Gastroenterology · Hepatology
The facts most likely to be tested
Autoimmune hepatitis is characterized by elevated serum aminotransferases and hypergammaglobulinemia, specifically elevated IgG levels.
The most specific serologic marker for Type 1 autoimmune hepatitis is the presence of anti-smooth muscle antibodies (ASMA).
Type 1 autoimmune hepatitis is frequently associated with anti-nuclear antibodies (ANA) and occurs in a bimodal age distribution.
Type 2 autoimmune hepatitis is identified by the presence of anti-liver-kidney microsomal (anti-LKM-1) antibodies and is more common in pediatric patients.
Liver biopsy is the gold standard for diagnosis and typically reveals interface hepatitis with a lymphoplasmacytic infiltrate.
First-line treatment for autoimmune hepatitis is systemic corticosteroids (e.g., prednisone), often transitioned to azathioprine for long-term maintenance.
Autoimmune hepatitis is strongly associated with other autoimmune conditions such as Hashimoto thyroiditis, Graves disease, and Type 1 diabetes mellitus.
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A 28-year-old woman presents to the clinic with a 3-month history of fatigue, intermittent right upper quadrant discomfort, and dark urine. Physical examination reveals spider angiomata and mild hepatomegaly. Laboratory studies show an ALT of 450 U/L, AST of 380 U/L, and a markedly elevated serum IgG level. Serologic testing is positive for anti-smooth muscle antibodies (ASMA), while viral hepatitis panels are negative.
What is the most appropriate initial pharmacologic therapy for this patient?
Prednisone
The patient's presentation of elevated transaminases, hypergammaglobulinemia, and positive ASMA is diagnostic for Type 1 autoimmune hepatitis, which requires systemic corticosteroids as the first-line induction therapy.
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High yield triage
Etiology / Epidemiology
Predominantly affects young to middle-aged women with a bimodal distribution; associated with other autoimmune conditions.
Clinical Manifestations
Ranges from asymptomatic to acute liver failure; classic jaundice, hepatomegaly, and spider angiomata.
Diagnosis
Liver biopsy is the gold standard; look for elevated IgG and positive ASMA.
Treatment
Prednisone (with or without azathioprine) is first-line; avoid in patients with uncontrolled infection.
Prognosis
High risk of cirrhosis and hepatocellular carcinoma; requires lifelong monitoring.
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Epidemiology & Etiology
Strong female predilection (4:1 ratio) with peaks in adolescence and menopause. Frequently co-occurs with Hashimoto thyroiditis, Type 1 Diabetes, or Celiac disease. Genetic predisposition linked to HLA-DR3 and HLA-DR4 alleles.
Pertinent Anatomy
Inflammation targets the hepatocytes of the liver parenchyma. Chronic inflammation leads to periportal fibrosis and eventual architectural distortion of the liver lobules.
Pathophysiology
Loss of self-tolerance leads to T-cell mediated destruction of hepatocytes. Chronic immune activation results in interface hepatitis on histology. Persistent inflammation drives the progression from fibrosis to cirrhosis.
Clinical Manifestations
Patients often present with fatigue, malaise, and jaundice. Physical exam may reveal hepatomegaly, spider angiomata, and palmar erythema. Acute liver failure with encephalopathy or coagulopathy is a rare but life-threatening presentation.
Diagnosis
Diagnosis requires Liver biopsy showing interface hepatitis. Serology shows elevated IgG levels and positive ASMA (Anti-smooth muscle antibody) or ANA. Anti-LKM1 antibodies are specific for Type 2 disease.
Treatment
Induction therapy uses Prednisone (or budesonide in non-cirrhotics). Azathioprine is added for maintenance to allow for steroid tapering. Monitor for bone density loss and hyperglycemia during long-term steroid use.
Prognosis
Untreated disease leads to cirrhosis in 40% of patients. Regular screening for hepatocellular carcinoma via ultrasound is mandatory once cirrhosis is established.
Differential Diagnosis
Viral Hepatitis: positive serology for HAV, HBV, or HCV
Wilson Disease: low ceruloplasmin and Kayser-Fleischer rings
Primary Biliary Cholangitis: positive AMA and elevated alkaline phosphatase
Hemochromatosis: elevated ferritin and iron saturation
Drug-induced liver injury: temporal association with hepatotoxic medications