Sclerosing cholangitis is a fibroinflammatory cholangiopathy in which inflammation and fibrosis progressively narrow and damage intrahepatic and/or extrahepatic bile ducts, causing cholestasis, cholestatic symptoms, and risk of downstream liver injury. The root concept includes primary, secondary, IgG4-related, and neonatal forms whose upstream triggers differ but converge on bile-duct stenosis and destruction.
Ask a research question about Sclerosing Cholangitis. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Sclerosing Cholangitis
creation_date: "2026-05-07T15:54:15Z"
updated_date: "2026-05-07T17:04:52Z"
category: Complex
parents:
- Liver Disease
- Cholangiopathy
synonyms:
- Sclerosing cholangitis
disease_term:
preferred_term: sclerosing cholangitis
term:
id: MONDO:0018646
label: sclerosing cholangitis
description: >-
Sclerosing cholangitis is a fibroinflammatory cholangiopathy in which
inflammation and fibrosis progressively narrow and damage intrahepatic and/or
extrahepatic bile ducts, causing cholestasis, cholestatic symptoms, and risk
of downstream liver injury. The root concept includes primary, secondary,
IgG4-related, and neonatal forms whose upstream triggers differ but converge
on bile-duct stenosis and destruction.
has_subtypes:
- name: Primary sclerosing cholangitis
subtype_term:
preferred_term: primary sclerosing cholangitis
term:
id: MONDO:0013433
label: primary sclerosing cholangitis
description: >-
Idiopathic chronic sclerosing cholangitis strongly associated with
inflammatory bowel disease and progressive multifocal bile-duct strictures.
- name: Secondary sclerosing cholangitis
subtype_term:
preferred_term: secondary sclerosing cholangitis
term:
id: MONDO:0018647
label: secondary sclerosing cholangitis
description: >-
Sclerosing cholangitis caused by identifiable secondary injuries such as
ischemic, infectious, toxic, obstructive, or post-critical-illness bile-duct
damage.
- name: IgG4-related sclerosing cholangitis
subtype_term:
preferred_term: IgG4-related sclerosing cholangitis
term:
id: MONDO:0018645
label: IgG4-related sclerosing cholangitis
description: >-
Biliary manifestation of IgG4-related disease, often associated with
autoimmune pancreatitis and steroid responsiveness.
- name: Neonatal ichthyosis-sclerosing cholangitis syndrome
subtype_term:
preferred_term: neonatal ichthyosis-sclerosing cholangitis syndrome
term:
id: MONDO:0011874
label: neonatal ichthyosis-sclerosing cholangitis syndrome
description: >-
Syndromic neonatal form with sclerosing cholangitis and ichthyosis.
- name: Isolated neonatal sclerosing cholangitis
subtype_term:
preferred_term: isolated neonatal sclerosing cholangitis
term:
id: MONDO:0018816
label: isolated neonatal sclerosing cholangitis
description: >-
Neonatal sclerosing cholangitis without the syndromic ichthyosis component.
progression:
- phase: Chronic fibroinflammatory cholangiopathy
notes: >-
Sclerosing cholangitis is usually chronic and progressive, with persistent
biliary inflammation, ductal obliteration, hepatic dysfunction, and eventual
risk of cirrhosis.
evidence:
- reference: DOI:10.3390/jcm15031149
reference_title: Primary Sclerosing Cholangitis in 2026
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Primary sclerosing cholangitis is a rare, chronic, inflammatory disease
of the biliary tree that leads to progressive ductal obliteration,
hepatic dysfunction, and ultimately liver cirrhosis.
explanation: >-
Supports chronic progression from biliary inflammation and ductal
obliteration to hepatic dysfunction and cirrhosis.
- phase: Advanced complications
notes: >-
Advanced disease can require transplantation and PSC-IBD carries elevated
colorectal and cholangiocarcinoma surveillance burden.
evidence:
- reference: DOI:10.3390/cancers17132165
reference_title: Navigating Neoplasm Risk in Inflammatory Bowel Disease and
Primary Sclerosing Cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients with inflammatory bowel disease (IBD) and primary sclerosing
cholangitis (PSC) face a significantly increased risk of malignancies,
including a 10-fold higher risk for colorectal cancer (CRC) and a
lifetime risk for cholangiocarcinoma (CCA) exceeding 20%.
explanation: >-
Supports malignancy risk as a major advanced-disease surveillance issue
in PSC-IBD.
pathophysiology:
- name: Gut-Liver Axis Barrier Disruption and Dysbiosis
description: >-
In primary sclerosing cholangitis, intestinal barrier disruption and
dysbiosis permit microbial products to reach the portal circulation and
amplify hepatobiliary immune activation.
biological_processes:
- preferred_term: inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
downstream:
- target: Hepatic Innate Immune Activation
description: Portal microbial products stimulate hepatic innate immune cells.
evidence:
- reference: DOI:10.3390/jcm14217817
reference_title: 'Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response
in Pathogenesis of Primary Sclerosing Cholangitis: An Overview'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In particular, disruption of the intestinal barrier allows microbial
products to enter the portal circulation, stimulating hepatic immune cells
and triggering biliary inflammation.
explanation: >-
Supports gut-barrier disruption and portal microbial delivery as an
upstream inflammatory mechanism in PSC.
- reference: DOI:10.3390/jcm14217817
reference_title: 'Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response
in Pathogenesis of Primary Sclerosing Cholangitis: An Overview'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Dysbiosis, characterized by reduced microbial diversity and the expansion
of bile-tolerant and pro-inflammatory taxa, amplifies this immune
activation and disturbs gut–liver homeostasis.
explanation: >-
Supports dysbiosis as an amplifier of PSC immune activation.
- name: Hepatic Innate Immune Activation
description: >-
Microbial and cholestatic signals activate cholangiocytes and liver
macrophages, producing inflammatory cytokine and chemokine signaling in the
biliary tree.
cell_types:
- preferred_term: Cholangiocyte
term:
id: CL:1000488
label: cholangiocyte
- preferred_term: Kupffer cell / liver macrophage
term:
id: CL:0000235
label: macrophage
biological_processes:
- preferred_term: inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
downstream:
- target: Bile Duct Inflammation
description: Innate inflammatory activation injures the biliary epithelium.
evidence:
- reference: PMID:39250501
reference_title: Central role for cholangiocyte pathobiology in cholestatic
liver diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The crosstalk between cholangiocytes and cells of the innate (neutrophils
and macrophages) and adaptive (T cells and B cells) immune systems is also
examined in detail.
explanation: >-
Supports cholangiocyte interaction with innate and adaptive immune cells
as a central cholangiopathy mechanism.
- name: Aberrant Gut-Primed Lymphocyte Trafficking
description: >-
Gut-primed lymphocytes aberrantly home to the liver and biliary tree,
sustaining antigen-driven cholangiocyte injury in PSC-associated
gut-liver-axis disease.
cell_types:
- preferred_term: CD4-positive T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
- preferred_term: Th17 cell
term:
id: CL:0000899
label: T-helper 17 cell
- preferred_term: regulatory T cell
term:
id: CL:0000815
label: regulatory T cell
biological_processes:
- preferred_term: leukocyte migration
term:
id: GO:0050900
label: leukocyte migration
modifier: ABNORMAL
downstream:
- target: Bile Duct Inflammation
description: Aberrant immune trafficking sustains bile-duct injury.
evidence:
- reference: DOI:10.3390/jcm14217817
reference_title: 'Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response
in Pathogenesis of Primary Sclerosing Cholangitis: An Overview'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Concurrently, gut-primed lymphocytes expressing mucosal homing receptors
migrate aberrantly to the liver, where they may contribute to biliary
epithelial cell injury.
explanation: >-
Supports aberrant lymphocyte trafficking from the gut to liver as a PSC
injury pathway.
- name: Bile Acid Signaling Dysregulation
description: >-
Dysregulated bile-acid receptor signaling in cholangiocytes and the
gut-liver axis promotes cholestasis, inflammation, and fibrotic remodeling.
cell_types:
- preferred_term: Cholangiocyte
term:
id: CL:1000488
label: cholangiocyte
biological_processes:
- preferred_term: bile acid metabolic process
term:
id: GO:0008206
label: bile acid metabolic process
modifier: ABNORMAL
downstream:
- target: Cholestatic Liver Injury
description: Dysregulated bile-acid signaling contributes to cholestasis.
- target: Bile Duct Fibrostenosis
description: Bile-acid dysregulation can promote inflammation and fibrosis.
evidence:
- reference: DOI:10.3390/jcm14217817
reference_title: 'Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response
in Pathogenesis of Primary Sclerosing Cholangitis: An Overview'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Moreover, bile acids act as signaling molecules, regulating metabolism
and immune responses through receptors such as FXR and TGR5.
Dysregulation of these pathways may promote cholestasis, inflammation,
and fibrosis.
explanation: >-
Supports bile-acid signaling dysregulation as a contributor to
cholestasis, inflammation, and fibrosis.
- reference: DOI:10.3390/cells13191650
reference_title: 'Bile Acids-Based Therapies for Primary Sclerosing Cholangitis:
Current Landscape and Future Developments'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recent studies have revealed that these cells undergo a downregulation of
GPBAR1 (TGR5), a bile acid receptor involved in bicarbonate secretion and
immune regulation.
explanation: >-
Supports cholangiocyte bile-acid receptor dysregulation in PSC.
- name: Bile Duct Inflammation
description: >-
Inflammatory injury of the bile-duct epithelium and duct wall is a shared
upstream feature across sclerosing cholangitis categories.
cell_types:
- preferred_term: Cholangiocyte
term:
id: CL:1000488
label: cholangiocyte
- preferred_term: Kupffer cell / liver macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: CD4-positive T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
- preferred_term: Th17 cell
term:
id: CL:0000899
label: T-helper 17 cell
- preferred_term: regulatory T cell
term:
id: CL:0000815
label: regulatory T cell
biological_processes:
- preferred_term: inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
downstream:
- target: Bile Duct Fibrostenosis
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sclerosing cholangitis (SC) is defined as a condition with progressive
stenosis and destruction of the bile ducts due to diffuse inflammation
and fibrosis and currently includes three categories: primary sclerosing
cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing
cholangitis (IgG4-SC).
explanation: >-
This review defines the root condition by bile-duct inflammation,
fibrosis, stenosis, and destruction and identifies major clinical
categories.
- name: Cholangiocyte Senescence-Associated Fibrogenesis
description: >-
Stressed cholangiocytes can acquire a senescence-associated secretory
phenotype that is proinflammatory and profibrogenic, driving crosstalk with
portal fibroblasts and hepatic stellate cells.
cell_types:
- preferred_term: Cholangiocyte
term:
id: CL:1000488
label: cholangiocyte
- preferred_term: Hepatic stellate cell
term:
id: CL:0000632
label: hepatic stellate cell
biological_processes:
- preferred_term: cellular senescence
term:
id: GO:0090398
label: cellular senescence
modifier: INCREASED
- preferred_term: extracellular matrix organization
term:
id: GO:0030198
label: extracellular matrix organization
modifier: INCREASED
downstream:
- target: Bile Duct Fibrostenosis
description: Senescent cholangiocyte signaling promotes periductal fibrosis.
evidence:
- reference: PMID:39250501
reference_title: Central role for cholangiocyte pathobiology in cholestatic
liver diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The proclivity of these cells to undergo a senescence-associated secretory
phenotype, which is proinflammatory and profibrogenic, and the intrinsic
intracellular activation pathways resulting in the secretion of cytokines
and chemokines are reviewed.
explanation: >-
Supports cholangiocyte SASP as a proinflammatory and profibrogenic
mechanism in cholangiopathies.
- name: Bile Duct Fibrostenosis
description: >-
Fibrotic remodeling of affected bile ducts narrows the duct lumen, producing
strictures and downstream cholestasis.
cell_types:
- preferred_term: Hepatic stellate cell
term:
id: CL:0000632
label: hepatic stellate cell
biological_processes:
- preferred_term: extracellular matrix organization
term:
id: GO:0030198
label: extracellular matrix organization
modifier: INCREASED
downstream:
- target: Cholestatic Liver Injury
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sclerosing cholangitis (SC) is defined as a condition with progressive
stenosis and destruction of the bile ducts due to diffuse inflammation
and fibrosis and currently includes three categories: primary sclerosing
cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing
cholangitis (IgG4-SC).
explanation: >-
The definition directly supports progressive bile-duct stenosis and
fibrosis as central shared pathobiology.
- name: Cholestatic Liver Injury
description: >-
Persistent obstruction and cholestasis from bile-duct strictures drive
cholestatic liver injury and can progress to biliary cirrhosis.
biological_processes:
- preferred_term: cholangiocyte apoptotic process
term:
id: GO:1902488
label: cholangiocyte apoptotic process
modifier: INCREASED
downstream:
- target: Hepatic fibrosis
- target: Cirrhosis
evidence:
- reference: PMID:39250501
reference_title: Central role for cholangiocyte pathobiology in cholestatic
liver diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cholangiopathies comprise a spectrum of chronic intrahepatic and
extrahepatic biliary tract disorders culminating in progressive
cholestatic liver injury, fibrosis, and often cirrhosis and its sequela.
explanation: >-
This cholangiopathy review supports progression from biliary-tract
disease to cholestatic liver injury, fibrosis, and cirrhosis.
histopathology:
- name: Periductal onion-skin fibrosis
description: >-
Concentric periductal fibrosis and fibrous obliterative cholangitis are
classic PSC-compatible histopathology findings, particularly in small-duct
or recurrent disease contexts.
phenotypes:
- category: Hepatobiliary
name: Sclerosing Cholangitis
diagnostic: true
phenotype_term:
preferred_term: Sclerosing cholangitis
term:
id: HP:0030991
label: Sclerosing cholangitis
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sclerosing cholangitis (SC) is defined as a condition with progressive
stenosis and destruction of the bile ducts due to diffuse inflammation
and fibrosis and currently includes three categories: primary sclerosing
cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing
cholangitis (IgG4-SC).
explanation: >-
The abstract definition supports sclerosing cholangitis as the diagnostic
phenotype of the root disorder.
- category: Hepatobiliary
name: Cholestasis
phenotype_term:
preferred_term: Cholestasis
term:
id: HP:0001396
label: Cholestasis
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
SC categories share similar clinical features, such as cholestasis.
explanation: >-
This review supports cholestasis as a shared clinical feature across
sclerosing cholangitis categories.
- category: Hepatobiliary
name: Jaundice
phenotype_term:
preferred_term: Jaundice
term:
id: HP:0000952
label: Jaundice
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients with SC present with cholestatic symptoms, including jaundice and
pruritus, and blood tests reveal elevation of cholestatic enzymes.
explanation: >-
This directly supports jaundice as a cholestatic symptom of sclerosing
cholangitis.
- category: Dermatological
name: Pruritus
phenotype_term:
preferred_term: Pruritus
term:
id: HP:0000989
label: Pruritus
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients with SC present with cholestatic symptoms, including jaundice and
pruritus, and blood tests reveal elevation of cholestatic enzymes.
explanation: >-
This directly supports pruritus as a cholestatic symptom of sclerosing
cholangitis.
- category: Systemic
name: Fatigue
description: >-
Fatigue is a common patient-reported symptom in PSC-focused clinical
summaries and is included here without a frequency claim because the cached
abstracts do not provide a direct quantitative quote.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Gastrointestinal
name: Abdominal pain
description: >-
Abdominal pain can occur in symptomatic sclerosing cholangitis and
cholangitis episodes; no frequency is asserted from the cached abstracts.
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
- category: Laboratory
name: Elevated alkaline phosphatase
diagnostic: true
phenotype_term:
preferred_term: Elevated circulating alkaline phosphatase concentration
term:
id: HP:0003155
label: Elevated circulating alkaline phosphatase concentration
evidence:
- reference: DOI:10.1007/s00535-025-02265-5
reference_title: The 2024 diagnostic criteria for primary sclerosing
cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
As there were no specific biomarkers for diagnosing PSC, we developed
diagnostic criteria in 2016 based on cholangiography and elevated biliary
enzymes.
explanation: >-
Supports elevated cholestatic/biliary enzymes as part of PSC diagnostic
criteria; alkaline phosphatase is modeled as the best HPO-bound
cholestatic enzyme phenotype.
- category: Laboratory
name: Elevated gamma-glutamyl transferase
diagnostic: true
phenotype_term:
preferred_term: Elevated gamma-glutamyl transferase
evidence:
- reference: DOI:10.1007/s00535-025-02265-5
reference_title: The 2024 diagnostic criteria for primary sclerosing
cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The 2024 diagnostic criteria facilitate the use of magnetic resonance
cholangiography in addition to endoscopic retrograde cholangiography in
imaging, and incorporate gamma-glutamyl transferase for evaluating
cholestasis to diagnose pediatric patients.
explanation: >-
Supports GGT as a diagnostic cholestasis measure. The review-suggested
HP:0003285 binding is not present in the local HPO cache, so this keeps a
preferred-term-only descriptor.
- category: Hepatobiliary
name: Hepatic fibrosis
phenotype_term:
preferred_term: Hepatic fibrosis
term:
id: HP:0001395
label: Hepatic fibrosis
evidence:
- reference: PMID:39250501
reference_title: Central role for cholangiocyte pathobiology in cholestatic
liver diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cholangiopathies comprise a spectrum of chronic intrahepatic and
extrahepatic biliary tract disorders culminating in progressive
cholestatic liver injury, fibrosis, and often cirrhosis and its sequela.
explanation: >-
Supports hepatic fibrosis as a central downstream consequence of
cholangiopathies including sclerosing cholangitis.
- category: Hepatobiliary
name: Cirrhosis
phenotype_term:
preferred_term: Cirrhosis
term:
id: HP:0001394
label: Cirrhosis
evidence:
- reference: PMID:39250501
reference_title: Central role for cholangiocyte pathobiology in cholestatic
liver diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cholangiopathies comprise a spectrum of chronic intrahepatic and
extrahepatic biliary tract disorders culminating in progressive
cholestatic liver injury, fibrosis, and often cirrhosis and its sequela.
explanation: >-
Supports cirrhosis as an advanced outcome of chronic cholangiopathy.
biochemical:
- name: Cholestatic Enzymes
presence: Elevated
context: Blood tests show a cholestatic pattern in clinically apparent
disease.
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients with SC present with cholestatic symptoms, including jaundice and
pruritus, and blood tests reveal elevation of cholestatic enzymes.
explanation: >-
Supports elevated cholestatic enzymes as a shared biochemical feature.
- name: Alkaline Phosphatase
presence: Elevated
context: Adult cholestatic diagnostic pattern.
- name: Gamma-Glutamyl Transferase
presence: Elevated
context: Pediatric and cholestasis-focused diagnostic pattern.
environmental:
- name: Inflammatory bowel disease comorbidity context
description: >-
IBD is not modeled in a dedicated comorbidities slot because the current
Disease schema has no such top-level slot, but the PSC-IBD association is a
major clinical context for sclerosing cholangitis.
evidence:
- reference: DOI:10.1136/gutjnl-2023-330856
reference_title: Protective function of sclerosing cholangitis on IBD
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
There is a strong clinical association between IBD and primary sclerosing
cholangitis (PSC), a chronic disease of the liver characterised by
biliary inflammation that leads to strictures and fibrosis.
explanation: >-
Supports IBD as a major clinical association/comorbidity context for PSC
within the sclerosing cholangitis umbrella.
diagnosis:
- name: Cholangiographic Stricture Pattern
description: >-
Diagnosis depends on recognizing intrahepatic and/or extrahepatic bile-duct
strictures and then distinguishing primary, secondary, IgG4-related, and
neonatal etiologies using clinical context, serology, histology, and
exclusion of mimics.
results: Multifocal or segmental biliary stenosis with evidence of
cholestasis.
evidence:
- reference: PMID:27625195
reference_title: "IgG4-related hepatobiliary disease: an overview."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
These diseases can present with biliary strictures and/or mass lesions,
making them difficult to differentiate from primary sclerosing
cholangitis (PSC) or other hepatobiliary malignancies.
explanation: >-
This supports biliary strictures as a diagnostic presentation and
highlights the need to distinguish sclerosing cholangitis subtypes and
malignancy mimics.
- name: Endoscopic or Magnetic Cholangiography
description: >-
MRCP and ERCP are used to document characteristic biliary strictures and
support subtype-level diagnosis.
diagnosis_term:
preferred_term: endoscopic retrograde cholangiopancreatography
term:
id: MAXO:0035049
label: endoscopic retrograde cholangiopancreatography
evidence:
- reference: PMID:30205418
reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing
Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cholangiography, endoscopic or magnetic, is inevitably required for
making a diagnosis.
explanation: >-
Supports cholangiography as required diagnostic imaging for sclerosing
cholangitis.
treatments:
- name: Etiology-Directed Management
description: >-
Treatment depends on the subtype and cause: IgG4-related disease is often
immunosuppression-responsive, dominant strictures may need endoscopic
management, secondary forms require treatment of the inciting injury, and
advanced disease can require liver transplantation.
- name: Liver Transplantation
description: >-
Liver transplantation is used for end-stage or otherwise advanced
sclerosing cholangitis when progressive liver failure or complications
cannot be controlled.
treatment_term:
preferred_term: liver transplantation
term:
id: MAXO:0001175
label: liver transplantation
target_phenotypes:
- preferred_term: Cirrhosis
term:
id: HP:0001394
label: Cirrhosis
evidence:
- reference: DOI:10.3390/jcm15031149
reference_title: Primary Sclerosing Cholangitis in 2026
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Most patients eventually require liver transplantation or develop serious
complications, the most severe being end-stage liver disease and
cholangiocarcinoma.
explanation: >-
Supports liver transplantation as a major advanced-disease treatment
endpoint in PSC.
- name: ERCP-Based Stricture Management
description: >-
ERCP can be used diagnostically and therapeutically in dominant or clinically
relevant strictures, including dilation or stenting when appropriate.
treatment_term:
preferred_term: endoscopic retrograde cholangiopancreatography
term:
id: MAXO:0035049
label: endoscopic retrograde cholangiopancreatography
target_mechanisms:
- target: Bile Duct Fibrostenosis
treatment_effect: MODULATES
description: Endoscopic therapy mechanically addresses dominant strictures.
evidence:
- reference: DOI:10.1007/s00535-025-02265-5
reference_title: The 2024 diagnostic criteria for primary sclerosing
cholangitis
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The 2024 diagnostic criteria facilitate the use of magnetic resonance
cholangiography in addition to endoscopic retrograde cholangiography in
imaging, and incorporate gamma-glutamyl transferase for evaluating
cholestasis to diagnose pediatric patients.
explanation: >-
Supports ERCP as a core procedure in PSC evaluation; the therapeutic
dilation/stenting role is retained in the description without a stronger
abstract-level quote.
- name: norUrsodeoxycholic Acid
description: >-
norUDCA is an investigational bile-acid therapy in phase 3 testing for PSC.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
target_mechanisms:
- target: Bile Acid Signaling Dysregulation
treatment_effect: MODULATES
description: norUDCA targets bile-acid biology and cholestatic injury.
evidence:
- reference: clinicaltrials:NCT03872921
reference_title: Double-blind, Randomized, Placebo-controlled, Phase III
Study Comparing norUrsodeoxycholic Acid Capsules With Placebo in the
Treatment of Primary Sclerosing Cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Double-blind, randomized, multi-center, placebo-controlled, comparative,
phase III trial. The study will be conducted with two treatment groups in
the form of a parallel group comparison and will serve to compare oral
treatment with either 1500 mg/d norursodeoxycholic acid capsules or
placebo capsules for the treatment of Primary Sclerosing Cholangitis.
explanation: >-
Supports norUDCA as an investigational PSC pharmacotherapy in a phase 3
randomized trial.
- name: Fecal Microbiota Transplantation
description: >-
FMT is an investigational gut-microbiome-directed intervention for PSC,
particularly in PSC with concomitant IBD.
treatment_term:
preferred_term: fecal microbiota transplantation
term:
id: MAXO:0000748
label: fecal microbiota transplantation
target_mechanisms:
- target: Gut-Liver Axis Barrier Disruption and Dysbiosis
treatment_effect: MODULATES
description: FMT aims to alter gut microbiota contributing to PSC biology.
evidence:
- reference: clinicaltrials:NCT02424175
reference_title: Fecal Microbiota Transplantation for the Treatment of
Primary Sclerosing Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This is an open-label single-arm pilot study to measure the safety,
microbiological and clinical impacts of Fecal Microbiota Transplantation
(FMT) in patients with Primary Sclerosing Cholangitis (PSC).
explanation: >-
Supports FMT as an investigational microbiome-directed intervention in
PSC.
clinical_trials:
- name: NCT03872921
phase: PHASE_III
description: >-
Randomized placebo-controlled phase 3 norUDCA trial in primary sclerosing
cholangitis.
evidence:
- reference: clinicaltrials:NCT03872921
reference_title: Double-blind, Randomized, Placebo-controlled, Phase III
Study Comparing norUrsodeoxycholic Acid Capsules With Placebo in the
Treatment of Primary Sclerosing Cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Double-blind, randomized, multi-center, placebo-controlled, comparative,
phase III trial.
explanation: >-
Supports this as a phase 3 PSC norUDCA clinical trial.
- name: NCT02424175
description: >-
Open-label pilot FMT study in PSC patients, including patients with
concurrent inflammatory bowel disease.
evidence:
- reference: clinicaltrials:NCT02424175
reference_title: Fecal Microbiota Transplantation for the Treatment of
Primary Sclerosing Cholangitis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This is an open-label single-arm pilot study to measure the safety,
microbiological and clinical impacts of Fecal Microbiota Transplantation
(FMT) in patients with Primary Sclerosing Cholangitis (PSC).
explanation: >-
Supports this as an FMT pilot study in PSC.
- name: NCT06286709
phase: PHASE_II
description: >-
FARGO randomized phase IIa multicenter placebo-controlled FMT trial in PSC
with concomitant IBD.
evidence:
- reference: clinicaltrials:NCT06286709
reference_title: "FARGO: A Randomised, Phase IIa, Multi-centre, Placebo-controlled
Trial of FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
FARGO is a randomised, phase IIa, multi-centre, placebo-controlled trial
to compare Faecal Microbiota Transplant (FMT) with placebo in patients
with primary sclerosing cholangitis (PSC) and concomitant inflammatory
bowel disease.
explanation: >-
Supports this as a phase 2 randomized FMT trial in PSC-IBD.
references:
- reference: DOI:10.5009/gnl18085
title: IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
findings: []
- reference: DOI:10.1097/hep.0000000000001093
title: Central role for cholangiocyte pathobiology in cholestatic liver
diseases
findings: []
- reference: DOI:10.1007/s00261-022-03551-z
title: 'Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: 'Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis'
supporting_text: 'Secondary sclerosing cholangitis: mimics of primary sclerosing
cholangitis'
- reference: DOI:10.1007/s00535-025-02265-5
title: The 2024 diagnostic criteria for primary sclerosing cholangitis
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Primary sclerosing cholangitis (PSC) is an idiopathic chronic
cholestatic disease with a poor prognosis.
supporting_text: Primary sclerosing cholangitis (PSC) is an idiopathic
chronic cholestatic disease with a poor prognosis.
evidence:
- reference: DOI:10.1007/s00535-025-02265-5
reference_title: The 2024 diagnostic criteria for primary sclerosing
cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Primary sclerosing cholangitis (PSC) is an idiopathic chronic
cholestatic disease with a poor prognosis.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.1007/s00535-026-02388-3
title: Distinct phenotype of primary sclerosing cholangitis-associated
inflammatory bowel disease
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Primary sclerosing cholangitis (PSC) is frequently accompanied by
colitis with clinicopathologic features that differ from conventional
inflammatory bowel disease (IBD).
supporting_text: Primary sclerosing cholangitis (PSC) is frequently
accompanied by colitis with clinicopathologic features that differ from
conventional inflammatory bowel disease (IBD).
evidence:
- reference: DOI:10.1007/s00535-026-02388-3
reference_title: Distinct phenotype of primary sclerosing
cholangitis-associated inflammatory bowel disease
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Primary sclerosing cholangitis (PSC) is frequently accompanied by
colitis with clinicopathologic features that differ from conventional
inflammatory bowel disease (IBD).
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.1007/s12072-023-10521-0
title: 'Hepatobiliary long-term consequences of COVID-19: dramatically increased
rate of secondary sclerosing cholangitis in critically ill COVID-19 patients'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Increasing evidence suggests that secondary sclerosing
cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a
hepatobiliary long-term complication of COVID-19.
supporting_text: Increasing evidence suggests that secondary sclerosing
cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a
hepatobiliary long-term complication of COVID-19.
evidence:
- reference: DOI:10.1007/s12072-023-10521-0
reference_title: 'Hepatobiliary long-term consequences of COVID-19: dramatically
increased rate of secondary sclerosing cholangitis in critically ill COVID-19
patients'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Increasing evidence suggests that secondary sclerosing
cholangitis (SSC), which can lead to cirrhosis or liver failure, may be
a hepatobiliary long-term complication of COVID-19.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.1016/j.jhepr.2024.101272
title: 'Primary sclerosing cholangitis–inflammatory bowel disease: Epidemiology,
mortality, and impact of diagnostic sequence'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: 'Primary sclerosing cholangitis–inflammatory bowel disease: Epidemiology,
mortality, and impact of diagnostic sequence'
supporting_text: 'Primary sclerosing cholangitis–inflammatory bowel disease: Epidemiology,
mortality, and impact of diagnostic sequence'
- reference: DOI:10.1016/j.lanepe.2024.101002
title: 'Past, current, and future trends in the prevalence of primary sclerosing
cholangitis and inflammatory bowel disease across England (2015–2027): a nationwide,
population-based study'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: 'Past, current, and future trends in the prevalence of primary sclerosing
cholangitis and inflammatory bowel disease across England (2015–2027): a nationwide,
population-based study'
supporting_text: 'Past, current, and future trends in the prevalence of primary
sclerosing cholangitis and inflammatory bowel disease across England (2015–2027):
a nationwide, population-based study'
- reference: DOI:10.1093/ecco-jcc/jjae096
title: Inflammatory Bowel Disease Associated with Primary Sclerosing
Cholangitis is Associated with an Altered Gut Microbiome and Bile Acid
Profile
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Primary sclerosing cholangitis associated with inflammatory bowel
disease [IBD-PSC] carries significant morbidity compared to IBD without
PSC.
supporting_text: Primary sclerosing cholangitis associated with inflammatory
bowel disease [IBD-PSC] carries significant morbidity compared to IBD
without PSC.
evidence:
- reference: DOI:10.1093/ecco-jcc/jjae096
reference_title: Inflammatory Bowel Disease Associated with Primary
Sclerosing Cholangitis is Associated with an Altered Gut Microbiome and
Bile Acid Profile
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Primary sclerosing cholangitis associated with inflammatory bowel
disease [IBD-PSC] carries significant morbidity compared to IBD without
PSC.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.1111/j.1478-3231.2011.02484.x
title: 'Validity of administrative data for the diagnosis of primary sclerosing
cholangitis: a population-based study'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: 'Validity of administrative data for the diagnosis of primary sclerosing
cholangitis: a population-based study'
supporting_text: 'Validity of administrative data for the diagnosis of primary
sclerosing cholangitis: a population-based study'
- reference: DOI:10.1136/gutjnl-2023-330856
title: Protective function of sclerosing cholangitis on IBD
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: There is a strong clinical association between IBD and primary
sclerosing cholangitis (PSC), a chronic disease of the liver characterised
by biliary inflammation that leads to strictures and fibrosis.
supporting_text: There is a strong clinical association between IBD and
primary sclerosing cholangitis (PSC), a chronic disease of the liver
characterised by biliary inflammation that leads to strictures and
fibrosis.
evidence:
- reference: DOI:10.1136/gutjnl-2023-330856
reference_title: Protective function of sclerosing cholangitis on IBD
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: There is a strong clinical association between IBD and primary
sclerosing cholangitis (PSC), a chronic disease of the liver
characterised by biliary inflammation that leads to strictures and
fibrosis.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.1186/s12876-024-03162-6
title: 'Investigating the shared genetic architecture between primary sclerosing
cholangitis and inflammatory bowel diseases: a Mendelian randomization study'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Several studies have found that primary sclerosing cholangitis
(PSC) and inflammatory bowel disease (IBD) are closely associated.
supporting_text: Several studies have found that primary sclerosing
cholangitis (PSC) and inflammatory bowel disease (IBD) are closely
associated.
evidence:
- reference: DOI:10.1186/s12876-024-03162-6
reference_title: 'Investigating the shared genetic architecture between primary
sclerosing cholangitis and inflammatory bowel diseases: a Mendelian randomization
study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Several studies have found that primary sclerosing cholangitis
(PSC) and inflammatory bowel disease (IBD) are closely associated.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.15403/jgld-5476
title: 'Endoscopic Characterization and Outcome of COVID-19 Patients with Secondary
Sclerosing Cholangitis: A Case Series of a Tertiary Center'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: 'Endoscopic Characterization and Outcome of COVID-19 Patients with
Secondary Sclerosing Cholangitis: A Case Series of a Tertiary Center'
supporting_text: During the coronavirus disease 2019 (COVID-19) pandemic a
significant proportion of patients with severe acute respiratory
distress syndrome (ARDS) due to COVID-19 infection developed secondary
sclerosing cholangitis (SSC) as a hepatobiliary complication.
evidence:
- reference: DOI:10.15403/jgld-5476
reference_title: 'Endoscopic Characterization and Outcome of COVID-19 Patients
with Secondary Sclerosing Cholangitis: A Case Series of a Tertiary Center'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: During the coronavirus disease 2019 (COVID-19) pandemic a
significant proportion of patients with severe acute respiratory
distress syndrome (ARDS) due to COVID-19 infection developed secondary
sclerosing cholangitis (SSC) as a hepatobiliary complication.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.2147/hmer.s384220
title: 'Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific
Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill
Patients?'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: 'Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use
or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia
in Critically Ill Patients?'
supporting_text: 'Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine
Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia
in Critically Ill Patients?'
- reference: DOI:10.3390/cancers17132165
title: Navigating Neoplasm Risk in Inflammatory Bowel Disease and Primary
Sclerosing Cholangitis
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Navigating Neoplasm Risk in Inflammatory Bowel Disease and
Primary Sclerosing Cholangitis
supporting_text: (1) Background and Patients with inflammatory bowel disease
(IBD) and primary sclerosing cholangitis (PSC) face a significantly
increased risk of malignancies, including a 10-fold higher risk for
colorectal cancer (CRC) and a lifetime risk for cholangiocarcinoma (CCA)
exceeding 20%.
evidence:
- reference: DOI:10.3390/cancers17132165
reference_title: Navigating Neoplasm Risk in Inflammatory Bowel Disease
and Primary Sclerosing Cholangitis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: (1) Background and Patients with inflammatory bowel disease (IBD)
and primary sclerosing cholangitis (PSC) face a significantly increased
risk of malignancies, including a 10-fold higher risk for colorectal
cancer (CRC) and a lifetime risk for cholangiocarcinoma (CCA) exceeding
20%.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.3390/cells13191650
title: 'Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape
and Future Developments'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Primary sclerosing cholangitis (PSC) is a rare, chronic liver
disease with no approved therapies.
supporting_text: Primary sclerosing cholangitis (PSC) is a rare, chronic
liver disease with no approved therapies.
evidence:
- reference: DOI:10.3390/cells13191650
reference_title: 'Bile Acids-Based Therapies for Primary Sclerosing Cholangitis:
Current Landscape and Future Developments'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Primary sclerosing cholangitis (PSC) is a rare, chronic liver
disease with no approved therapies.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.3390/jcm14217817
title: 'Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response in Pathogenesis
of Primary Sclerosing Cholangitis: An Overview'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Primary sclerosing cholangitis (PSC) is a chronic,
immune-mediated cholestatic liver disease characterized by progressive
bile duct inflammation and fibrosis.
supporting_text: Primary sclerosing cholangitis (PSC) is a chronic,
immune-mediated cholestatic liver disease characterized by progressive
bile duct inflammation and fibrosis.
evidence:
- reference: DOI:10.3390/jcm14217817
reference_title: 'Gut–Liver Axis, Microbiota, Bile Acids, and Immune Response
in Pathogenesis of Primary Sclerosing Cholangitis: An Overview'
supports: SUPPORT
evidence_source: OTHER
snippet: Primary sclerosing cholangitis (PSC) is a chronic,
immune-mediated cholestatic liver disease characterized by progressive
bile duct inflammation and fibrosis.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.3390/jcm15031149
title: 'Primary Sclerosing Cholangitis: Diagnosis, Management, and Clinical Challenges'
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Primary sclerosing cholangitis is a rare, chronic, inflammatory
disease of the biliary tree that leads to progressive ductal obliteration,
hepatic dysfunction, and ultimately liver cirrhosis.
supporting_text: Primary sclerosing cholangitis is a rare, chronic,
inflammatory disease of the biliary tree that leads to progressive ductal
obliteration, hepatic dysfunction, and ultimately liver cirrhosis.
evidence:
- reference: DOI:10.3390/jcm15031149
reference_title: 'Primary Sclerosing Cholangitis: Diagnosis, Management, and
Clinical Challenges'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Primary sclerosing cholangitis is a rare, chronic, inflammatory
disease of the biliary tree that leads to progressive ductal
obliteration, hepatic dysfunction, and ultimately liver cirrhosis.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
- reference: DOI:10.4103/eus-d-22-00208
title: Secondary sclerosing cholangitis and IgG4-sclerosing cholangitis – A
review of cholangiographic and ultrasound imaging
found_in:
- Sclerosing_Cholangitis-deep-research-falcon.md
findings:
- statement: Sclerosing cholangitis (SC) represents a spectrum of chronic
progressive cholestatic diseases of the intrahepatic and/or extrahepatic
biliary system characterized by patchy inflammation, fibrosis, and
stricturing.
supporting_text: Sclerosing cholangitis (SC) represents a spectrum of
chronic progressive cholestatic diseases of the intrahepatic and/or
extrahepatic biliary system characterized by patchy inflammation,
fibrosis, and stricturing.
evidence:
- reference: DOI:10.4103/eus-d-22-00208
reference_title: Secondary sclerosing cholangitis and IgG4-sclerosing
cholangitis – A review of cholangiographic and ultrasound imaging
supports: SUPPORT
evidence_source: OTHER
snippet: Sclerosing cholangitis (SC) represents a spectrum of chronic
progressive cholestatic diseases of the intrahepatic and/or extrahepatic
biliary system characterized by patchy inflammation, fibrosis, and
stricturing.
explanation: Deep research cited this publication as relevant literature
for Sclerosing Cholangitis.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Sclerosing Cholangitis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Sclerosing cholangitis is a spectrum of chronic progressive cholestatic biliary diseases characterized by patchy bile-duct inflammation, fibrosis, and stricturing; it is classified as primary (PSC; no identifiable cause) or secondary (SSC; attributable to a specific insult such as ischemia, infection, toxins/drugs, or immune-mediated conditions including IgG4-related disease). (ludwig2023secondarysclerosingcholangitis pages 1-3, moller2023secondarysclerosingcholangitis pages 1-2)
PSC is strongly linked to inflammatory bowel disease (IBD) (commonly ulcerative colitis) and carries substantial risks of cirrhosis, need for liver transplantation, and hepatobiliary/colorectal malignancies. (crothers2024pastcurrentand pages 1-2, pitoni2025navigatingneoplasmrisk pages 1-2)
In 2023–2024, major advances include: (i) new population-based epidemiology showing increasing PSC-IBD prevalence with projections to 2027 in England; (ii) microbiome + bile-acid multi-omic profiling that quantifies functional changes in secondary bile acid metabolism in PSC-IBD; and (iii) expanding clinical trial portfolios emphasizing ALP-based endpoints, noninvasive fibrosis measures, and patient-reported outcomes (PROs). (crothers2024pastcurrentand pages 1-2, leibovitzh2024inflammatoryboweldisease pages 1-2, NCT03872921 chunk 1)
| Entity/scope | Common synonyms | MeSH ID/term | MONDO/EFO | Key distinguishing feature |
|---|---|---|---|---|
| Sclerosing cholangitis (umbrella entity) | SC; cholangitis, sclerosing | D015209 / Cholangitis, Sclerosing | EFO_0004268 (sclerosing cholangitis) | Chronic cholestatic biliary disease spectrum with inflammation, fibrosis, stricturing, and beading of intrahepatic and/or extrahepatic bile ducts; includes primary and secondary forms. ICD codes: not extracted from the provided sources. Identifier note: limited to retrieved evidence. (ludwig2023secondarysclerosingcholangitis pages 1-3, moller2023secondarysclerosingcholangitis pages 1-2, OpenTargets Search: primary sclerosing cholangitis, NCT02424175 chunk 2) |
| Primary sclerosing cholangitis (PSC) | PSC; large-duct PSC; small-duct PSC | D015209 / Cholangitis, Sclerosing | No PSC-specific MONDO/EFO identifier extracted from the provided sources; umbrella mapping available as EFO_0004268 | Diagnosed when characteristic cholangiographic multifocal short strictures/beading are present without another identifiable cause; small-duct PSC has normal cholangiography but PSC-consistent histology. Strong association with IBD. ICD codes: not extracted from the provided sources. Identifier note: limited to retrieved evidence. (naitoh2025the2024diagnostic pages 4-5, ludwig2023secondarysclerosingcholangitis pages 1-3, giorgio2026primarysclerosingcholangitis pages 2-4, naitoh2025the2024diagnostic media a72fe8f4) |
| Secondary sclerosing cholangitis (SSC) | SSC; ischemic cholangiopathy; SSC-CIP; COVID-19 SSC / SSC-COVID | D015209 / Cholangitis, Sclerosing | No SSC-specific MONDO/EFO identifier extracted from the provided sources; umbrella mapping available as EFO_0004268 | PSC mimic with an identifiable cause such as ischemic, infectious, toxic/drug-induced, immunologic, congenital, or critical-illness-related injury; often worse prognosis, with biliary casts common in SSC-CIP/COVID-19 SSC. ICD codes: not extracted from the provided sources. Identifier note: limited to retrieved evidence. (ludwig2023secondarysclerosingcholangitis pages 3-4, ludwig2023secondarysclerosingcholangitis pages 7-9, hofstetter2024endoscopiccharacterizationand pages 6-7, leonhardt2023hepatobiliarylongtermconsequences pages 1-2) |
| IgG4-related sclerosing cholangitis (IgG4-SC) | IgG4-SC; IgG4-related SC; IgG4-related cholangitis | D015209 / Cholangitis, Sclerosing | No IgG4-SC-specific MONDO/EFO identifier extracted from the provided sources | Immune-mediated biliary manifestation of IgG4-related disease; typically long-segment continuous extrahepatic strictures with bile duct wall thickening, elevated serum IgG4 in many patients, frequent autoimmune pancreatitis overlap, and marked corticosteroid responsiveness. ICD codes: not extracted from the provided sources. Identifier note: limited to retrieved evidence. (ludwig2023secondarysclerosingcholangitis pages 7-9, moller2023secondarysclerosingcholangitis pages 8-10, moller2023secondarysclerosingcholangitis pages 10-11) |
| Hepatobiliary malignancy complication relevant to PSC surveillance | Cholangiocarcinoma; adenocarcinoma of gallbladder and extrahepatic biliary tract | Not extracted from the provided sources | MONDO_0018536 (adenocarcinoma of gallbladder and extrahepatic biliary tract) | Included here because malignancy surveillance is central in PSC/PSC-IBD; this is a complication/comorbidity rather than a synonym of sclerosing cholangitis. Identifier note: limited to retrieved evidence. (giorgio2026primarysclerosingcholangitis pages 7-9, OpenTargets Search: primary sclerosing cholangitis,secondary sclerosing cholangitis) |
Table: This table summarizes the identifiers and common names available in the retrieved evidence for the sclerosing cholangitis disease family, emphasizing PSC, SSC, and IgG4-SC. It is useful for knowledge-base normalization while explicitly flagging where ICD or subtype-specific ontology identifiers were not available from the provided sources.
Important limitation: This tool-based review did not retrieve PSC-specific MONDO/Orphanet/OMIM identifiers. The OpenTargets/ontology mapping available in retrieved evidence covers the umbrella term “sclerosing cholangitis” (EFO_0004268) rather than PSC subtype-specific ontologies. (OpenTargets Search: primary sclerosing cholangitis)
PSC has historically lacked a distinct ICD code and is frequently coded under ICD-10 K83.0 (“cholangitis”), which also includes more common acute entities (e.g., ascending cholangitis), lowering specificity for true PSC ascertainment. (molodecky2011validityofadministrative pages 1-2)
In ICD-10-CA (Canadian modification), PSC and SSC appear as subcodes under K83.0: K83.00 primary sclerosing cholangitis and K83.01 secondary sclerosing cholangitis, alongside K83.02 ascending cholangitis. (molodecky2011validityofadministrative pages 7-8)
Evidence in this report is predominantly aggregated disease-level research: population-based registries (England, Ontario), prospective registries, clinical series, and interventional trial registries; individual-patient evidence is present mainly as clinical case series (e.g., COVID-19 SSC) and pilot trials. (crothers2024pastcurrentand pages 1-2, leung2025primarysclerosingcholangitis–inflammatory pages 1-2, hofstetter2024endoscopiccharacterizationand pages 1-2)
PSC is best supported as a complex, immune-mediated, polygenic disease in which genetic susceptibility (strong HLA signal plus many non-HLA loci) interacts with gut–liver axis biology (microbiome, bile acids, mucosal immunity) to drive chronic cholangiocyte injury and periductal fibrosis. (fiorucci2024bileacidsbasedtherapies pages 2-4, okada2026distinctphenotypeof pages 5-7)
SSC is etiologically heterogeneous and arises from identifiable insults (e.g., ischemic cholangiopathy/critical illness, infection, toxins/drugs, immunologic disorders). (ludwig2023secondarysclerosingcholangitis pages 7-9, moller2023secondarysclerosingcholangitis pages 1-2)
Authoritative target-disease association resources (OpenTargets) also prioritize immune-related genes including IL2RA, SH2B3, BACH2, IRF5, IL10 for “sclerosing cholangitis,” consistent with immune genetic architecture. (OpenTargets Search: primary sclerosing cholangitis)
Robust, generalizable protective factors for PSC are not established. However, mechanistic and translational evidence suggests microbiome-driven induction of regulatory pathways may modulate gut inflammation in PSC-IBD contexts; in experimental models, sclerosing cholangitis altered microbiota and increased Foxp3+ Treg expansion with attenuation of colitis. (bedke2024protectivefunctionof pages 1-2)
A contemporary synthesis links genetic susceptibility, bile-acid dysregulation, and microbiome perturbations: PSC-IBD patients show dysfunctional bile-acid metabolism and altered microbial conversion of secondary bile acids, and lymphocyte trafficking pathways (e.g., α4β7/MAdCAM-1) integrate gut-derived antigenic stimulation with hepatic biliary inflammation. (pitoni2025navigatingneoplasmrisk pages 5-7, fiorucci2024bileacidsbasedtherapies pages 2-4)
Symptoms/signs (typical, variable; adult-onset common) * Common cholestatic symptom cluster: abdominal pain, pruritus, and fatigue reported in ~three-quarters of patients in a recent clinical review; fever with these suggests acute bacterial cholangitis. (giorgio2026primarysclerosingcholangitis pages 2-4) * Depressive-type symptoms reported in ~one-quarter of patients in the same review. (giorgio2026primarysclerosingcholangitis pages 2-4)
Laboratory abnormalities * Typical cholestatic pattern: elevated ALP and GGT; bilirubin elevated in ~28–40% (rising with progression), but ~25% may have normal liver tests. (giorgio2026primarysclerosingcholangitis pages 2-4)
Imaging features * Hallmark cholangiography findings: multifocal beading/strictures with bile duct wall thickening/enhancement; peripheral pruning in chronic disease. (ludwig2023secondarysclerosingcholangitis pages 1-3)
Dominant/clinically relevant strictures * Dominant stricture definitions incorporate radiologic stenosis and/or biochemical and symptom criteria; ERCP-based criteria may include difficulty passing >5 Fr catheter, and improvement (~20% ALP/bilirubin at 2–4 weeks) after dilation/stenting is used as supportive evidence. (giorgio2026primarysclerosingcholangitis pages 2-4)
PSC-associated IBD often has a distinct phenotype: extensive colitis with right-sided predominance, rectal sparing, and backwash ileitis; disease may be clinically mild/asymptomatic despite extensive involvement, but neoplasia risk is high, motivating early intensive surveillance. (okada2026distinctphenotypeof pages 1-2)
COVID-19 SSC and SSC-CIP often present with cholestatic enzymes and characteristic cholangiographic findings including biliary casts and intrahepatic duct destruction/rarefaction. In one tertiary center case series, all ERCPs revealed biliary casts, with severe intrahepatic duct rarefication in 9/17. (hofstetter2024endoscopiccharacterizationand pages 1-2)
(These are ontology suggestions; phenotype-to-HPO mappings were not explicitly provided in retrieved sources.) * Pruritus HP:0000989 * Fatigue HP:0012378 * Abdominal pain HP:0002027 * Cholestasis HP:0001396 * Elevated alkaline phosphatase HP:0003155 * Elevated gamma-glutamyltransferase HP:0003285 * Hyperbilirubinemia HP:0002904 * Cholangitis HP:0006565 * Biliary strictures HP:0031377 (term may vary by HPO version) * Liver fibrosis HP:0001395 * Cirrhosis HP:0001394
PSC is typically not monogenic; current evidence supports polygenic susceptibility dominated by HLA associations and multiple immune-regulatory loci rather than single causal variants. (fiorucci2024bileacidsbasedtherapies pages 2-4)
Susceptibility loci and associated pathways cluster around: T-cell activation/co-stimulation (e.g., CD28/CTLA4 axis), cytokine signaling (IL2RA), innate immune regulation (NFKB1), and gut barrier/bile-acid signaling (e.g., GPBAR1/TGR5, GPR35). (fiorucci2024bileacidsbasedtherapies pages 2-4)
ClinVar/gnomAD-level variant cataloging (ACMG/AMP classification, allele frequencies) was not available in retrieved sources for PSC; therefore specific pathogenic variant nomenclature and population frequencies cannot be reliably populated from the current evidence set.
Epigenetic mechanisms are implicated in reviews of PSC pathogenesis, but explicit methylation/histone datasets were not extracted in this tool run.
In SSC-CIP associated with severe COVID-19, mechanisms considered include direct cholangiocyte injury (ACE2 expression in cholangiocytes is discussed in reviews) plus ischemic and microthrombotic injury; causality of direct viral damage versus critical-illness-associated ischemia remains debated. (bartoli2023secondarysclerosingcholangitis pages 1-2, leonhardt2023hepatobiliarylongtermconsequences pages 12-13)
No consistent lifestyle risk/protective factors for PSC were extracted in retrieved sources.
A convergent model supported by recent authoritative reviews describes PSC as a gut–liver axis disorder: 1) Barrier dysfunction and dysbiosis allow microbial products/metabolites to reach portal circulation (leaky gut). (fousekis2025gut–liveraxismicrobiota pages 2-4) 2) Innate immune activation in the liver (Kupffer cells, sinusoidal endothelium, cholangiocytes) triggers inflammatory pathways including NF-κB and inflammasome signaling with pro-inflammatory cytokine production (e.g., IL-6, IL-1β, TNF-α). (fiorucci2024bileacidsbasedtherapies pages 2-4, fousekis2025gut–liveraxismicrobiota pages 2-4) 3) Adaptive immune recruitment and trafficking: mucosal homing pathways (MAdCAM-1/α4β7, CCR9/CCL25, VAP-1) misdirect gut-primed lymphocytes to the liver and biliary tree, sustaining antigen-driven cholangiocyte injury. (fiorucci2024bileacidsbasedtherapies pages 2-4, fousekis2025gut–liveraxismicrobiota pages 10-11) 4) Cholangiocyte activation and fibrosis: injured cholangiocytes produce pro-inflammatory and pro-fibrotic mediators (TNFα, IL-6, MCP-1, TGFβ), activating hepatic stellate cells/portal fibroblasts and driving periductal fibrosis and ductular reaction. (fiorucci2024bileacidsbasedtherapies pages 2-4)
PSC shows altered bile-acid profiles (elevated serum primary/conjugated bile acids; reduced secondary bile acids; increased primary:secondary ratio) and dysregulated bile-acid receptor signaling through FXR and GPBAR1/TGR5, which modulate intestinal barrier integrity, immune activation, and cholangiocyte homeostasis. (fiorucci2024bileacidsbasedtherapies pages 9-10)
In particular, TGR5 on cholangiocytes supports chloride/bicarbonate secretion (“bicarbonate umbrella”) and anti-inflammatory barrier effects; downregulation is posited to contribute to PSC. (fousekis2025gut–liveraxismicrobiota pages 7-9)
A 2024 metagenomic + bile acid mass spectrometry study (n=116; 54 IBD-PSC, 62 IBD-only) found: * Reduced microbial gene richness (p=0.004) * Significant compositional shift (PERMANOVA R2=0.01, p=0.03) * Species differences: decreased Blautia obeum; increased Veillonella atypica, Veillonella dispar, and Clostridium scindens (q<0.05) * Increased microbial gene abundance for secondary bile-acid metabolism * Serum bile-acid differences (decreased sulphated secondary bile acids; increased conjugated secondary bile acids) associated with greater liver fibrosis. (leibovitzh2024inflammatoryboweldisease pages 1-2)
PSC is generally chronic and progressive, with median transplant-free survival commonly reported as ~14–21 years from diagnosis (tertiary vs population-based settings). (crothers2024pastcurrentand pages 1-2, pitoni2025navigatingneoplasmrisk pages 1-2)
In SSC-CIP, bile duct destruction can begin within days of ICU care and progress rapidly; in COVID-19 SSC, cholangiopathy can present months after infection in reported cohorts and has poor outcomes. (hofstetter2024endoscopiccharacterizationand pages 6-7, bartoli2023secondarysclerosingcholangitis pages 7-8)
| Condition/subtype | Geography/source (with URL) | Study period | Key statistics (incidence/prevalence/AAPC or mortality/survival/HR) | Notes |
|---|---|---|---|---|
| PSC-IBD prevalence trends | England; Crothers et al. 2024, Lancet Regional Health - Europe; https://doi.org/10.1016/j.lanepe.2024.101002 | 2015–2027 forecast | Among ages 18–60, prevalence was 5.0/100,000 in 2015 (5.7 including IBD diagnosed after PSC) and 7.6/100,000 in 2020 (8.6 including subsequent IBD); AAPC 8.8% from 2015–2020; projected to reach 11.7/100,000 by 2027 (95% PI 10.8–12.7), or 13.3/100,000 including subsequent IBD; projected AAPC 6.4% (crothers2024pastcurrentand pages 1-2) | Nationwide population-based prevalence/projection study; also notes median transplant-free survival reported as 14–21 years from diagnosis (crothers2024pastcurrentand pages 1-2) |
| PSC-IBD epidemiology and outcomes | Ontario, Canada; Leung et al. 2025, JHEP Reports; https://doi.org/10.1016/j.jhepr.2024.101272 | 2002–2018 | Incidence 0.46/100,000 person-years; prevalence 5.53/100,000. About 1 PSC-IBD diagnosis per 50 new IBD diagnoses, and ~1 person with PSC-IBD per 100 people living with IBD. IBD diagnosed before PSC in 83%. Compared with IBD alone, PSC-IBD had 4.5-fold greater transplant/death risk. If IBD preceded PSC, transplant/death HR 1.34 and death HR 2.73 (leung2025primarysclerosingcholangitis–inflammatory pages 1-2) | Population-based study emphasizing diagnostic sequence; higher socioeconomic status associated with higher incidence and faster increase over time (leung2025primarysclerosingcholangitis–inflammatory pages 1-2) |
| Secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) | Berlin, Germany; Leonhardt et al. 2023, Hepatology International; https://doi.org/10.1007/s12072-023-10521-0 | COVID-19 cohort during pandemic; hospitalized patients including 1,082 ventilated cases | SSC occurred exclusively in invasively ventilated patients at 1 in 43 ventilated COVID-19 patients; 1-year transplant-free survival 40%. Additional outcome metrics reported: HR for death 3.91; median survival 5.7 vs 26.8 months; ~22% may require liver transplantation (leonhardt2023hepatobiliarylongtermconsequences pages 12-13, leonhardt2023hepatobiliarylongtermconsequences pages 1-2) | Risk factors preceding SSC-CIP included systemic hypoxia, high SOFA score, high fibrinogen, and ketamine exposure; fibrinogen and LDH were independent risk factors (leonhardt2023hepatobiliarylongtermconsequences pages 12-13, leonhardt2023hepatobiliarylongtermconsequences pages 1-2) |
| COVID-19-associated secondary sclerosing cholangitis | Single tertiary center; Hofstetter et al. 2024, Journal of Gastrointestinal and Liver Diseases; https://doi.org/10.15403/jgld-5476 | Feb 2020–Oct 2022 | Among 258 mechanically ventilated COVID-19 patients, COVID-19 SSC occurred in 2.6% (10 in-house cases; 7 referred total cohort n=17). Mortality was 14/17 (82%); 3 patients remained in follow-up for possible liver transplantation (hofstetter2024endoscopiccharacterizationand pages 1-2, hofstetter2024endoscopiccharacterizationand pages 6-7) | ERC showed biliary casts in all cases; many had severe rarefication of intrahepatic ducts (9/17) and strictures (4/17). Endoscopic therapy was used as a bridge to transplant but recurrence was common (hofstetter2024endoscopiccharacterizationand pages 1-2, hofstetter2024endoscopiccharacterizationand pages 6-7) |
Table: This table summarizes recent population-based and clinical outcome data for PSC/PSC-IBD and SSC-CIP, highlighting prevalence trends, incidence, survival, and mortality. It is useful for quickly comparing burden and prognosis across major sclerosing cholangitis subtypes.
Familial aggregation is supported by increased risk in first-degree relatives (reported as >10-fold increased in some summaries), consistent with polygenic inheritance. (okada2026distinctphenotypeof pages 5-7)
PSC diagnosis typically integrates: * Cholestatic liver tests (ALP/GGT predominant pattern) and * Cholangiographic findings on MRCP or ERCP showing multifocal strictures/beading, * With exclusion of secondary causes (including IgG4-SC, malignancy, stones). (ludwig2023secondarysclerosingcholangitis pages 1-3, giorgio2026primarysclerosingcholangitis pages 2-4)
MRCP is preferred as a first-line noninvasive test. (ludwig2023secondarysclerosingcholangitis pages 1-3)
The 2024 Japanese diagnostic criteria for PSC define large-duct PSC by strictures on cholangiography and small-duct PSC by normal cholangiography with PSC-consistent histology. Imaging criterion includes characteristic findings such as multifocal band-like strictures, beaded appearance, pruned-tree appearance, or diverticulum-like outpouching; laboratory criteria include elevated ALP (adults) or GGT (children) and histology may show onion-skin lesion/fibrous obliterative cholangitis. (naitoh2025the2024diagnostic pages 4-5)
Table summarizing these criteria is available as a cited figure/table capture. (naitoh2025the2024diagnostic media a72fe8f4)
The Mayo Risk Score is widely used in PSC and is incorporated into several trials and observational studies for risk stratification. (NCT02424175 chunk 1, giorgio2026primarysclerosingcholangitis pages 2-4)
Population-based and tertiary-cohort summaries cite median transplant-free survival ~14–21 years. (pitoni2025navigatingneoplasmrisk pages 1-2)
In COVID-19 SSC-CIP cohorts, prognosis is poor: incidence among invasively ventilated patients was ~1 in 43 with 1-year transplant-free survival ~40%. (leonhardt2023hepatobiliarylongtermconsequences pages 1-2)
In a tertiary-center COVID-19 SSC case series, mortality was 82% (14/17). (hofstetter2024endoscopiccharacterizationand pages 1-2)
A 2024 therapeutic review reports substantial ALP reduction in a fibrate trial (fenofibrate vs placebo) and ongoing bezafibrate and elafibranor programs. (fiorucci2024bileacidsbasedtherapies pages 16-18, fiorucci2024bileacidsbasedtherapies pages 11-12)
(ontology suggestions) * Liver transplantation (MAXO:0001175) * Endoscopic retrograde cholangiopancreatography (MAXO:0000587) * Balloon dilation of biliary stricture (procedure term; MAXO mapping may be institution-specific) * Biliary stenting (procedure term) * Colonoscopy surveillance (MAXO:0000507) * Antibiotic therapy (MAXO:0000127) * Fecal microbiota transplantation (MAXO:0000755)
Primary prevention strategies for PSC are not established due to unclear etiology. Current preventive care is largely secondary/tertiary prevention via surveillance and complication prevention: * Annual colonoscopy is widely recommended for PSC-IBD due to high CRC risk. (pitoni2025navigatingneoplasmrisk pages 1-2, pitoni2025navigatingneoplasmrisk pages 11-13) * Hepatobiliary malignancy surveillance commonly uses MRI/MRCP every 6–12 months ± CA19-9; gallbladder ultrasound surveillance every 6–12 months is discussed in cancer-risk reviews. (pitoni2025navigatingneoplasmrisk pages 11-13)
This tool run did not retrieve veterinary natural-history studies of sclerosing cholangitis across non-human species; therefore cross-species natural disease assertions cannot be made from the current evidence set.
1) PSC subtype-specific MONDO/Orphanet/OMIM identifiers were not retrieved in this tool run; only umbrella ontology mappings and MeSH were available. (OpenTargets Search: primary sclerosing cholangitis, NCT02943460 chunk 2) 2) ClinVar/gnomAD variant-level details (ACMG classes, allele frequencies) were not retrieved. 3) Some surveillance and guideline statements were available via reviews rather than primary guidelines; guideline PDFs (e.g., AASLD/EASL) were not directly retrieved in this run.
References
(ludwig2023secondarysclerosingcholangitis pages 1-3): Daniel R. Ludwig, Mark A. Anderson, Malak Itani, Kedar G. Sharbidre, Neeraj Lalwani, and Raj M. Paspulati. Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis. Abdominal Radiology (New York), 48:151-165, May 2023. URL: https://doi.org/10.1007/s00261-022-03551-z, doi:10.1007/s00261-022-03551-z. This article has 32 citations.
(moller2023secondarysclerosingcholangitis pages 1-2): Kathleen Möller, Barbara Braden, Emma L. Culver, Christian Jenssen, Ehsan Safai Zadeh, Amjad Alhyari, Christian Görg, André Ignee, Michael Hocke, Yi Dong, Siyu Sun, Siegbert Faiss, and Christoph F. Dietrich. Secondary sclerosing cholangitis and igg4-sclerosing cholangitis – a review of cholangiographic and ultrasound imaging. Endoscopic Ultrasound, 12:181-199, Dec 2023. URL: https://doi.org/10.4103/eus-d-22-00208, doi:10.4103/eus-d-22-00208. This article has 16 citations.
(crothers2024pastcurrentand pages 1-2): Hannah Crothers, James Ferguson, Mohammed Nabil Quraishi, Rachel Cooney, Tariq H. Iqbal, and Palak J. Trivedi. Past, current, and future trends in the prevalence of primary sclerosing cholangitis and inflammatory bowel disease across england (2015–2027): a nationwide, population-based study. The Lancet Regional Health - Europe, 44:101002, Sep 2024. URL: https://doi.org/10.1016/j.lanepe.2024.101002, doi:10.1016/j.lanepe.2024.101002. This article has 21 citations.
(pitoni2025navigatingneoplasmrisk pages 1-2): Demis Pitoni, Arianna Dal Buono, Roberto Gabbiadini, Vincenzo Ronca, Francesca Colapietro, Nicola Pugliese, Davide Giuseppe Ribaldone, Cristina Bezzio, Ana Lleo, and Alessandro Armuzzi. Navigating neoplasm risk in inflammatory bowel disease and primary sclerosing cholangitis. Cancers, 17:2165, Jun 2025. URL: https://doi.org/10.3390/cancers17132165, doi:10.3390/cancers17132165. This article has 1 citations.
(leibovitzh2024inflammatoryboweldisease pages 1-2): Haim Leibovitzh, Shadi Nayeri, Krzysztof Borowski, Cristian Hernandez-Rocha, Sun-Ho Lee, Williams Turpin, Joanne M Stempak, Iqbaljit Sandhu, Raquel Milgrom, Michelle I Smith, Kenneth Croitoru, Gideon M Hirschfield, Aliya Gulamhusein, and Mark S Silverberg. Inflammatory bowel disease associated with primary sclerosing cholangitis is associated with an altered gut microbiome and bile acid profile. Journal of Crohn's & Colitis, 18:1957-1966, Jul 2024. URL: https://doi.org/10.1093/ecco-jcc/jjae096, doi:10.1093/ecco-jcc/jjae096. This article has 22 citations.
(NCT03872921 chunk 1): norUrsodeoxycholic Acid vs Placebo in PSC. Dr. Falk Pharma GmbH. 2018. ClinicalTrials.gov Identifier: NCT03872921
(ludwig2023secondarysclerosingcholangitis pages 3-4): Daniel R. Ludwig, Mark A. Anderson, Malak Itani, Kedar G. Sharbidre, Neeraj Lalwani, and Raj M. Paspulati. Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis. Abdominal Radiology (New York), 48:151-165, May 2023. URL: https://doi.org/10.1007/s00261-022-03551-z, doi:10.1007/s00261-022-03551-z. This article has 32 citations.
(ludwig2023secondarysclerosingcholangitis pages 7-9): Daniel R. Ludwig, Mark A. Anderson, Malak Itani, Kedar G. Sharbidre, Neeraj Lalwani, and Raj M. Paspulati. Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis. Abdominal Radiology (New York), 48:151-165, May 2023. URL: https://doi.org/10.1007/s00261-022-03551-z, doi:10.1007/s00261-022-03551-z. This article has 32 citations.
(moller2023secondarysclerosingcholangitis pages 10-11): Kathleen Möller, Barbara Braden, Emma L. Culver, Christian Jenssen, Ehsan Safai Zadeh, Amjad Alhyari, Christian Görg, André Ignee, Michael Hocke, Yi Dong, Siyu Sun, Siegbert Faiss, and Christoph F. Dietrich. Secondary sclerosing cholangitis and igg4-sclerosing cholangitis – a review of cholangiographic and ultrasound imaging. Endoscopic Ultrasound, 12:181-199, Dec 2023. URL: https://doi.org/10.4103/eus-d-22-00208, doi:10.4103/eus-d-22-00208. This article has 16 citations.
(OpenTargets Search: primary sclerosing cholangitis): Open Targets Query (primary sclerosing cholangitis, 25 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(NCT02424175 chunk 2): Joshua Korzenik. Fecal Microbiota Transplantation for the Treatment of Primary Sclerosing Cholangitis.. Brigham and Women's Hospital. 2016. ClinicalTrials.gov Identifier: NCT02424175
(naitoh2025the2024diagnostic pages 4-5): Itaru Naitoh, Hiroyuki Isayama, Nobuhisa Akamatsu, Suguru Mizuno, Toshio Fujisawa, Nobuhiro Nakamoto, Yousuke Nakai, Shuichiro Umetsu, Mitsuyoshi Suzuki, Shintaro Yagi, Hironori Haga, Kenji Notohara, Katsuhiro Sano, Susumu Tazuma, Takahiro Nakazawa, and Atsushi Tanaka. The 2024 diagnostic criteria for primary sclerosing cholangitis. Journal of gastroenterology, Jun 2025. URL: https://doi.org/10.1007/s00535-025-02265-5, doi:10.1007/s00535-025-02265-5. This article has 12 citations and is from a domain leading peer-reviewed journal.
(giorgio2026primarysclerosingcholangitis pages 2-4): Sofia Svensson Di Giorgio, Chiara Maria Scandavini, Antonio Molinaro, Urban Arnelo, and Roberto Valente. Primary sclerosing cholangitis: diagnosis, management, and clinical challenges. Journal of Clinical Medicine, 15:1149, Feb 2026. URL: https://doi.org/10.3390/jcm15031149, doi:10.3390/jcm15031149. This article has 1 citations.
(naitoh2025the2024diagnostic media a72fe8f4): Itaru Naitoh, Hiroyuki Isayama, Nobuhisa Akamatsu, Suguru Mizuno, Toshio Fujisawa, Nobuhiro Nakamoto, Yousuke Nakai, Shuichiro Umetsu, Mitsuyoshi Suzuki, Shintaro Yagi, Hironori Haga, Kenji Notohara, Katsuhiro Sano, Susumu Tazuma, Takahiro Nakazawa, and Atsushi Tanaka. The 2024 diagnostic criteria for primary sclerosing cholangitis. Journal of gastroenterology, Jun 2025. URL: https://doi.org/10.1007/s00535-025-02265-5, doi:10.1007/s00535-025-02265-5. This article has 12 citations and is from a domain leading peer-reviewed journal.
(hofstetter2024endoscopiccharacterizationand pages 6-7): Pia Hofstetter, Ina Zuber-Jerger, Alexander Mehrl, Bernhard Graf, Dirk Lunz, Matthias Lubnow, Thomas Müller, Stephan Schmid, Martina Müller, and Arne Kandulski. Endoscopic characterization and outcome of covid-19 patients with secondary sclerosing cholangitis: a case series of a tertiary center. Journal of gastrointestinal and liver diseases : JGLD, 33 2:218-225, Jun 2024. URL: https://doi.org/10.15403/jgld-5476, doi:10.15403/jgld-5476. This article has 1 citations.
(leonhardt2023hepatobiliarylongtermconsequences pages 1-2): Silke Leonhardt, Christian Jürgensen, Josephine Frohme, Donata Grajecki, Andreas Adler, Michael Sigal, Julia Leonhardt, Julian M. Voll, Jan Matthias Kruse, Roland Körner, Kai-Uwe Eckardt, Hans-Joachim Janssen, Volker Gebhardt, Marc D. Schmittner, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, Elisa T. Helbig, Lena J. Lippert, Paula Stubbemann, Pinkus Tober-Lau, David Hillus, Sascha S. Haenel, Alexandra Horn, Willi M. Koch, Nadine Olk, Mirja Mittermaier, Fridolin Steinbeis, Tilman Lingscheid, Bettina Temmesfeld-Wollbrück, Thomas Zoller, Holger Müller-Redetzky, Alexander Uhrig, Daniel Grund, Christoph Ruwwe-Glösenkamp, Miriam S. Stegemann, Katrin M. Heim, Ralf H. Hübner, Christian Drosten, Victor M. Corman, Bastian Opitz, Martin Möckel, Felix Balzer, Claudia Spies, Steffen Weber-Carstens, Chantip Dang-Heine, Michael Hummel, Georg Schwanitz, Uwe D. Behrens, Maria Rönnefarth, Sein Schmidt, Alexander Krannich, Saskia Zvorc, Jenny Kollek, Christof von Kalle, Jan Doehn, Christoph Tabeling, Linda Jürgens, Malte Kleinschmidt, Sophy Denker, Moritz Pfeiffer, Belén Millet Pascual-Leone, Luisa Mrziglod, Felix Machleidt, Sebastian Albus, Felix Bremer, Tim Andermann, Carmen Garcia, Philipp Knape, Philipp M. Krause, Liron Lechtenberg, Yaosi Li, Panagiotis Pergantis, Till Jacobi, Teresa Ritter, Berna Yedikat, Lennart Pfannkuch, Christian Zobel, Ute Kellermann, Susanne Fieberg, Laure Bosquillon de Jarcy, Anne Wetzel, Markus C. Brack, Moritz Müller-Plathe, Daniel Zickler, Andreas Edel, Britta Stier, Nils B. Müller, Philipp Enghard, Lucie Kretzler, Lil A. Meyer-Arndt, Linna Li, Isabelle Wirsching, Denise Treue, Dana Briesemeister, Jenny Schlesinger, Daniel Wendisch, Anna L. Hiller, Sophie Brumhard, Christian Frey, Hendrik Müller-Ide, Michael Bauer, Charlotte Thibeault, Florian Kurth, Leif Erik Sander, Tobias Müller, and Frank Tacke. Hepatobiliary long-term consequences of covid-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill covid-19 patients. Hepatology International, 17:1610-1625, Apr 2023. URL: https://doi.org/10.1007/s12072-023-10521-0, doi:10.1007/s12072-023-10521-0. This article has 26 citations and is from a peer-reviewed journal.
(moller2023secondarysclerosingcholangitis pages 8-10): Kathleen Möller, Barbara Braden, Emma L. Culver, Christian Jenssen, Ehsan Safai Zadeh, Amjad Alhyari, Christian Görg, André Ignee, Michael Hocke, Yi Dong, Siyu Sun, Siegbert Faiss, and Christoph F. Dietrich. Secondary sclerosing cholangitis and igg4-sclerosing cholangitis – a review of cholangiographic and ultrasound imaging. Endoscopic Ultrasound, 12:181-199, Dec 2023. URL: https://doi.org/10.4103/eus-d-22-00208, doi:10.4103/eus-d-22-00208. This article has 16 citations.
(giorgio2026primarysclerosingcholangitis pages 7-9): Sofia Svensson Di Giorgio, Chiara Maria Scandavini, Antonio Molinaro, Urban Arnelo, and Roberto Valente. Primary sclerosing cholangitis: diagnosis, management, and clinical challenges. Journal of Clinical Medicine, 15:1149, Feb 2026. URL: https://doi.org/10.3390/jcm15031149, doi:10.3390/jcm15031149. This article has 1 citations.
(OpenTargets Search: primary sclerosing cholangitis,secondary sclerosing cholangitis): Open Targets Query (primary sclerosing cholangitis,secondary sclerosing cholangitis, 25 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(molodecky2011validityofadministrative pages 1-2): Natalie A. Molodecky, Robert P. Myers, Herman W. Barkema, Hude Quan, and Gilaad G. Kaplan. Validity of administrative data for the diagnosis of primary sclerosing cholangitis: a population‐based study. Liver International, 31:712-720, May 2011. URL: https://doi.org/10.1111/j.1478-3231.2011.02484.x, doi:10.1111/j.1478-3231.2011.02484.x. This article has 37 citations and is from a peer-reviewed journal.
(molodecky2011validityofadministrative pages 7-8): Natalie A. Molodecky, Robert P. Myers, Herman W. Barkema, Hude Quan, and Gilaad G. Kaplan. Validity of administrative data for the diagnosis of primary sclerosing cholangitis: a population‐based study. Liver International, 31:712-720, May 2011. URL: https://doi.org/10.1111/j.1478-3231.2011.02484.x, doi:10.1111/j.1478-3231.2011.02484.x. This article has 37 citations and is from a peer-reviewed journal.
(leung2025primarysclerosingcholangitis–inflammatory pages 1-2): Kristel K. Leung, Wenbin Li, Bettina Hansen, Aliya Gulamhusein, Lauren Lapointe-Shaw, Abdel Aziz Shaheen, Amanda Ricciuto, Eric I. Benchimol, Jennifer A. Flemming, and Gideon M. Hirschfield. Primary sclerosing cholangitis–inflammatory bowel disease: epidemiology, mortality, and impact of diagnostic sequence. JHEP Reports, 7:101272, Mar 2025. URL: https://doi.org/10.1016/j.jhepr.2024.101272, doi:10.1016/j.jhepr.2024.101272. This article has 16 citations and is from a peer-reviewed journal.
(hofstetter2024endoscopiccharacterizationand pages 1-2): Pia Hofstetter, Ina Zuber-Jerger, Alexander Mehrl, Bernhard Graf, Dirk Lunz, Matthias Lubnow, Thomas Müller, Stephan Schmid, Martina Müller, and Arne Kandulski. Endoscopic characterization and outcome of covid-19 patients with secondary sclerosing cholangitis: a case series of a tertiary center. Journal of gastrointestinal and liver diseases : JGLD, 33 2:218-225, Jun 2024. URL: https://doi.org/10.15403/jgld-5476, doi:10.15403/jgld-5476. This article has 1 citations.
(fiorucci2024bileacidsbasedtherapies pages 2-4): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(okada2026distinctphenotypeof pages 5-7): Haruka Okada, Shinya Sugimoto, Atsuto Kayashima, Yohei Mikami, Takanori Kanai, Nobuhiro Nakamoto, Yusuke Yoshimatsu, Hiroki Kiyohara, Yukie Nakadai, Ryosuke Kasuga, Nobuhito Taniki, Keisuke Ojiro, Shingo Usui, Shogo Sunaga, Ichiro Mizushima, Yuta Kaieda, Shohei Suzuki, Takaya Tabuchi, and Makoto Ueno. Distinct phenotype of primary sclerosing cholangitis-associated inflammatory bowel disease. Journal of Gastroenterology, Mar 2026. URL: https://doi.org/10.1007/s00535-026-02388-3, doi:10.1007/s00535-026-02388-3. This article has 0 citations and is from a domain leading peer-reviewed journal.
(pitoni2025navigatingneoplasmrisk pages 5-7): Demis Pitoni, Arianna Dal Buono, Roberto Gabbiadini, Vincenzo Ronca, Francesca Colapietro, Nicola Pugliese, Davide Giuseppe Ribaldone, Cristina Bezzio, Ana Lleo, and Alessandro Armuzzi. Navigating neoplasm risk in inflammatory bowel disease and primary sclerosing cholangitis. Cancers, 17:2165, Jun 2025. URL: https://doi.org/10.3390/cancers17132165, doi:10.3390/cancers17132165. This article has 1 citations.
(dong2024investigatingtheshared pages 1-3): Xuan Dong, Li-Li Gong, Mei-Zhu Hong, and Jin-Shui Pan. Investigating the shared genetic architecture between primary sclerosing cholangitis and inflammatory bowel diseases: a mendelian randomization study. BMC Gastroenterology, Feb 2024. URL: https://doi.org/10.1186/s12876-024-03162-6, doi:10.1186/s12876-024-03162-6. This article has 7 citations and is from a peer-reviewed journal.
(okada2026distinctphenotypeof pages 1-2): Haruka Okada, Shinya Sugimoto, Atsuto Kayashima, Yohei Mikami, Takanori Kanai, Nobuhiro Nakamoto, Yusuke Yoshimatsu, Hiroki Kiyohara, Yukie Nakadai, Ryosuke Kasuga, Nobuhito Taniki, Keisuke Ojiro, Shingo Usui, Shogo Sunaga, Ichiro Mizushima, Yuta Kaieda, Shohei Suzuki, Takaya Tabuchi, and Makoto Ueno. Distinct phenotype of primary sclerosing cholangitis-associated inflammatory bowel disease. Journal of Gastroenterology, Mar 2026. URL: https://doi.org/10.1007/s00535-026-02388-3, doi:10.1007/s00535-026-02388-3. This article has 0 citations and is from a domain leading peer-reviewed journal.
(bedke2024protectivefunctionof pages 1-2): Tanja Bedke, Friederike Stumme, Miriam Tomczak, Babett Steglich, Rongrong Jia, Simon Bohmann, Agnes Wittek, Jan Kempski, Emilia Göke, Marius Böttcher, Dominik Reher, Anissa Franke, Maximilian Lennartz, Till Clauditz, Guido Sauter, Thorben Fründt, Sören Weidemann, Gisa Tiegs, Christoph Schramm, Nicola Gagliani, Penelope Pelczar, and Samuel Huber. Protective function of sclerosing cholangitis on ibd. Gut, 73:1292-1301, Jun 2024. URL: https://doi.org/10.1136/gutjnl-2023-330856, doi:10.1136/gutjnl-2023-330856. This article has 38 citations and is from a highest quality peer-reviewed journal.
(bartoli2023secondarysclerosingcholangitis pages 1-2): Alessandra Bartoli, Carmela Cursaro, Hajrie Seferi, and Pietro Andreone. Secondary sclerosing cholangitis after sars-cov2: icu ketamine use or virus-specific biliary tropism and injury in the context of biliary ischemia in critically ill patients? Hepatic Medicine : Evidence and Research, 15:93-112, Aug 2023. URL: https://doi.org/10.2147/hmer.s384220, doi:10.2147/hmer.s384220. This article has 10 citations.
(leonhardt2023hepatobiliarylongtermconsequences pages 12-13): Silke Leonhardt, Christian Jürgensen, Josephine Frohme, Donata Grajecki, Andreas Adler, Michael Sigal, Julia Leonhardt, Julian M. Voll, Jan Matthias Kruse, Roland Körner, Kai-Uwe Eckardt, Hans-Joachim Janssen, Volker Gebhardt, Marc D. Schmittner, Stefan Hippenstiel, Martin Witzenrath, Norbert Suttorp, Elisa T. Helbig, Lena J. Lippert, Paula Stubbemann, Pinkus Tober-Lau, David Hillus, Sascha S. Haenel, Alexandra Horn, Willi M. Koch, Nadine Olk, Mirja Mittermaier, Fridolin Steinbeis, Tilman Lingscheid, Bettina Temmesfeld-Wollbrück, Thomas Zoller, Holger Müller-Redetzky, Alexander Uhrig, Daniel Grund, Christoph Ruwwe-Glösenkamp, Miriam S. Stegemann, Katrin M. Heim, Ralf H. Hübner, Christian Drosten, Victor M. Corman, Bastian Opitz, Martin Möckel, Felix Balzer, Claudia Spies, Steffen Weber-Carstens, Chantip Dang-Heine, Michael Hummel, Georg Schwanitz, Uwe D. Behrens, Maria Rönnefarth, Sein Schmidt, Alexander Krannich, Saskia Zvorc, Jenny Kollek, Christof von Kalle, Jan Doehn, Christoph Tabeling, Linda Jürgens, Malte Kleinschmidt, Sophy Denker, Moritz Pfeiffer, Belén Millet Pascual-Leone, Luisa Mrziglod, Felix Machleidt, Sebastian Albus, Felix Bremer, Tim Andermann, Carmen Garcia, Philipp Knape, Philipp M. Krause, Liron Lechtenberg, Yaosi Li, Panagiotis Pergantis, Till Jacobi, Teresa Ritter, Berna Yedikat, Lennart Pfannkuch, Christian Zobel, Ute Kellermann, Susanne Fieberg, Laure Bosquillon de Jarcy, Anne Wetzel, Markus C. Brack, Moritz Müller-Plathe, Daniel Zickler, Andreas Edel, Britta Stier, Nils B. Müller, Philipp Enghard, Lucie Kretzler, Lil A. Meyer-Arndt, Linna Li, Isabelle Wirsching, Denise Treue, Dana Briesemeister, Jenny Schlesinger, Daniel Wendisch, Anna L. Hiller, Sophie Brumhard, Christian Frey, Hendrik Müller-Ide, Michael Bauer, Charlotte Thibeault, Florian Kurth, Leif Erik Sander, Tobias Müller, and Frank Tacke. Hepatobiliary long-term consequences of covid-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill covid-19 patients. Hepatology International, 17:1610-1625, Apr 2023. URL: https://doi.org/10.1007/s12072-023-10521-0, doi:10.1007/s12072-023-10521-0. This article has 26 citations and is from a peer-reviewed journal.
(fousekis2025gut–liveraxismicrobiota pages 2-4): Fotios S. Fousekis, Konstantinos Mpakogiannis, Georgios D. Lianos, Elisabetta Antonelli, Gabrio Bassotti, and Konstantinos H. Katsanos. Gut–liver axis, microbiota, bile acids, and immune response in pathogenesis of primary sclerosing cholangitis: an overview. Journal of Clinical Medicine, 14:7817, Nov 2025. URL: https://doi.org/10.3390/jcm14217817, doi:10.3390/jcm14217817. This article has 6 citations.
(fousekis2025gut–liveraxismicrobiota pages 10-11): Fotios S. Fousekis, Konstantinos Mpakogiannis, Georgios D. Lianos, Elisabetta Antonelli, Gabrio Bassotti, and Konstantinos H. Katsanos. Gut–liver axis, microbiota, bile acids, and immune response in pathogenesis of primary sclerosing cholangitis: an overview. Journal of Clinical Medicine, 14:7817, Nov 2025. URL: https://doi.org/10.3390/jcm14217817, doi:10.3390/jcm14217817. This article has 6 citations.
(fiorucci2024bileacidsbasedtherapies pages 9-10): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(fousekis2025gut–liveraxismicrobiota pages 7-9): Fotios S. Fousekis, Konstantinos Mpakogiannis, Georgios D. Lianos, Elisabetta Antonelli, Gabrio Bassotti, and Konstantinos H. Katsanos. Gut–liver axis, microbiota, bile acids, and immune response in pathogenesis of primary sclerosing cholangitis: an overview. Journal of Clinical Medicine, 14:7817, Nov 2025. URL: https://doi.org/10.3390/jcm14217817, doi:10.3390/jcm14217817. This article has 6 citations.
(bartoli2023secondarysclerosingcholangitis pages 7-8): Alessandra Bartoli, Carmela Cursaro, Hajrie Seferi, and Pietro Andreone. Secondary sclerosing cholangitis after sars-cov2: icu ketamine use or virus-specific biliary tropism and injury in the context of biliary ischemia in critically ill patients? Hepatic Medicine : Evidence and Research, 15:93-112, Aug 2023. URL: https://doi.org/10.2147/hmer.s384220, doi:10.2147/hmer.s384220. This article has 10 citations.
(NCT02424175 chunk 1): Joshua Korzenik. Fecal Microbiota Transplantation for the Treatment of Primary Sclerosing Cholangitis.. Brigham and Women's Hospital. 2016. ClinicalTrials.gov Identifier: NCT02424175
(fiorucci2024bileacidsbasedtherapies pages 10-11): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(NCT02943460 chunk 1): Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis. Gilead Sciences. 2016. ClinicalTrials.gov Identifier: NCT02943460
(fiorucci2024bileacidsbasedtherapies pages 12-13): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(fiorucci2024bileacidsbasedtherapies pages 13-15): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(NCT03710122 chunk 1): Elizabeth Carey. Vancomycin for Primary Sclerosing Cholangitis. Elizabeth Carey. 2020. ClinicalTrials.gov Identifier: NCT03710122
(NCT05876182 chunk 1): Vancomycin in Primary Sclerosing Cholangitis in Italy. University of Milano Bicocca. 2023. ClinicalTrials.gov Identifier: NCT05876182
(fiorucci2024bileacidsbasedtherapies pages 16-18): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(fiorucci2024bileacidsbasedtherapies pages 11-12): Stefano Fiorucci, Ginevra Urbani, Cristina Di Giorgio, Michele Biagioli, and Eleonora Distrutti. Bile acids-based therapies for primary sclerosing cholangitis: current landscape and future developments. Cells, 13:1650, Oct 2024. URL: https://doi.org/10.3390/cells13191650, doi:10.3390/cells13191650. This article has 16 citations.
(pitoni2025navigatingneoplasmrisk pages 11-13): Demis Pitoni, Arianna Dal Buono, Roberto Gabbiadini, Vincenzo Ronca, Francesca Colapietro, Nicola Pugliese, Davide Giuseppe Ribaldone, Cristina Bezzio, Ana Lleo, and Alessandro Armuzzi. Navigating neoplasm risk in inflammatory bowel disease and primary sclerosing cholangitis. Cancers, 17:2165, Jun 2025. URL: https://doi.org/10.3390/cancers17132165, doi:10.3390/cancers17132165. This article has 1 citations.
(NCT02943460 chunk 2): Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis. Gilead Sciences. 2016. ClinicalTrials.gov Identifier: NCT02943460