👪

Inheritance

1

Autosomal recessive inheritance HP:0000007

VODI results from biallelic SP110 pathogenic variants inherited in an autosomal recessive pattern.

Autosomal recessive inheritance

Show evidence (1 reference)

PMID:17510920 SUPPORT Human Clinical

"Homozygous mutations in the gene SP110 are the genetic basis of VODI."

This directly supports autosomal recessive inheritance of VODI.

⚙

Pathophysiology

7

SP110 loss of function

VODI is caused by pathogenic loss of SP110, a PML nuclear body-associated protein, establishing the initiating molecular lesion of the syndrome.

SP110 link

Downstream

Defective adaptive immune maturation SP110 deficiency disrupts immune development and humoral differentiation.

Hepatic sinusoidal and terminal venular occlusion SP110 deficiency is linked to the hepatic vascular injury arm of the syndrome.

Show evidence (1 reference)

PMID:16648851 SUPPORT Human Clinical

"We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno-occlusive disease with immunodeficiency"

This landmark discovery paper directly supports SP110 deficiency as the initiating cause of VODI.

Defective adaptive immune maturation

SP110 deficiency impairs humoral and cellular immune maturation, with absent germinal centers and plasma cells despite circulating lymphocyte numbers that may be preserved.

T cell link B cell link

B cell differentiation link adaptive immune response link

Downstream

Combined immunodeficiency with impaired pathogen control Defective immune maturation produces recurrent bacterial and opportunistic infections.

Show evidence (1 reference)

PMID:16648851 SUPPORT Human Clinical

"an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells"

This directly supports a core immune-maturation defect affecting both humoral and cellular immunity in VODI.

Combined immunodeficiency with impaired pathogen control

The immune defect in VODI leads to early severe infection susceptibility, including Pneumocystis and candidiasis, alongside profound antibody deficiency.

immune response link

Downstream

Opportunistic pulmonary infection susceptibility Combined immunodeficiency predisposes to Pneumocystis and other opportunistic infections.

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"Bacterial and opportunistic infections including Pneumocystis jirovecii infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections occur."

This supports impaired pathogen control as a major downstream consequence of the combined immunodeficiency in VODI.

Opportunistic pulmonary infection susceptibility

Profound combined immunodeficiency in VODI predisposes infants to severe opportunistic pulmonary infections, particularly Pneumocystis jirovecii pneumonia.

immune response link

lung link

Downstream

Pneumocystis jirovecii pneumonia Opportunistic immune failure can culminate in Pneumocystis jirovecii pneumonia.

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"Bacterial and opportunistic infections including Pneumocystis jirovecii infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections occur."

This supports a discrete downstream susceptibility node for opportunistic pulmonary infection in VODI.

Hepatic sinusoidal and terminal venular occlusion

Hepatic disease in VODI is characterized by lobular vascular occlusion and sinusoidal/terminal venular injury that progresses to fibrosis and hepatic failure.

liver link

Downstream

Hepatic stellate cell activation and fibrotic remodeling Ongoing vascular and parenchymal injury promotes fibrotic liver remodeling.

Show evidence (2 references)

PMID:20301448 SUPPORT Other

"terminal hepatic lobular vascular occlusion and hepatic fibrosis manifesting as hepatomegaly and/or hepatic failure"

This directly supports hepatic vascular occlusion as the key liver lesion in VODI.

PMID:25755580 PARTIAL Other

"A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules."

This broader SOS review supports the downstream endothelial-injury and terminal venule-occlusion mechanism relevant to the hepatic arm of VODI.

Hepatic stellate cell activation and fibrotic remodeling

Persistent hepatic vascular injury drives mesenchymal activation and liver-specific fibrotic remodeling, consistent with the shared fibrotic response module.

hepatic stellate cell link

liver link

Downstream

Progressive hepatic fibrosis and organ dysfunction Activated hepatic mesenchymal cells contribute to irreversible fibrotic liver injury.

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"terminal hepatic lobular vascular occlusion and hepatic fibrosis manifesting as hepatomegaly and/or hepatic failure"

This supports a downstream liver-fibrosis branch in VODI after the vascular occlusion lesion is established.

Progressive hepatic fibrosis and organ dysfunction

Progressive hepatic fibrosis drives hepatomegaly, ascites, and hepatic failure in advanced VODI.

liver link

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"terminal hepatic lobular vascular occlusion and hepatic fibrosis manifesting as hepatomegaly and/or hepatic failure"

This directly supports progressive fibrotic liver dysfunction as a major downstream outcome of VODI.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

6

Blood 1

Hypogammaglobulinemia Decreased circulating immunoglobulin concentration (HP:0004313)

Show evidence (1 reference)

PMID:16648851 SUPPORT Human Clinical

"an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency"

This directly supports severe hypogammaglobulinemia as a core phenotype in VODI.

Digestive 3

Hepatomegaly Hepatomegaly (HP:0002240)

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"terminal hepatic lobular vascular occlusion and hepatic fibrosis manifesting as hepatomegaly and/or hepatic failure"

This directly supports hepatomegaly as a characteristic hepatic phenotype of VODI.

Acute hepatic failure Acute hepatic failure (HP:0006554)

Show evidence (1 reference)

PMID:17510920 SUPPORT Human Clinical

"The proband in this report presented at three months of age with hepatomegaly hepatic failure and was found to have hypogammaglobulinemia."

This directly supports early hepatic failure as a clinically important manifestation of VODI.

Ascites Ascites (HP:0001541)

Show evidence (1 reference)

PMID:25755580 PARTIAL Other

"The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain."

This broader SOS evidence supports ascites as a plausible downstream phenotype of the hepatic veno-occlusive process in VODI.

Immune 2

Combined immunodeficiency Combined immunodeficiency (HP:0005387)

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"Hepatic veno-occlusive disease with immunodeficiency (VODI) is characterized by (1) combined immunodeficiency"

This directly supports combined immunodeficiency as a defining phenotype of VODI.

Pneumocystis jirovecii pneumonia Pneumocystis jirovecii pneumonia (HP:0020102)

Show evidence (1 reference)

PMID:22982295 SUPPORT Human Clinical

"broncho-alveolar lavage detected Pneumocystis jiroveci."

This directly supports Pneumocystis infection as an opportunistic infectious phenotype in VODI.

🧬

Genetic Associations

1

SP110 (Causal biallelic pathogenic variants)

Show evidence (2 references)

PMID:20301448 SUPPORT Other

"DIAGNOSIS/TESTING: The diagnosis of VODI is established in a proband who meets clinical diagnostic criteria or by identification of biallelic pathogenic variants in SP110 on molecular genetic testing."

This directly supports SP110 as the causal gene and molecular basis of VODI.

CGGV:assertion_ee8bf8d3-46b2-4b29-b729-734c952ada99-2023-10-19T160000.000Z SUPPORT Other

ClinGen classifies the SP110-hepatic veno-occlusive disease-immunodeficiency syndrome gene-disease relationship as definitive with autosomal recessive inheritance.

💊

Treatments

5

Immunoglobulin replacement therapy

Action: immunoglobulin replacement therapy Ontology label: pharmacotherapy MAXO:0000058

Intravenous or subcutaneous immunoglobulin replacement improves survival and infection control in affected infants.

Target Phenotypes: Hypogammaglobulinemia ↗

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"In the past the prognosis for affected individuals was poor, with 100% mortality in the first year of life if unrecognized and untreated with intravenous or subcutaneous immunoglobulin (IVIG/SCIG)"

This directly supports immunoglobulin replacement as a core life-saving therapy in VODI.

Defibrotide

Action: defibrotide therapy Ontology label: pharmacotherapy MAXO:0000058

Defibrotide is used for acute hepatic disease and prophylactically around HSCT in VODI.

Target Phenotypes: Acute hepatic failure ↗

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"MANAGEMENT: Targeted therapies: IVIG/SCIG; defibrotide for acute hepatic disease; HSCT with non-hepatotoxic conditioning therapy, preferably with defibrotide prophylaxis."

This directly supports defibrotide as a disease-relevant hepatic therapy in VODI.

Hematopoietic stem cell transplantation

Action: hematopoietic stem cell transplantation MAXO:0000747

Early HSCT with non-hepatotoxic conditioning is a potentially curative treatment strategy for VODI.

Target Phenotypes: Combined immunodeficiency ↗

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"Early hematopoietic stem cell transplantation (HSCT) using non-hepatoxic drugs in conditioning and prophylactic defibrotide is potentially curative."

This directly supports HSCT as a potentially curative therapy for VODI.

Pneumocystis jirovecii prophylaxis

Action: pharmacotherapy MAXO:0000058

Prophylaxis against Pneumocystis jirovecii is part of standard supportive care for affected infants with profound combined immunodeficiency.

Target Phenotypes: Pneumocystis jirovecii pneumonia ↗

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"Supportive care: Pneumocystis jirovecii prophylaxis; prompt treatment of infections with antibacterials, antivirals, or antifungals as indicated;"

This directly supports Pneumocystis prophylaxis as routine supportive management in VODI.

Liver transplantation

Action: organ transplantation MAXO:0010039

Liver transplantation may be considered in severe hepatic failure, although complications can be substantial in this immunodeficient syndrome.

Target Phenotypes: Acute hepatic failure ↗

Show evidence (1 reference)

PMID:20301448 SUPPORT Other

"consider liver transplantation, although rate of complications may be high."

This supports liver transplantation as a rescue option for severe hepatic disease in VODI.

🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Hepatic veno-occlusive disease-immunodeficiency syndrome:

Severe combined immunodeficiency Not Yet Curated MONDO:0015974

Overlapping Features VODI can initially resemble severe combined immunodeficiency because of early opportunistic infections and profound immune dysfunction.

Distinguishing Features

Hepatic veno-occlusive disease and hepatic fibrosis favor VODI.
Biallelic SP110 variants support VODI, and TREC-based newborn SCID screening may miss it.

Show evidence (1 reference)

PMID:22982295 SUPPORT Human Clinical

"Familial hepatic veno-occlusive disease with immunodeficiency (VODI, OMIM: 235550), a rare form of severe combined immune deficiency"

This directly supports severe combined immunodeficiency as an important overlapping diagnosis that VODI may mimic.

Hepatic veno-occlusive disease Not Yet Curated MONDO:0019514

Overlapping Features Isolated hepatic veno-occlusive disease or sinusoidal obstruction syndrome overlaps with the liver phenotype of VODI but lacks the syndromic immune defect.

Distinguishing Features

Severe hypogammaglobulinemia and combined immunodeficiency favor VODI.
Identification of biallelic SP110 variants distinguishes the inherited syndromic form.

Show evidence (1 reference)

PMID:16648851 SUPPORT Human Clinical

"severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease"

This supports distinguishing the inherited immunodeficiency syndrome from isolated hepatic veno-occlusive disease.

{ }

Source YAML

click to show

name: Hepatic veno-occlusive disease-immunodeficiency syndrome
creation_date: "2026-04-21T14:07:20Z"
updated_date: "2026-04-21T23:55:00Z"
category: Mendelian
parents:
- hereditary disease
- primary immunodeficiency
synonyms:
- VODI
- VODI syndrome
- hepatic veno-occlusive disease with immunodeficiency
description: >-
  Hepatic veno-occlusive disease-immunodeficiency syndrome is a rare autosomal
  recessive SP110-related primary immunodeficiency characterized by severe
  hypogammaglobulinemia, combined immunodeficiency, absent germinal centers and
  plasma cells, and early-onset hepatic sinusoidal/terminal venular occlusion
  with progressive hepatic fibrosis. Available evidence supports a causal chain
  from SP110 deficiency to defective adaptive immune maturation with
  opportunistic infection susceptibility and a parallel hepatic vascular-fibrotic
  injury program.
disease_term:
  preferred_term: hepatic veno-occlusive disease-immunodeficiency syndrome
  term:
    id: MONDO:0009338
    label: hepatic veno-occlusive disease-immunodeficiency syndrome
inheritance:
- name: Autosomal recessive inheritance
  description: >-
    VODI results from biallelic SP110 pathogenic variants inherited in an
    autosomal recessive pattern.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:17510920
    reference_title: "The first prenatal diagnosis for veno-occlusive disease and immunodeficiency syndrome, an autosomal recessive condition associated with mutations in SP110."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Homozygous mutations in the gene SP110 are the genetic basis of VODI.
    explanation: >-
      This directly supports autosomal recessive inheritance of VODI.
pathophysiology:
- name: SP110 loss of function
  description: >-
    VODI is caused by pathogenic loss of SP110, a PML nuclear body-associated
    protein, establishing the initiating molecular lesion of the syndrome.
  genes:
  - preferred_term: SP110
    term:
      id: hgnc:5401
      label: SP110
  evidence:
  - reference: PMID:16648851
    reference_title: Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We describe mutations in the PML nuclear body protein Sp110 in the
      syndrome veno-occlusive disease with immunodeficiency
    explanation: >-
      This landmark discovery paper directly supports SP110 deficiency as the
      initiating cause of VODI.
  downstream:
  - target: Defective adaptive immune maturation
    description: SP110 deficiency disrupts immune development and humoral differentiation.
  - target: Hepatic sinusoidal and terminal venular occlusion
    description: SP110 deficiency is linked to the hepatic vascular injury arm of the syndrome.
- name: Defective adaptive immune maturation
  description: >-
    SP110 deficiency impairs humoral and cellular immune maturation, with absent
    germinal centers and plasma cells despite circulating lymphocyte numbers
    that may be preserved.
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  biological_processes:
  - preferred_term: B cell differentiation
    term:
      id: GO:0030183
      label: B cell differentiation
  - preferred_term: adaptive immune response
    term:
      id: GO:0002250
      label: adaptive immune response
  evidence:
  - reference: PMID:16648851
    reference_title: Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      an autosomal recessive disorder of severe hypogammaglobulinemia, combined
      T and B cell immunodeficiency, absent lymph node germinal centers, absent
      tissue plasma cells
    explanation: >-
      This directly supports a core immune-maturation defect affecting both
      humoral and cellular immunity in VODI.
  downstream:
  - target: Combined immunodeficiency with impaired pathogen control
    description: Defective immune maturation produces recurrent bacterial and opportunistic infections.
- name: Combined immunodeficiency with impaired pathogen control
  description: >-
    The immune defect in VODI leads to early severe infection susceptibility,
    including Pneumocystis and candidiasis, alongside profound antibody
    deficiency.
  biological_processes:
  - preferred_term: immune response
    term:
      id: GO:0006955
      label: immune response
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bacterial and opportunistic infections including Pneumocystis jirovecii
      infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus
      infections occur.
    explanation: >-
      This supports impaired pathogen control as a major downstream consequence
      of the combined immunodeficiency in VODI.
  downstream:
  - target: Opportunistic pulmonary infection susceptibility
    description: Combined immunodeficiency predisposes to Pneumocystis and other opportunistic infections.
- name: Opportunistic pulmonary infection susceptibility
  description: >-
    Profound combined immunodeficiency in VODI predisposes infants to severe
    opportunistic pulmonary infections, particularly Pneumocystis jirovecii
    pneumonia.
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  biological_processes:
  - preferred_term: immune response
    term:
      id: GO:0006955
      label: immune response
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Bacterial and opportunistic infections including Pneumocystis jirovecii
      infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus
      infections occur.
    explanation: >-
      This supports a discrete downstream susceptibility node for opportunistic
      pulmonary infection in VODI.
  downstream:
  - target: Pneumocystis jirovecii pneumonia
    description: Opportunistic immune failure can culminate in Pneumocystis jirovecii pneumonia.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22982295
      reference_title: "Hepatic veno-occlusive disease with immunodeficiency (VODI): first reported case in the U.S. and identification of a unique mutation in Sp110."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        broncho-alveolar lavage detected Pneumocystis jiroveci.
      explanation: >-
        This directly links opportunistic pulmonary infection susceptibility to
        the observed Pneumocystis pneumonia phenotype in VODI.
- name: Hepatic sinusoidal and terminal venular occlusion
  description: >-
    Hepatic disease in VODI is characterized by lobular vascular occlusion and
    sinusoidal/terminal venular injury that progresses to fibrosis and hepatic
    failure.
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      terminal hepatic lobular vascular occlusion and hepatic fibrosis
      manifesting as hepatomegaly and/or hepatic failure
    explanation: >-
      This directly supports hepatic vascular occlusion as the key liver lesion
      in VODI.
  - reference: PMID:25755580
    reference_title: Sinusoidal obstruction syndrome (hepatic veno-occlusive disease).
    supports: PARTIAL
    evidence_source: OTHER
    snippet: >-
      A central pathogenic event is toxic destruction of hepatic sinusoidal
      endothelial cells (SEC), with sloughing and downstream occlusion of
      terminal hepatic venules.
    explanation: >-
      This broader SOS review supports the downstream endothelial-injury and
      terminal venule-occlusion mechanism relevant to the hepatic arm of VODI.
  downstream:
  - target: Hepatic stellate cell activation and fibrotic remodeling
    description: Ongoing vascular and parenchymal injury promotes fibrotic liver remodeling.
- name: Hepatic stellate cell activation and fibrotic remodeling
  conforms_to: "fibrotic_response#Mesenchymal Cell Activation"
  description: >-
    Persistent hepatic vascular injury drives mesenchymal activation and
    liver-specific fibrotic remodeling, consistent with the shared fibrotic
    response module.
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  cell_types:
  - preferred_term: hepatic stellate cell
    term:
      id: CL:0000632
      label: hepatic stellate cell
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      terminal hepatic lobular vascular occlusion and hepatic fibrosis
      manifesting as hepatomegaly and/or hepatic failure
    explanation: >-
      This supports a downstream liver-fibrosis branch in VODI after the
      vascular occlusion lesion is established.
  downstream:
  - target: Progressive hepatic fibrosis and organ dysfunction
    description: Activated hepatic mesenchymal cells contribute to irreversible fibrotic liver injury.
- name: Progressive hepatic fibrosis and organ dysfunction
  conforms_to: "fibrotic_response#Excessive ECM Deposition"
  description: >-
    Progressive hepatic fibrosis drives hepatomegaly, ascites, and hepatic
    failure in advanced VODI.
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      terminal hepatic lobular vascular occlusion and hepatic fibrosis
      manifesting as hepatomegaly and/or hepatic failure
    explanation: >-
      This directly supports progressive fibrotic liver dysfunction as a major
      downstream outcome of VODI.
phenotypes:
- name: Combined immunodeficiency
  category: Immunologic
  diagnostic: true
  description: Combined immunodeficiency is a defining immunologic feature of VODI.
  phenotype_term:
    preferred_term: Combined immunodeficiency
    term:
      id: HP:0005387
      label: Combined immunodeficiency
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Hepatic veno-occlusive disease with immunodeficiency (VODI) is
      characterized by (1) combined immunodeficiency
    explanation: >-
      This directly supports combined immunodeficiency as a defining phenotype
      of VODI.
- name: Hypogammaglobulinemia
  category: Immunologic
  diagnostic: true
  description: Severe hypogammaglobulinemia is a central laboratory and clinical feature of the syndrome.
  phenotype_term:
    preferred_term: Hypogammaglobulinemia
    term:
      id: HP:0004313
      label: Decreased circulating immunoglobulin concentration
  evidence:
  - reference: PMID:16648851
    reference_title: Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      an autosomal recessive disorder of severe hypogammaglobulinemia, combined
      T and B cell immunodeficiency
    explanation: >-
      This directly supports severe hypogammaglobulinemia as a core phenotype in
      VODI.
- name: Hepatomegaly
  category: Gastrointestinal
  diagnostic: true
  description: Hepatomegaly is a common early hepatic manifestation of VODI.
  phenotype_term:
    preferred_term: Hepatomegaly
    term:
      id: HP:0002240
      label: Hepatomegaly
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      terminal hepatic lobular vascular occlusion and hepatic fibrosis
      manifesting as hepatomegaly and/or hepatic failure
    explanation: >-
      This directly supports hepatomegaly as a characteristic hepatic phenotype
      of VODI.
- name: Acute hepatic failure
  category: Gastrointestinal
  description: Progressive hepatic vascular-fibrotic injury can culminate in hepatic failure during infancy.
  phenotype_term:
    preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  evidence:
  - reference: PMID:17510920
    reference_title: "The first prenatal diagnosis for veno-occlusive disease and immunodeficiency syndrome, an autosomal recessive condition associated with mutations in SP110."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The proband in this report presented at three months of age with
      hepatomegaly hepatic failure and was found to have
      hypogammaglobulinemia.
    explanation: >-
      This directly supports early hepatic failure as a clinically important
      manifestation of VODI.
- name: Ascites
  category: Gastrointestinal
  description: Ascites can develop as part of advanced hepatic sinusoidal obstruction and liver dysfunction.
  phenotype_term:
    preferred_term: Ascites
    term:
      id: HP:0001541
      label: Ascites
  evidence:
  - reference: PMID:25755580
    reference_title: Sinusoidal obstruction syndrome (hepatic veno-occlusive disease).
    supports: PARTIAL
    evidence_source: OTHER
    snippet: >-
      The clinical presentation of SOS includes jaundice, development of right
      upper-quadrant pain and tender hepatomegaly, ascites, and unexplained
      weight gain.
    explanation: >-
      This broader SOS evidence supports ascites as a plausible downstream
      phenotype of the hepatic veno-occlusive process in VODI.
- name: Pneumocystis jirovecii pneumonia
  category: Infectious
  description: Opportunistic Pneumocystis infection reflects the syndrome's combined immunodeficiency.
  phenotype_term:
    preferred_term: Pneumocystis jirovecii pneumonia
    term:
      id: HP:0020102
      label: Pneumocystis jirovecii pneumonia
  evidence:
  - reference: PMID:22982295
    reference_title: "Hepatic veno-occlusive disease with immunodeficiency (VODI): first reported case in the U.S. and identification of a unique mutation in Sp110."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      broncho-alveolar lavage detected Pneumocystis jiroveci.
    explanation: >-
      This directly supports Pneumocystis infection as an opportunistic
      infectious phenotype in VODI.
biochemical: []
genetic:
- name: SP110
  association: Causal biallelic pathogenic variants
  gene_term:
    preferred_term: SP110
    term:
      id: hgnc:5401
      label: SP110
  notes: >-
    VODI is established by identifying biallelic pathogenic variants in SP110,
    including truncating and missense variants associated with profound immune
    and hepatic disease.
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      DIAGNOSIS/TESTING: The diagnosis of VODI is established in a proband who
      meets clinical diagnostic criteria or by identification of biallelic
      pathogenic variants in SP110 on molecular genetic testing.
    explanation: >-
      This directly supports SP110 as the causal gene and molecular basis of
      VODI.
  - reference: CGGV:assertion_ee8bf8d3-46b2-4b29-b729-734c952ada99-2023-10-19T160000.000Z
    reference_title: "SP110 / hepatic veno-occlusive disease-immunodeficiency syndrome (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SP110 | HGNC:5401 | hepatic veno-occlusive disease-immunodeficiency syndrome | MONDO:0009338 | AR | Definitive"
    explanation: ClinGen classifies the SP110-hepatic veno-occlusive disease-immunodeficiency syndrome gene-disease relationship as definitive with autosomal recessive inheritance.
environmental: []
treatments:
- name: Immunoglobulin replacement therapy
  description: >-
    Intravenous or subcutaneous immunoglobulin replacement improves survival and
    infection control in affected infants.
  treatment_term:
    preferred_term: immunoglobulin replacement therapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  target_phenotypes:
  - preferred_term: Hypogammaglobulinemia
    term:
      id: HP:0004313
      label: Decreased circulating immunoglobulin concentration
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In the past the prognosis for affected individuals was poor, with 100%
      mortality in the first year of life if unrecognized and untreated with
      intravenous or subcutaneous immunoglobulin (IVIG/SCIG)
    explanation: >-
      This directly supports immunoglobulin replacement as a core life-saving
      therapy in VODI.
- name: Defibrotide
  description: Defibrotide is used for acute hepatic disease and prophylactically around HSCT in VODI.
  treatment_term:
    preferred_term: defibrotide therapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  target_phenotypes:
  - preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MANAGEMENT: Targeted therapies: IVIG/SCIG; defibrotide for acute hepatic
      disease; HSCT with non-hepatotoxic conditioning therapy, preferably with
      defibrotide prophylaxis.
    explanation: >-
      This directly supports defibrotide as a disease-relevant hepatic therapy
      in VODI.
- name: Hematopoietic stem cell transplantation
  description: >-
    Early HSCT with non-hepatotoxic conditioning is a potentially curative
    treatment strategy for VODI.
  treatment_term:
    preferred_term: hematopoietic stem cell transplantation
    term:
      id: MAXO:0000747
      label: hematopoietic stem cell transplantation
  target_phenotypes:
  - preferred_term: Combined immunodeficiency
    term:
      id: HP:0005387
      label: Combined immunodeficiency
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Early hematopoietic stem cell transplantation (HSCT) using
      non-hepatoxic drugs in conditioning and prophylactic defibrotide is
      potentially curative.
    explanation: >-
      This directly supports HSCT as a potentially curative therapy for VODI.
- name: Pneumocystis jirovecii prophylaxis
  description: >-
    Prophylaxis against Pneumocystis jirovecii is part of standard supportive
    care for affected infants with profound combined immunodeficiency.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  target_phenotypes:
  - preferred_term: Pneumocystis jirovecii pneumonia
    term:
      id: HP:0020102
      label: Pneumocystis jirovecii pneumonia
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Supportive care: Pneumocystis jirovecii prophylaxis; prompt treatment of
      infections with antibacterials, antivirals, or antifungals as indicated;
    explanation: >-
      This directly supports Pneumocystis prophylaxis as routine supportive
      management in VODI.
- name: Liver transplantation
  description: >-
    Liver transplantation may be considered in severe hepatic failure, although
    complications can be substantial in this immunodeficient syndrome.
  treatment_term:
    preferred_term: organ transplantation
    term:
      id: MAXO:0010039
      label: organ transplantation
  target_phenotypes:
  - preferred_term: Acute hepatic failure
    term:
      id: HP:0006554
      label: Acute hepatic failure
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      consider liver transplantation, although rate of complications may be
      high.
    explanation: >-
      This supports liver transplantation as a rescue option for severe hepatic
      disease in VODI.
diagnosis:
- name: SP110 molecular genetic testing
  description: >-
    Molecular confirmation relies on identifying biallelic pathogenic SP110
    variants in a patient with compatible immune and hepatic findings.
  results: Biallelic pathogenic SP110 variants establish the diagnosis of VODI.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
    qualifiers:
    - predicate:
        preferred_term: has participant
        term:
          id: RO:0000057
          label: has participant
      value:
        preferred_term: SP110
        term:
          id: hgnc:5401
          label: SP110
  evidence:
  - reference: PMID:20301448
    reference_title: Hepatic Veno-Occlusive Disease with Immunodeficiency.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The diagnosis of VODI is established in a proband who meets clinical
      diagnostic criteria or by identification of biallelic pathogenic variants
      in SP110 on molecular genetic testing.
    explanation: >-
      This directly supports SP110-focused molecular testing as the key
      confirmatory diagnostic procedure for VODI.
- name: Liver biopsy
  description: >-
    Liver biopsy can document the sinusoidal obstruction or veno-occlusive
    lesion when hepatic disease is present.
  results: Histology consistent with hepatic veno-occlusive disease supports the diagnosis.
  diagnosis_term:
    preferred_term: biopsy of liver
    term:
      id: MAXO:0000376
      label: biopsy of liver
  evidence:
  - reference: PMID:22982295
    reference_title: "Hepatic veno-occlusive disease with immunodeficiency (VODI): first reported case in the U.S. and identification of a unique mutation in Sp110."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Liver biopsies at ages 5 and 9 months were consistent with hepatic
      veno-occlusive disease or hVOD (also known as sinusoidal obstruction
      syndrome or SOS)
    explanation: >-
      This directly supports liver biopsy as a diagnostic procedure documenting
      the characteristic hepatic lesion in VODI.
differential_diagnoses:
- name: Severe combined immunodeficiency
  description: >-
    VODI can initially resemble severe combined immunodeficiency because of
    early opportunistic infections and profound immune dysfunction.
  distinguishing_features:
  - Hepatic veno-occlusive disease and hepatic fibrosis favor VODI.
  - Biallelic SP110 variants support VODI, and TREC-based newborn SCID screening may miss it.
  disease_term:
    preferred_term: severe combined immunodeficiency
    term:
      id: MONDO:0015974
      label: severe combined immunodeficiency
  evidence:
  - reference: PMID:22982295
    reference_title: "Hepatic veno-occlusive disease with immunodeficiency (VODI): first reported case in the U.S. and identification of a unique mutation in Sp110."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Familial hepatic veno-occlusive disease with immunodeficiency (VODI,
      OMIM: 235550), a rare form of severe combined immune deficiency
    explanation: >-
      This directly supports severe combined immunodeficiency as an important
      overlapping diagnosis that VODI may mimic.
- name: Hepatic veno-occlusive disease
  description: >-
    Isolated hepatic veno-occlusive disease or sinusoidal obstruction syndrome
    overlaps with the liver phenotype of VODI but lacks the syndromic immune
    defect.
  distinguishing_features:
  - Severe hypogammaglobulinemia and combined immunodeficiency favor VODI.
  - Identification of biallelic SP110 variants distinguishes the inherited syndromic form.
  disease_term:
    preferred_term: hepatic veno-occlusive disease
    term:
      id: MONDO:0019514
      label: hepatic veno-occlusive disease
  evidence:
  - reference: PMID:16648851
    reference_title: Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      severe hypogammaglobulinemia, combined T and B cell immunodeficiency,
      absent lymph node germinal centers, absent tissue plasma cells and
      hepatic veno-occlusive disease
    explanation: >-
      This supports distinguishing the inherited immunodeficiency syndrome from
      isolated hepatic veno-occlusive disease.
clinical_trials: []
datasets: []
references:
- reference: PMID:20301448
  title: "Hepatic Veno-Occlusive Disease with Immunodeficiency."
  tags:
  - GeneReviews
  findings: []
notes: >-
  Curation used the Asta deep-research report in research/ and supplemented it
  with disease-specific SP110/VODI primary sources and GeneReviews. No
  disease-specific public datasets or registered interventional trials were
  identified from the supporting material curated here.

📚

References & Deep Research

References

1

PMID:20301448

Hepatic Veno-Occlusive Disease with Immunodeficiency.

No top-level findings curated for this source.

Deep Research

1

Asta ▸

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hepatic veno-occlusive disease-immunodeficiency syndrome. Core disease mec...

Asta Scientific Corpus Retrieval 19 citations 2026-04-21T17:02:51.212922

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hepatic veno-occlusive disease-immunodeficiency syndrome. Core disease mec...

This report is retrieval-only and is generated directly from Asta results.

Papers retrieved: 19
Snippets retrieved: 20

Relevant Papers

[1] Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

Authors: C. Mastroianni, M. Lichtner, C. Mascia, P. Zuccalà, V. Vullo
Year: 2014
Venue: International Journal of Molecular Sciences
URL: https://www.semanticscholar.org/paper/22de2dd977b7f1302fb6dc29a174487ab88df54a
DOI: 10.3390/ijms15069184
PMID: 24865485
PMCID: 4100089
Citations: 96
Influential citations: 6
Summary: The evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV are discussed.
Evidence snippets:
Snippet 1 (score: 0.481) > Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

[2] Ten Cases of Hepatic Sinuses Obstruction Syndrome Caused by Sedum Uizoon

Authors: X. Wang, Wang Yg
Year: 2018
Venue: journal of Clinical Case Reports
URL: https://www.semanticscholar.org/paper/dc9e5e8ac06d4d77ef98bb9f5d3369a3e10ecee4
DOI: 10.4172/2165-7920.10001135
Summary: The clinical characteristics of HSOS caused by sedum uizoon were analyzed in detail, which provided clinical data for the diagnosis and treatment and the mechanism of the disease in the future.
Evidence snippets:
Snippet 1 (score: 0.469) > Hepatic sinuses obstruction syndrome (HSOS) also known as hepatic venule syndrome, refers to the injury of central lobe and sub-lobular vein of hepatic lobule, resulting in intrahepatic posterior sinus portal hypertension caused by lumen stenosis or occlusion. Currently the pathogenesis is not clear. It may be related to the drug, immunity and inflammation of the liver vein endothelial cells. The clinical manifestations are hepatomegaly, right upper abdominal pain, jaundice and ascites, with a high risk of mortality and poor prognosis for characteristics. Occurs because of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), adjuvant or neoadjuvant chemotherapy containing oxaliplatin for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, taking herbal remedies containing pyrrolizidine alkaloid and the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). In this paper, the clinical characteristics of HSOS caused by sedum uizoon were analyzed in detail, which provided clinical data for the diagnosis and treatment and the mechanism of the disease in the future.

[3] Sinusoidal Obstruction Syndrome Post-allogeneic Transplantation: A Complex Multisystem Challenge

Authors: Tomas Escobar Gil, Sushrruti Varatharaj, S. Rosenberg, G. J. Aguilar, David Santistevan et al.
Year: 2025
Venue: Cureus
URL: https://www.semanticscholar.org/paper/cce816feb22a5c8d5488aada4604332db94ed4ba
DOI: 10.7759/cureus.80078
PMID: 40190874
PMCID: 11970208
Summary: The case of a 41-year-old female with chronic myeloid leukemia (CML) in blast crisis who underwent haploidentical allogeneic stem cell transplantation highlights the need for early intervention, a tailored risk-benefit assessment of defibrotide, and multidisciplinary critical care strategies for high-risk patients.
Evidence snippets:
Snippet 1 (score: 0.465) > Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a rare but severe complication of hematopoietic stem cell transplantation (HSCT) caused by endothelial injury within the hepatic sinusoids [1,2]. Clinically, it manifests as sinusoidal congestion, hepatomegaly, and hyperbilirubinemia, typically within three weeks after transplantation [3,4]. Several factors increase the risk of SOS, including myeloablative conditioning regimens, haploidentical donors, and preexisting liver dysfunction [5,6]. > The pathophysiology of SOS is multifactorial, involving endothelial injury, activation of coagulation pathways, inflammatory cytokines, and complement system dysregulation [3]. These mechanisms suggest potential targets for adjunct therapies, such as complement inhibitors, anti-inflammatory agents, or endothelial-protective strategies, which warrant further investigation [7,8]. For survivors of SOS, long-term complications, such as chronic liver disease and portal hypertension, remain significant concerns, with consistent follow-up becoming an important factor in the care of these patients after the event [1]. This case highlights the complexity of SOS in a post-transplant setting, emphasizing the challenges in diagnosis, therapeutic decision-making, and multidisciplinary care. Through this case, we aim to illustrate the clinical course, diagnostic criteria, and therapeutic challenges associated with SOS, contributing to a deeper understanding of this serious complication in hematopoietic stem cell transplantation.

[4] Lipophagy: Molecular Mechanisms and Implications in Hepatic Lipid Metabolism.

Authors: Sai Feng, Zeao Sun, Xiao Jia, Lingyun Li, Yijian Wu et al.
Year: 2023
Venue: Frontiers in bioscience
URL: https://www.semanticscholar.org/paper/05073e2380c667f7bdf193e0c71a30a8cfbdf55e
DOI: 10.31083/j.fbl2801006
PMID: 36722271
Citations: 19
Influential citations: 1
Summary: Increasing evidence suggests that lipophagy is an effective method to resolve liver diseases because of its role in lipid metabolism and the interaction betweenlipophagy and hepatic lipid metabolism.
Evidence snippets:
Snippet 1 (score: 0.430) > The liver is the central organ of lipid metabolism and plays a vital role in cellular metabolisms, such as lipid digestion, absorption, transport, and decomposition [1].Chronically disturbed hepatic metabolism may lead to obesity and metabolic syndrome, causing non-alcoholic fatty liver disease (NAFLD) [2].Approximately 1 in 30 patients diagnosed with NAFLD develops cirrhosis or a liverassociated complication [3].Autophagy plays a crucial role during hepatic lipid metabolism.Diet, environment, and drugs strongly affect hepatic lipid metabolism through autophagy [4].Therefore, a further understanding of the specific molecular mechanisms of autophagy and various cell types involved has been deeply explored.The current article reviews the main pathways and regulatory mechanisms of hepatic autophagy and the related effects on lipid metabolism.

[5] In vitro systems to study inborn errors of immunity using human induced pluripotent stem cells

Authors: Eirini Nikolouli, Janne Reichstein, G. Hansen, N. Lachmann
Year: 2022
Venue: Frontiers in Immunology
URL: https://www.semanticscholar.org/paper/50f330ee9584168734b8cc8a22dc702c4cbe8ec5
DOI: 10.3389/fimmu.2022.1024935
PMID: 36466870
PMCID: 9713844
Citations: 1
Summary: This review aims to provide an overview of the current available in vitro models used to study IEI and which could lay the foundation for new therapeutic approaches and elaborate in particular on the use of induced pluripotent stem cell-based systems.
Evidence snippets:
Snippet 1 (score: 0.423) > of drug-resistant pathogens, which can cause lifethreatening infections. In some cases, like in the severe combined immunodeficiency (SCID) syndrome, allogenic hematopoietic stem cell transplantation (HSCT) (or autologous HSC-gene therapy) is the only curative therapy (6,7). However, HSCT always lurks the risk of immunological rejection or development of graft versus host disease with devastating consequences for the patient, pointing towards the need of suitable alternatives. > For these reasons, more targeted therapeutic approaches, which can directly modulate specific cell types or intracellular pathways, are preferred. These approaches include the use of specific inhibitors or biologics (antibodies or recombinant proteins). For the safe use of these emerging therapeutic agents, a detailed study of the pathophysiological mechanisms of the diseases is necessary. Given the rarity of IEI and the technical difficulties (obtaining sufficient samples from children or the low number of affected cells), the study of IEI-related diseases remains challenging. Thus, the development of novel systems to unravel the cellular and molecular mechanisms involved in the pathophysiology of the various IEI is of great importance.

[6] Basic and Clinical Advances in Chronic Liver Inflammation

Authors: H. Enomoto, A. Tamori, H. Yoshiji, E. Seki
Year: 2016
Venue: Mediators of Inflammation
URL: https://www.semanticscholar.org/paper/3d41abce2962c7757c197fb58e2c5ada322d6fb6
DOI: 10.1155/2016/1571457
PMID: 27006527
PMCID: 4783579
Summary: This special issue is proposed to provide recent basic and clinical findings in chronic liver inflammation and its complications, and introduces papers regarding the complications of progressed liver diseases.
Evidence snippets:
Snippet 1 (score: 0.423) > Continuous liver inflammation causes fibrotic changes and leads to the development of liver cirrhosis and liver cancer. Recent biological and medical advances have clarified the mechanisms of chronic liver inflammation and succeeded in providing new therapies for various liver diseases. We proposed this special issue to provide recent basic and clinical findings in chronic liver inflammation and its complications. > Regarding the diagnosis and treatment of liver inflammation, A. Tsutsui et al. showed the clinical utility of the Digestive Disease Week Japan 2004 (DDW-J) scale, which has been used as an objective diagnostic tool for drug-induced liver injury in Japan. A. Tamori et al. reviewed remarkable progression in antiviral treatments for hepatitis C virus (HCV), including DAAs (direct-acting antivirals or direct antiviral agents). > We also introduce papers regarding the complications of progressed liver diseases in this special issue. The prognoses of cirrhotic patients are highly dependent on their liver function, and A. Hassan et al. showed that L-carnitine administration helps maintain and improve liver functions after transarterial chemoembolization. Additionally, malnutrition is a frequently observed complication which is known to be associated with a poor prognosis. Y. Osaki and H. Nishikawa reviewed the nutritional problems of cirrhosis, focusing on a recent hot topic “sarcopenia.” Portal hypertension is a major problem along with the progression of chronic liver disease. The paper by K. Kotani et al. suggested the association of the immune system with the development of portal hypertension. Hepatocellular carcinoma is also a prognosis-determining complication of patients with chronic liver inflammation. K. Shindo et al. showed the clinical utility of a semiannual imaging surveillance program in patients without hepatitis viral infection. > With regard to the basic mechanisms of chronic liver inflammation, H. Tsutsui et al. reviewed the roles of IL-1 family cytokines in the development of various liver diseases, including IL-1 family cytokine-mediated molecular and cellular networks. Coinfection of HCV and human immunodeficiency virus (HIV) cooperatively leads to the progression of liver disease. Along this viewpoint, the paper by M. C. Liberto et al., which described the specific

[7] Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

Authors: Hao Xiong, Jinsheng Guo
Year: 2025
Venue: Pharmaceuticals
URL: https://www.semanticscholar.org/paper/76e92127053136900f7e3f10e2c9278251ced5d2
DOI: 10.3390/ph18040507
PMID: 40283943
PMCID: 12030350
Citations: 8
Summary: HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects.
Evidence snippets:
Snippet 1 (score: 0.422) > Significant progress has been made in elucidating the cellular and molecular mechanisms of liver fibrosis; however, only a few findings have been successfully translated into clinical applications. Firstly, the high cost of drug development and target validation necessitates prolonged timelines and substantial financial investment. Secondly, as regulatory requirements become more stringent, there is an increasing demand for drugs with well-defined clinical efficacy and safety profiles. Moreover, the efficacy observed in animal models often fails to fully translate to clinical settings due to differences in pharmacokinetics, extracellular matrix (ECM) cross-linking, and disease pathophysiology. Despite advancements in anti-fibrotic drug development, accurately identifying ideal noninvasive biomarkers for fibrotic activity and establishing consensus on optimal clinical endpoints remain significant challenges [113,114]. > Currently, addressing the underlying cause remains the only proven strategy to halt or reverse liver fibrosis progression, while the development of effective anti-fibrotic therapies continues to pose a major challenge in liver disease management. Over the past few decades, substantial progress has been made in elucidating the cellular and molecular mechanisms underlying liver fibrosis. Liver fibrosis is a complex pathological change involving multiple cells, factors, and pathways, and the study of the cellular and molecular mechanisms of its occurrence and development provides an important theoretical basis and therapeutic target for clinical drug development. It is anticipated that improved animal models and well-designed clinical trials will facilitate the successful translation of anti-fibrotic research into effective clinical treatments in the near future.

[8] Hepatic veno-occlusive disease-immunodeficiency syndrome

Authors: Unknown authors
Year: 2020
Venue: Definitions
URL: https://www.semanticscholar.org/paper/ca0179047b364e90ddc74672dc7abb73baacfa72
DOI: 10.32388/u9la32
Summary: Hepatic veno-occlusive disease-immunodeficient syndrome is characterized by the association of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic venO-OCclusive disease.
Evidence snippets:
Snippet 1 (score: 0.419) > Hepatic veno-occlusive disease-immunodeficiency syndrome is characterized by the association of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease.
Snippet 2 (score: 0.410) > Hepatic veno-occlusive disease-immunodeficiency syndrome

[9] Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies

Authors: Jeysson E Mejía-Guzmán, Ramón A. Belmont-Hernández, Norberto C. Chávez-Tapia, M. Uribe, N. Nuño-Lámbarri
Year: 2025
Venue: International Journal of Molecular Sciences
URL: https://www.semanticscholar.org/paper/4c63d1bff27c7cfbe5c3091c5eb3445a0a04f186
DOI: 10.3390/ijms26072959
PMID: 40243565
PMCID: 11988898
Summary: This review delves into the molecular mechanisms driving MASLD pathogenesis, including dysregulation of lipid metabolism, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota alterations.
Evidence snippets:
Snippet 1 (score: 0.403) > MASLD and MASH are increasingly recognized as central components of the broader cardiometabolic disease spectrum. The recently proposed Cardiovascular-Renal-Hepatic-Metabolic syndrome expands upon the earlier Cardiovascular-Kidney-Metabolic model by integrating the liver as a critical organ involved in the interconnected pathophysiology linking metabolic, cardiovascular, renal, and hepatic health. This holistic framework acknowledges the bidirectional interactions between MASLD and other cardiometabolic disorders, emphasizing shared mechanisms such as meta-inflammation, adipokine dysregulation, insulin resistance, oxidative stress, and neurohormonal activation. By incorporating MASLD into the broader cardiometabolic landscape, the CRHM syndrome offers a clinically relevant and scientifically grounded framework to address the global burden of cardiometabolic disorders more effectively [16]. > Regarding oncological outcomes, MASLD has also been associated with an elevated risk of both hepatic and extrahepatic cancers. While the primary hepatic cancers are often driven by cirrhosis, an increased risk has also been observed in patients with the condition. Furthermore, MASLD has also been linked to extrahepatic malignancies, particularly colorectal cancer, where the risk is approximately 50% higher compared to patients without MASLD [14,17]. > Understanding the molecular pathophysiology and diverse clinical manifestations of these conditions is essential for effective treatment. Early diagnosis and targeted molecular interventions addressing the underlying mechanisms can halt disease progression and significantly improve patient outcomes.

[10] Coagulation disturbances in paediatric patients with hepatic veno-occlusive disease after stem cells transplantation.

Authors: D. Jevtić, D. Vujic, Željko Zečević, D. Veljković, S. Gazikalović et al.
Year: 2010
Venue: Srpski arhiv za celokupno lekarstvo
URL: https://www.semanticscholar.org/paper/3ea4487128c4d63501c2fc57baa3962200940ec1
DOI: 10.2298/SARH10S1033J
PMID: 20229680
Citations: 4
Summary: It is suggested that monitoring coagulation parameters levels in the first five days from the establishment of diagnosis may have a significant predictive value for VOD outcome.
Evidence snippets:
Snippet 1 (score: 0.403) > Liver veno-occlusive disease (VOD) is a clinical syndrome characterized by hepatomegaly, fluid retention and hyperbilirubinaemia [1]. It is a serious complication after high doses of chemotherapy and/or radiotherapy and immunosuppressive treatment. Also, it is an early complication after stem cells transplantation (SCT), one of the most frequent complication and one of the leading causes of death in this group of patients [2]. In paediatric population the incidence of VOD is between 5-40%, mortality rate around 40% and, according to the recent studies, it is several times higher comparing with adults [2,3]. > The precise mechanism of VOD and the place of damage are not completely clear yet; it is, most probably, the result of sinusoidal endothelial cell damage followed by hepatocyte necrosis and coagulation activation. All these thee processes are highly increased after being followed by cytokine activation, especially tumour necrosis factor α and interleukin 1β [1]. First pathohistological findings have been seen in zone 3 of hepatic acinus as a progressive and concentric narrowing of small intrahepatic venules associated with necrosis of hepatocytes in the centrilobular areas. A lasting sinusoidal obstruction with cell detritus and erythrocytes consecutively leads to sinusoidal fibrosis and obliteration [4]. > The diagnosis of VOD relies on the combination of certain clinical signs, and most of transplantation teams use Seattle or Baltimore criteria, which are similar. The Seattle criteria requires two of the following three physical or laboratory findings: 1) jaundice or bilirubin level >34 μmol\l; 2) hepatomegaly or right upper quadrant pain of liver origin or; 3) sudden weight gain of more than 5% above baseline caused by either fluid accumulation or ascites [5]. For clinical practise it is very useful to add ultrasound findings of gallbladder thickening of more than 4 mm and platelet transfusion dependency together with the mentioned well known clinical signs [6].

[11] 18O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

Authors: E. Nemutlu, Song Zhang, N. Juranic, A. Terzic, S. Macura et al.
Year: 2012
Venue: Croatian Medical Journal
URL: https://www.semanticscholar.org/paper/880f053c7f060db4b990e447d0a22c4b69372ddb
DOI: 10.3325/cmj.2012.53.529
PMID: 23275318
PMCID: 3541579
Citations: 28
Summary: The potential use of dynamic phosphometabolomic platform for disease diagnostics currently under development at Mayo Clinic is described and discussed briefly.
Evidence snippets:
Snippet 1 (score: 0.401) > Living cells represent an integrated and interacting network of genes, transcripts, proteins, small signaling molecules, and metabolites that define cellular phenotype and function. Traditionally the focus of biomedical research was on individual genes, single protein targets, single metabolites, and metabolic or signaling pathways. This "molecular reductionist" paradigm was based on the assumption that identifying genetic variations and molecular components would lead to discovery of cures for human diseases. However, most of diseases are complex and multi-factorial and the disease phenotype is determined by the alterations of multiple genes, pathways, proteins and metabolites (at cellular, tissue, and organismal levels). Therefore, an integrated "omics" approach is more viable direction for uncovering alterations in metabolic networks, disease mechanisms, and mechanisms of drug effects. > Recent advent of large-scale metabolomics and fluxomic (metabolite dynamics and metabolic flux analysis) completed the "omics revolution" (Figure 1), where genomics, transcriptomics, proteomics, metabolomics, and fluxomics all together complement phenotype determination of living organism. Such integrated "omics" cascades provide a framework for advances in system and network biology, integrative physiology, and system medicine as well as system pharmacology and regenerative medicine. Noteworthy is the "reverse omic" approach or "metabolomicsinformed pharmacogenomics, " where discovery of specific metabolite changes have led to discovery of genetic alterations (2). Therefore, bringing new "omics" technologies to clinical practice will improve disease diagnostics and treatment by targeting drugs and procedures for each unique transcriptomic and metabolomic profiles.

[12] Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

Authors: S. Putta, B. Young, J. Levine, R. Reshef, R. Nakamura et al.
Year: 2022
Venue: Transplantation and cellular therapy
URL: https://www.semanticscholar.org/paper/6f56766841865b8c6fdb47f19384cd61b9a4e77b
DOI: 10.1016/j.jtct.2022.11.024
PMID: 36574581
PMCID: 10116945
Citations: 7
Summary: Multivariate analysis suggests that a combination of up to 5 protein biomarkers may provide a prognostic tool for identifying patients at risk for VOD/SOS shortly after HCT.
Evidence snippets:
Snippet 1 (score: 0.399) > Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication observed after hematopoietic cell transplantation (HCT) often characterized by ascites, hepatomegaly, weight gain, and hyperbilirubinemia [1,2]. Severe VOD/SOS with multiorgan dysfunction is associated with high mortality (>80%) if untreated [3]. The incidence of VOD/SOS following HCT ranges from 5% to 60% [3,4] and varies depending on clinical risk factors, such as conditioning regimen intensity, type of transplant, graft-versus-host disease (GVHD) prophylaxis, and such patient characteristics as age, advanced malignancy, and history of hepatitis B or C infection [4][5][6]. > The pathogenesis of VOD/SOS is complex, but damage to the endothelial cells (ECs) lining hepatic sinusoids resulting from accumulation of toxic metabolites produced by HCT conditioning is likely the inciting event [5]. EC injury induces the expression of procoagulant factors, inflammatory cytokines, and metalloproteinases and the release of heparanase, which results in a loss of cytoskeletal integrity, opening of the endothelial paracellular pathways [7,8], and extravasation of cellular and extracellular debris into the space of Disse. This in turn leads to extraluminal compression of sinusoidal vessels [7,9] and culminates in postsinusoidal hypertension, reduction or reversal of sinusoidal flow, and ultimately sinusoidal obstruction and/or central vein occlusion, the pathologic hallmarks of VOD/SOS [5]. > VOD/SOS typically manifests within 3 weeks after HCT but occurs later in approximately 20% of patients [10,11].

[13] Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment

Authors: A. Gruevska, Ángela B. Moragrega, A. Cossarizza, J. Esplugues, A. Blas-García et al.
Year: 2021
Venue: Cells
URL: https://www.semanticscholar.org/paper/dfb9e730d9161be4832d28d9affecd8eef223c4e
DOI: 10.3390/cells10020410
PMID: 33669403
PMCID: 7920460
Citations: 14
Summary: The evidence and potential mechanisms involved in the apoptosis of hepatocytes induced by HIV, HIV-encoded proteins, or cART are discussed.
Evidence snippets:
Snippet 1 (score: 0.397) > Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infections, HIV itself and the adverse effects of cART are the main factors that contribute to hepatic cell injury, inflammation, and fibrosis. Among the molecular mechanisms that are activated in the liver during HIV infection, apoptotic cell death of hepatocytes stands out as a key pathogenic player. In this review, we will discuss the evidence and potential mechanisms involved in the apoptosis of hepatocytes induced by HIV, HIV-encoded proteins, or cART. Some antiretroviral drugs, especially the older generation, can induce apoptosis of hepatic cells, which occurs through a variety of mechanisms, such as mitochondrial dysfunction, increased production of reactive oxygen species (ROS), and induction of endoplasmic reticulum (ER) stress and unfolded protein response (UPR), all of which ultimately lead to caspase activation and cell death.

[14] The potential roles of gut microbiome in porto-sinusoidal vascular disease: an under-researched crossroad

Authors: Yangjie Li, Lingna Lyu, Huiguo Ding
Year: 2025
Venue: Frontiers in Microbiology
URL: https://www.semanticscholar.org/paper/7fc2f5ae990d46892b846143a3a862fe435360f2
DOI: 10.3389/fmicb.2025.1556667
PMID: 40099185
PMCID: 11911366
Citations: 1
Summary: The current understanding of the gut microbiome's potential role in the pathogenesis of hepatic microvascular abnormalities and thrombosis is summarized and the insights into gut microbiota and their potential influence on the onset and progression of PSVD may pave the way for new diagnostic, prognostic, and therapeutic strategies.
Evidence snippets:
Snippet 1 (score: 0.395) > The diagnosis of PSVD remains challenging, which primarily relies on clinical signs of portal hypertension combined with specific histological features involving the porto-sinusoidal vascular abnormalities (obliterative portal venopathy, portal tract hypervascularization, and abnormal periportal vessels) as well as parenchymal abnormalities (Gioia et al., 2024;De Gottardi et al., 2022). Moreover, the pathophysiology responsible for PSVD is complex and hinders the development of treatments capable of altering the natural history of the disease. A better insight into the biological processes and pathophysiological mechanisms involved in PSVD is essential for identifying disease drivers and developing new diagnostic and therapeutic strategies. > Gut microbiome plays critical roles in the development of several vascular disease phenotypes by activating vascular endothelial cells, platelets, and innate immune cells (Hasan et al., 2020). Since the liver yields most of its blood supply via the portal circulation, the hepatic microcirculation constantly encounters gut-derived components, metabolites, and signals. These factors can induce changes in the liver sinusoidal endothelium, affecting the immune partitioning of the sinusoids and influencing portal hypertension (Kiouptsi et al., 2023). Although the exact pathogenesis of PSVD remains unclear, it is hypothesized to result from injuries and occlusion of the intrahepatic portal microvasculature, leading to increased resistance to portal blood flow and subsequent presinusoidal type of portal hypertension (Jin and Choi, 2023). Predisposing conditions of PSVD are related to immune disorders, infections, prothrombotic conditions, congenital or hereditary defects, drug exposure, and inherited vascular remodeling disorders (Kmeid et al., 2021). The link between gut microbiome, portal hypertension, and predisposing conditions of PSVD have supported that gut microbiota translocation into the sinusoids may impact on the pathophysiology of PSVD (Fiordaliso et al., 2023).

[15] LifeTime and improving European healthcare through cell-based interceptive medicine

Authors: N. Rajewsky, G. Almouzni, S. Gorski, S. Aerts, I. Amit et al.
Year: 2020
Venue: Nature
URL: https://www.semanticscholar.org/paper/d626a4acb560c1ef16ea394cb4dccf277882d119
DOI: 10.1038/s41586-020-2715-9
PMID: 32894860
PMCID: 7656507
Citations: 138
Influential citations: 2
Summary: The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe over the next decade.
Evidence snippets:
Snippet 1 (score: 0.393) > , a major challenge is a lack of understanding of the early events in disease onset to enable the development of disease-modifying therapies. The lack of access to longitudinal samples from patients necessitates the establishment of cohorts of patient-derived disease models to understand the cellular heterogeneity associated with disease. The discovery of pathways and biomarkers that will allow the stratification of patients on the basis of the cellular mechanisms that drive a disease will make it possible to design new clinical trials to reevaluate drugs that were previously tested without such stratification, and to broaden the drug target portfolio. > As seen during the coronavirus disease 2019 (COVID-19) pandemic, it is important to be able to understand infection mechanisms and the host response in order to rapidly identify the most likely effective treatment for an infection. At the same time, the continuous rise of antimicrobial resistance requires the discovery of new therapeutic strategies. A key medical challenge for infectious diseases is to understand the cellular response to infections and to develop precision, immune-based therapeutic strategies to combat infections. > Chronic inflammatory diseases impose a high burden owing to their long-term debilitating consequences, which result from the structural destruction of affected organs or tissues. Current therapies treat the symptoms but do not cure or fully control the chronic inflammatory pathophysiology. While different targeted therapies exist, they are expensive and their success is limited by high rates of non-response to treatment. Consequently, there is an urgent need to explore and understand how cellular heterogeneity contributes to the pathology of inflammatory diseases 61 and how this relates to the predicted course of disease and the response of a patient to one of the numerous available therapies. > Many cardiovascular and metabolic diseases lack effective therapies owing to a lack of knowledge of their underlying causes and the link between abnormal cardiac cell structure or function and pathophysiology. The identified medical priority is to understand the cellular and molecular mechanisms involved, in order to enable early diagnosis and the design of new mechanism-based therapies for precise clinical treatment. > The LifeTime disease roadmaps can be divided broadly into three phases 7 : first, immediate research into the identified medical challenges using established, scaled single-cell technologies, computational tools and disease models; second, the development of new technologies that are required

[16] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

Authors: M. Uzti̇mür, C. N. Ünal, Gurler Akpinar
Year: 2025
Venue: Journal of Veterinary Internal Medicine
URL: https://www.semanticscholar.org/paper/4b9c488b5dbd65d7b26fd2ad9aed70e8c4b59942
DOI: 10.1111/jvim.70139
PMID: 40492724
PMCID: 12150350
Summary: Understanding the serum proteome profiles of goats with pregnancy toxemia might help identify the proteomes and pathways responsible for the development of this disease and improve diagnosis and treatment.
Evidence snippets:
Snippet 1 (score: 0.392) > The pathophysiology and progression of this disease are not fully understood. > Traditional biomedical research has focused on the analysis of single genes, proteins, metabolites, or metabolic pathways in diseases. This molecular reductionist approach is based on the assumption that identifying genetic variations and molecular components will lead to new treatments for diseases [13][14][15][16]. However, many diseases are complex and multifactorial, and in order to determine the phenotype of such diseases, it is necessary to understand the changes that occur in more than one gene, pathway, protein, or metabolite at the cellular, tissue, and organismal levels [17][18][19]. Therefore, in recent years, proteomics, as one field of multi-omics technologies, has helped in evaluating the complex pathogenetic mechanisms of different diseases from a broad perspective and has made substantial contributions [20,21]. In veterinary medicine, proteomic analysis of metabolic diseases such as ketosis [16], hypocalcemia [22], and fatty liver [23] in dairy cows has contributed valuable insights for the definition of new pathophysiological pathways and new diagnosis and treatment protocols for these diseases. The proteomic approach can contribute importantly to a broad and detailed understanding of the changes that occur at the organismal level associated with the increase in BHBA concentration in goats with pregnancy toxemia. Our aim was to evaluate the serum protein profiles of goats with SPT or CPT using proteomic techniques to determine the proteomic profiles of these animals and to identify the relevant pathophysiological mechanisms.

[17] Pathology Competencies in Medical Education and Educational Cases: Update 2023

Authors: B. Knollmann-Ritschel, A. Huppmann, M. Borowitz, R. Conran
Year: 2023
Venue: Academic Pathology
URL: https://www.semanticscholar.org/paper/4ffbccfbf055a43c6344d7de3c8f40ded1bbccd0
DOI: 10.1016/j.acpath.2023.100086
PMID: 37496887
PMCID: 10366624
Citations: 17
Summary: The learning goals and learning objectives of the PCME that were first published in 2017 have been carefully revised and updated and will allow for continued linking of previous and new educational cases to the revised learning objectives.
Evidence snippets:
Snippet 1 (score: 0.390) > Apply knowledge of basic mechanisms of immunology to explain how dysfunction can produce cellular injury, acute and chronic inflammation, autoimmunity, allergic reactions, and susceptibility to infection; how these changes affect organ function and the health of the organism; and how therapeutic intervention can mitigate these effects. Objective IM1.5: Complement. Discuss how the complement cascade is activated, the role its activation plays in both inflammation and cellular cytotoxicity, and how abnormalities in complement function can produce disease. > Objective IM1.6: Immune Tolerance. Define immunological tolerance and describe the role that failure of tolerance plays in the development of autoimmune diseases. > Objective IM1.7: Human Leukocyte Antigen (HLA). Discuss the structure and function of human histocompatibility antigens and describe the role of this system in both transplantation and susceptibility to certain diseases. > Objective IM1.8: Tissue Transplantation. Discuss the complications of tissue transplantation, including the risk of infection and neoplasia, and the pathophysiology and clinicopathologic findings of hyperacute, acute, and chronic rejection. > Objective IM1.9: Primary Immunodeficiencies. Compare and contrast the genetic basis and inheritance patterns of the well-defined primary immunodeficiency syndromes, discuss the pathogenesis and clinical manifestations of these disorders, and describe therapeutic interventions that can mitigate or correct them. > Objective IM1.10: Secondary Immune Deficiencies. Describe the etiology, mechanisms of action, and possible clinical consequences of secondary immune deficiencies. > Objective IM1.11: Bone Marrow Transplantation. Discuss common complications of bone marrow allograft transplantation, including the pathophysiologic and clinicopathologic features of acute and chronic graftversus-host disease.

[18] Editorial: The Role of Microbiota in the Onset and Development of Intestine and Liver Diseases and Cancer: Molecular and Cell Mechanisms

Authors: F. Andreola, Camilla Moliterni, Andrea Quagliariello, F. Scaldaferri, M. Fidaleo
Year: 2022
Venue: Frontiers in Cell and Developmental Biology
URL: https://www.semanticscholar.org/paper/833e6db5d680891640f1470827bb4281059ee288
DOI: 10.3389/fcell.2022.852188
PMID: 35356278
PMCID: 8959644
Summary: Liver Failure Group, Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, United Kingdom and Sapienza University of Rome, Rome, Italy.
Evidence snippets:
Snippet 1 (score: 0.388) > The Role of Microbiota in the Onset and Development of Intestine and Liver Diseases and Cancer: Molecular and Cell Mechanisms > In the last decades, numerous studies highlighted the huge taxonomic and functional complexity that characterizes the human microbiota, demonstrating its role in several physiological processes necessary for host survival. This evidence supports the hypothesis that the microbiota constitutes an "essential organ" instead of a "simple" conglomerate of microbial symbionts. Furthermore, findings point out a mutual host-microbiota interaction, whose imbalance can trigger dysbiosis and, in turn, the onset of illnesses or vice versa. In the latter case, dysbiosis can magnify sicknesses. Several factors can alter microbiota homeostasis and the present Research Topic collects seven reviews and four original contributions focused on the cellular and molecular mechanisms involved in the interaction between host and microbiota which can help to unravel the possible cause of disease and find new therapeutic approaches. Soffientini et al. and Bi et al. describe new cellular and molecular mechanisms that strengthen the role of the gut microbiota in pathogenesis and progression of liver diseases. > Using a mouse model, Soffientini et al. reported that the deficiency of caspase-11, a protease involved in the intracellular LPS sensing and triggering cell death pathways, gives protection against multi-organ injury induced by low-dose injection of LPS in CCl4-induced hepatic fibrosis. Furthermore, they found that high levels of the human orthologue, caspase-4, in the liver of patients with acute decompensation of cirrhosis is correlated with the degree of injury and clinical outcome. Overall, these data showed for the first time a causal relationship between translocation of gut-derived bacterial products and multi-organ injury in cirrhosis. > Bi et al. provided theoretical support for future clinical practice, discussing the more recent findings regarding the immuno-molecular mechanisms of the gut microbiota and their metabolites in the occurrence and development of liver cancer. They pointed out that a balanced composition in the gut microbiota is able to improve chemotherapy treatment in liver cancer and to reduce adverse reactions.

[19] Hepatic wound repair

Authors: M. Parola, M. Pinzani
Year: 2009
Venue: Fibrogenesis & Tissue Repair
URL: https://www.semanticscholar.org/paper/1fdf786492f33c80ec4814220e66012ca1da8f98
DOI: 10.1186/1755-1536-2-4
PMID: 19781064
PMCID: 2760508
Citations: 61
Influential citations: 1
Summary: Emerging mechanisms and concepts related to liver fibrogenesis may significantly contribute to clinical management of patients affected by CLDs, thus extending the complication-free patient survival time and reducing the need for liver transplantation.
Evidence snippets:
Snippet 1 (score: 0.387) > BackgroundHuman chronic liver diseases (CLDs) with different aetiologies rely on chronic activation of wound healing that represents the driving force for fibrogenesis progression (throughout defined patterns of fibrosis) to the end stage of cirrhosis and liver failure.IssuesFibrogenesis progression has a major worldwide clinical impact due to the high number of patients affected by CLDs, increasing mortality rate, incidence of hepatocellular carcinoma and shortage of organ donors for liver transplantation.Basic science advancesLiver fibrogenesis is sustained by a heterogeneous population of profibrogenic hepatic myofibroblasts (MFs), the majority being positive for α smooth muscle actin (αSMA), that may originate from hepatic stellate cells and portal fibroblasts following a process of activation or from bone marrow-derived cells recruited to damaged liver and, in a method still disputed, by a process of epithelial to mesenchymal transition (EMT) involving cholangiocytes and hepatocytes. Recent experimental and clinical data have identified, at tissue, cellular and molecular level major profibrogenic mechanisms: (a) chronic activation of the wound-healing reaction, (b) oxidative stress and related reactive intermediates, and (c) derangement of epithelial-mesenchymal interactions.Clinical care relevanceLiver fibrosis may regress following specific therapeutic interventions able to downstage or, at least, stabilise fibrosis. In cirrhotic patients, this would lead to a reduction of portal hypertension and of the consequent clinical complications and to an overall improvement of liver function, thus extending the complication-free patient survival time and reducing the need for liver transplantation.ConclusionEmerging mechanisms and concepts related to liver fibrogenesis may significantly contribute to clinical management of patients affected by CLDs.

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Relevant Papers

[1] Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

[2] Ten Cases of Hepatic Sinuses Obstruction Syndrome Caused by Sedum Uizoon

[3] Sinusoidal Obstruction Syndrome Post-allogeneic Transplantation: A Complex Multisystem Challenge

[4] Lipophagy: Molecular Mechanisms and Implications in Hepatic Lipid Metabolism.

[5] In vitro systems to study inborn errors of immunity using human induced pluripotent stem cells

[6] Basic and Clinical Advances in Chronic Liver Inflammation

[7] Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

[8] Hepatic veno-occlusive disease-immunodeficiency syndrome

[9] Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies

[10] Coagulation disturbances in paediatric patients with hepatic veno-occlusive disease after stem cells transplantation.

[11] 18O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

[12] Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

[13] Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment

[14] The potential roles of gut microbiome in porto-sinusoidal vascular disease: an under-researched crossroad

[15] LifeTime and improving European healthcare through cell-based interceptive medicine

[16] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

[17] Pathology Competencies in Medical Education and Educational Cases: Update 2023

[18] Editorial: The Role of Microbiota in the Onset and Development of Intestine and Liver Diseases and Cancer: Molecular and Cell Mechanisms

[19] Hepatic wound repair

Notes