanzavecchia, Antonino Cassotta, B. Terziroli Beretta‐Piccoli, and Federica Sallusto. Clonal analysis of sepsecs-specific b and t cells in autoimmune hepatitis. The Journal of Clinical Investigation, Jan 2025. URL: https://doi.org/10.1172/jci183776, doi:10.1172/jci183776. This article has 11 citations.

  2. (taylor2019thecontributionof pages 1-3): Sarah A. Taylor, David N. Assis, and Cara L. Mack. The contribution of b cells in autoimmune liver diseases. Seminars in Liver Disease, 39:422-431, Jun 2019. URL: https://doi.org/10.1055/s-0039-1688751, doi:10.1055/s-0039-1688751. This article has 78 citations and is from a peer-reviewed journal.

  3. (sun2024thesignificanceof pages 1-2): Chen Sun, Dongzi Zhu, Qi Zhu, Zeping He, Yichao Lou, and Desheng Chen. The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review. Frontiers in Cellular and Infection Microbiology, Feb 2024. URL: https://doi.org/10.3389/fcimb.2024.1337223, doi:10.3389/fcimb.2024.1337223. This article has 17 citations and is from a poor quality or predatory journal.

  4. (liu2023immunemediatedhepatitisinduced pages 1-2): Zherui Liu, Yun Zhu, Huan Xie, and Zhengsheng Zou. Immune-mediated hepatitis induced by immune checkpoint inhibitors: current updates and future perspectives. Frontiers in Pharmacology, Jan 2023. URL: https://doi.org/10.3389/fphar.2022.1077468, doi:10.3389/fphar.2022.1077468. This article has 59 citations and is from a poor quality or predatory journal.

  5. (kocheise2024pd1pdl1immunecheckpoint pages 1-2): Lorenz Kocheise, Ignazio Piseddu, Joscha Vonderlin, Eric T. Tjwa, Gustav Buescher, Lucy Meunier, Pia Goeggelmann, Francesca Fianchi, Jérôme Dumortier, Mar Riveiro Barciela, Tom J. G. Gevers, Benedetta Terziroli Beretta-Piccoli, Maria-Carlota Londoño, Sona Frankova, Thomas Roesner, Vincent Joerg, Constantin Schmidt, Fabian Glaser, Jan P. Sutter, Thorben W. Fründt, Ansgar W. Lohse, Samuel Huber, Johann von Felden, Marcial Sebode, and Kornelius Schulze. Pd-1/pd-l1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease. Frontiers in Immunology, Jan 2024. URL: https://doi.org/10.3389/fimmu.2023.1326078, doi:10.3389/fimmu.2023.1326078. This article has 16 citations and is from a peer-reviewed journal.

  6. (li2024finemappingidentifies pages 1-2): You Li, Lu Zhou, Zuxiong Huang, Yue Yang, Jiming Zhang, Ling Yang, Yun Xu, Junping Shi, Shanhong Tang, Xiaoling Yuan, Jie Xu, Yiling Li, Xu Han, Jia Li, Yanmin Liu, Ying Sun, Xiaozhi Jin, Xiao Xiao, Bangmao Wang, Qiuxiang Lin, Yang Zhou, Xuejiao Song, Yong Cui, Lilin Hu, Yuhu Song, Jie Bao, Ling Gong, M. Eric Gershwin, Xianbo Zuo, Huiping Yan, Zhengsheng Zou, Ruqi Tang, and Xiong Ma. Fine mapping identifies independent hla associations in autoimmune hepatitis type 1. JHEP Reports, 6:100926, Jan 2024. URL: https://doi.org/10.1016/j.jhepr.2023.100926, doi:10.1016/j.jhepr.2023.100926. This article has 6 citations and is from a peer-reviewed journal.

  7. (li2024finemappingidentifies pages 2-4): You Li, Lu Zhou, Zuxiong Huang, Yue Yang, Jiming Zhang, Ling Yang, Yun Xu, Junping Shi, Shanhong Tang, Xiaoling Yuan, Jie Xu, Yiling Li, Xu Han, Jia Li, Yanmin Liu, Ying Sun, Xiaozhi Jin, Xiao Xiao, Bangmao Wang, Qiuxiang Lin, Yang Zhou, Xuejiao Song, Yong Cui, Lilin Hu, Yuhu Song, Jie Bao, Ling Gong, M. Eric Gershwin, Xianbo Zuo, Huiping Yan, Zhengsheng Zou, Ruqi Tang, and Xiong Ma. Fine mapping identifies independent hla associations in autoimmune hepatitis type 1. JHEP Reports, 6:100926, Jan 2024. URL: https://doi.org/10.1016/j.jhepr.2023.100926, doi:10.1016/j.jhepr.2023.100926. This article has 6 citations and is from a peer-reviewed journal.

  8. (li2024finemappingidentifies pages 4-5): You Li, Lu Zhou, Zuxiong Huang, Yue Yang, Jiming Zhang, Ling Yang, Yun Xu, Junping Shi, Shanhong Tang, Xiaoling Yuan, Jie Xu, Yiling Li, Xu Han, Jia Li, Yanmin Liu, Ying Sun, Xiaozhi Jin, Xiao Xiao, Bangmao Wang, Qiuxiang Lin, Yang Zhou, Xuejiao Song, Yong Cui, Lilin Hu, Yuhu Song, Jie Bao, Ling Gong, M. Eric Gershwin, Xianbo Zuo, Huiping Yan, Zhengsheng Zou, Ruqi Tang, and Xiong Ma. Fine mapping identifies independent hla associations in autoimmune hepatitis type 1. JHEP Reports, 6:100926, Jan 2024. URL: https://doi.org/10.1016/j.jhepr.2023.100926, doi:10.1016/j.jhepr.2023.100926. This article has 6 citations and is from a peer-reviewed journal.

  9. (ahuja2023hlaandnonhla pages 10-11): Nishtha Ahuja, Jagdeep Singh, Ranjana Walker Minz, Shashi Anand, Ashim Das, and Sunil Taneja. Hla and non-hla gene polymorphisms in autoimmune hepatitis patients of north indian adults. Frontiers in Immunology, Jan 2023. URL: https://doi.org/10.3389/fimmu.2022.984083, doi:10.3389/fimmu.2022.984083. This article has 8 citations and is from a peer-reviewed journal.

  10. (chi2025decodingthedistinct pages 16-16): Gang Chi, Yijia Che, Jinhong Pei, Xueqing Li, and Junmei Wang. Decoding the distinct immune landscape and possible regulatory mechanisms of autoimmune hepatitis through integrated single-cell and bulk rna sequencing. PLOS One, 20:e0335605, Dec 2025. URL: https://doi.org/10.1371/journal.pone.0335605, doi:10.1371/journal.pone.0335605. This article has 0 citations and is from a peer-reviewed journal.

  11. (pongracz2024autoimmunehepatitisdisplays pages 1-2): Tamas Pongracz, Maaike Biewenga, Anna Eva Charlotte Stoelinga, Marco René Bladergroen, Simone Nicolardi, Leendert Adrianus Trouw, Manfred Wuhrer, Noortje de Haan, and Bart van Hoek. Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma n-glycans compared to other liver diseases. Journal of Translational Medicine, May 2024. URL: https://doi.org/10.1186/s12967-024-05173-z, doi:10.1186/s12967-024-05173-z. This article has 8 citations and is from a peer-reviewed journal.

  12. (engel2024detectionofpolyreactive pages 1-2): Bastian Engel, Jana Diestelhorst, Katharina Luise Hupa-Breier, Theresa Kirchner, Nicole Henjes, Stephanie Loges, Muhammed Yuksel, Wojciech Janczyk, Claudine Lalanne, Kalliopi Zachou, Ye H. Oo, Jérôme Gournay, Simon Pape, Joost P. H. Drenth, Amédée Renand, George N. Dalekos, Luigi Muratori, Piotr Socha, Yun Ma, Cigdem Arikan, Ulrich Baumann, Michael P. Manns, Heiner Wedemeyer, Norman Junge, Elmar Jaeckel, and Richard Taubert. Detection of polyreactive immunoglobulin g facilitates diagnosis in children with autoimmune hepatitis. Hepatology International, 18:1214-1226, Jul 2024. URL: https://doi.org/10.1007/s12072-024-10695-1, doi:10.1007/s12072-024-10695-1. This article has 9 citations and is from a peer-reviewed journal.