Summary
Autoimmune hepatitis (AIH) is a rare form of chronic hepatitis that predominantly affects women. Although the etiology is unclear, it is commonly associated with other autoimmune conditions (e.g., type 1 diabetes mellitus, celiac disease). Clinical presentation varies and patients may be asymptomatic or even show signs of acute liver failure. Diagnosis is established based on the detection of autoantibodies (especially anti-smooth muscle antibodies) and the histologic findings of liver biopsy. Treatment consists of immunosuppressive medications such as prednisone and azathioprine. The prognosis is favorable if patients are treated appropriately; without treatment, cirrhosis may develop.
Classification
- Type 1 AIH (80% of cases): characteristic autoantibodies include antinuclear antibodies (ANAs), anti-smooth muscle antibodies (ASMAs), anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP)
- Type 2 AIH: characteristic autoantibodies include anti-liver-kidney microsomal-1 antibodies (anti-LKM-1), anti-liver cytosol antibodies-1 (ALC-1)
Epidemiology
- Prevalence: 0.1–2/100,000 white adults in the US, even less so in other ethnicities [1]
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Bimodal distribution: 10–20 years and 40–60 years [2]
- Type 1 AIH: most common in adults
- Type 2 AIH: most common in children
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Sex: ♀ > ♂
- Type 1: (∼ 4:1) [3]
- Type 2: (∼ 10:1)
Epidemiological data refers to the US, unless otherwise specified.
Etiology
- Idiopathic [4]
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AIH is commonly associated with other autoimmune conditions
- Type 1 AIH: Hashimoto thyroiditis, Grave disease, ulcerative colitis, celiac disease, rheumatoid arthritis
- Type 2 AIH: Hashimoto thyroiditis, type 1 diabetes mellitus, vitiligo
Clinical features
AIH has an insidious onset in most patients and its presentation varies widely, ranging from asymptomatic disease to severe symptoms or even acute liver failure.
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Nonspecific symptoms
- Fatigue
- Upper abdominal pain
- Weight loss
- Signs of acute liver failure (∼ ⅓ of patients)
Diagnostics
-
Laboratory tests
- ↑↑ ALT and ↑ AST; , ↑ γGT, ↑ ALP
- Serum antibodies
- Type 1 AIH: ANA, ASMA, anti-SLA/LP, AMA
- Type 2 AIH: anti-LKM-1, ALC-1
- Serum protein electrophoresis: hypergammaglobulinemia (↑ IgG)
- Normochromic anemia, thrombocytopenia, mild leukopenia, ↑ erythrocyte sedimentation rate (ESR)
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Liver biopsy: Biopsy should be performed following the detection of AIH antibodies to confirm the diagnosis.
-
Histological findings:
- Lymphoplasmacytic interface hepatitis:ongoing inflammatory process with lymphocytic infiltration, bridging or multiacinar necrosis, and fibrotic changes
- Bile duct changes (e.g., cholangitis, ductal injury)
-
Histological findings:
Diagnosis is established based on positive autoantibodies (e.g., anti-smooth muscle antibodies) and histological findings suggestive of autoimmune hepatitis!
References:[4][5]
Differential diagnoses
- Viral hepatitis (e.g., hepatitis C)
- Primary sclerosing cholangitis
- Primary biliary cirrhosis
- Alcoholic liver disease
- Nonalcoholic steatohepatitis
- Drug-induced liver injury
- Drug-induced autoimmune-like hepatitis (DIAH)
- Hemochromatosis
The differential diagnoses listed here are not exhaustive.
Treatment
-
Immunosuppressive medications
-
Induction therapy
- First-line: prednisone with or without azathioprine
- Second-line: mycophenolate, cyclosporine, tacrolimus
- Maintenance therapy: low doses of azathioprine or prednisone
-
Induction therapy
-
Liver cirrhosis
- See “Treatment of cirrhosis”.
- Liver transplantation is indicated in cases of decompensated liver cirrhosis.
Prognosis
-
10-year survival rate with treatment: > 90% [6]
- Lifelong therapy is usually required.
- Increased risk of developing hepatocellular carcinoma (HCC): follow-ups are recommended
- Type 2 AIH is associated with more severe disease, worse response to corticosteroids, and more frequent relapses.
- Increased risk of liver cirrhosis if left untreated