SUPERStudy: Autoimmune Hepatitis (AIH)

By usmlevideoss

SUPERStudy: Autoimmune Hepatitis (AIH)

Introduction

Autoimmune hepatitis is a chronic disorder characterized by ongoing hepatocellular necrosis and inflammation, often progressing to fibrosis, cirrhosis, and liver failure. It is associated with hypergammaglobulinemia, autoantibodies, and histological findings of interface hepatitis.

Etiology

  • Idiopathic: The exact cause is unknown.
  • Immune Dysregulation: Triggered by environmental factors (e.g., infections, drugs) in genetically predisposed individuals.
  • Associated Conditions:Other autoimmune diseases (e.g., rheumatoid arthritis, thyroiditis, ulcerative colitis).
  • Genetics:Strong association with HLA-DR3 and HLA-DR4 alleles.

Epidemiology

    • Prevalence: Rare, affecting 1–2 per 100,000 people annually.
    • Gender: More common in females (3:1 ratio).
    • Age: Bimodal distribution: young adults (10–30 years) and middle-aged adults (40–60 years).
    • Regional Variation:
    • Type 1 AIH is the most common form in the United States.
    • Type 2 AIH is more common in Europe and presents at a younger age.

Classification

  • Type 1 AIH (“Classic AIH”):
  • Positive antinuclear antibody (ANA) and/or anti-smooth muscle antibody (ASMA) (specific to F-actin).
  • Associated with HLA-DRB1 03:01 (DR3) and HLA-DRB1 04:01 (DR4).
  • Commonly adult-onset.
  • Type 2 AIH:
  • Positive anti-liver-kidney microsomal type 1 (ALKM-1) and/or anti-liver cytosol antigen type 1 (ALC-1).
  • Associated with HLA-DRB1 07:01.
  • Typically childhood-onset.

Pathophysiology

       1.Autoimmune Activation:

  • Loss of immune tolerance leads to T-cell-mediated attack on hepatocytes.

       2.Cytokine Release:

  • Results in chronic inflammation and fibrosis.
  • Histological Features:
  • Interface hepatitis: Lymphoplasmacytic infiltration at the junction of the portal tract and liver parenchyma.

Histologic Findings

  • Gross Pathology:
  • Cirrhotic liver with fibrous septa and nodular appearance.
  • Microscopic Pathology:
  • Bridging fibrosis in the portal and periportal regions.
  • Hepatocyte necrosis.
  •  Plasma cell-rich lymphoplasmacytic infiltrate with interface hepatitis.

Clinical Manifestations

1.Asymptomatic (25–34%): Detected incidentally on abnormal liver function tests.

2.Symptomatic:

  • Acute Presentation: Jaundice, fatigue, nausea, right upper quadrant pain, and anorexia.
  • Chronic Presentation: Fatigue, malaise, mild hepatomegaly, progression to cirrhosis with portal hypertension (ascites, splenomegaly).

3.Extrahepatic Manifestations:

Arthralgia, skin rashes, thyroid dysfunction, or anemia.

Diagnosis

1.Laboratory Findings:

  • Elevated transaminases (ALT, AST).
  • Elevated IgG levels.
  • Positive autoantibodies:
  • Type 1: ANA, ASMA, anti-actin, anti-mitochondrial (PBC overlap), anti-SLA/LP, pANCA.
  • Type 2: ALKM-1, +/-ALC-1.

2.Liver Biopsy (Gold Standard):

  • Interface hepatitis: Dense lymphoplasmacytic infiltrate with plasma cells, hepatocyte necrosis, and bridging fibrosis.

3.Exclusion of Other Causes:

  • Viral hepatitis, drug-induced liver injury, and metabolic disorders.

Treatment

1.First-Line Therapy:

  • Corticosteroids (e.g., prednisone): To suppress inflammation.
  • Azathioprine: Steroid-sparing agent.

2.Alternative Immunosuppressants:

  • Mycophenolate mofetil, cyclosporine, or tacrolimus for refractory cases.

3.Liver Transplantation:

  • For end-stage liver disease or acute liver failure.

Prognosis

  • Good Prognosis: With early diagnosis and treatment, 10-year survival >80%.
  • Untreated Disease: Progresses to cirrhosis, liver failure, or hepatocellular carcinoma.
  • Relapse: Common after stopping treatment, requiring lifelong monitoring.

SUPERPoint

Autoimmune hepatitis is a chronic inflammatory liver disease characterized by autoantibodies and interface hepatitis, requiring immunosuppressive therapy to prevent progression to cirrhosis and liver failure.

 

SUPERFormula

Patient presents with right upper quadrant pain, jaundice + positive for anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal type 1 (ALKM-1) and/or anti-liver cytosol antigen type 1 (ALC-1) + hypergammaglobulinemia +  liver biopsy shows interface hepatitis with plasma cell predominance + Treated with corticosteroids and azathioprine + May progress to cirrhosis if untreated = Autoimmune Hepatitis (AIH).

 

References: 

Greene KG. Pathology of the Liver, Gallbladder, and Extrahepatic Biliary Tract. In: Reisner HM. eds. Pathology: A Modern Case Study, 2e. McGraw-Hill Education; 2020.

Li M, Zucker SD. Autoimmune Liver Disorders. In: Friedman S, Blumberg RS, Saltzman JR. eds. Greenberger’s CURRENT Diagnosis & Treatment Gastroenterology, Hepatology, & Endoscopy, 4e. McGraw Hill Education; 2022.