In a 30-year-old woman with chronic fatigue, markedly elevated AST and ALT, modestly elevated alkaline phosphatase and γ‑glutamyl transferase, splenomegaly, negative viral hepatitis and Wilson disease work‑up, which test best supports a diagnosis of autoimmune hepatitis?

Autoimmune Hepatitis Diagnosis

In this 30-year-old woman with markedly elevated transaminases, hypergammaglobulinemia, splenomegaly, and negative viral/Wilson workup, the test that best supports autoimmune hepatitis diagnosis is increased IgG immunoglobulins and gamma globulins (option c), as elevated IgG and hypergammaglobulinemia are diagnostic hallmarks of autoimmune hepatitis. 1

Diagnostic Reasoning

Why IgG and Gamma Globulins Are Most Supportive

• Elevated serum gamma-globulin or IgG levels >1.5 times the upper normal limit are central diagnostic criteria for autoimmune hepatitis, appearing in approximately 85% of patients even without cirrhosis 1
• The simplified diagnostic scoring system specifically awards 2 points for IgG >upper normal limit, making this a weighted diagnostic feature 1
• Hypergammaglobulinemia is one of the three diagnostic hallmarks of autoimmune hepatitis (along with autoantibodies and interface hepatitis on histology) 2

Why Other Options Are Less Definitive

ANA and SMA (option a):

• While ANA and SMA are important, they are present in only 96% of North American adults with autoimmune hepatitis, and 4% of patients lack these conventional antibodies entirely 1
• In acute presentations of autoimmune hepatitis, ANA may be absent or weakly demonstrated in 29-39% of patients 1
• These antibodies support but do not confirm the diagnosis without other features 1

IgM immunoglobulins (option b):

• Elevated IgM is characteristic of primary biliary cholangitis, not autoimmune hepatitis 1
• This patient's hepatocellular pattern (AST 5x, ALT 10x) with only modest alkaline phosphatase elevation (1.3x) argues against a cholestatic disease 1

Liver biopsy (option d):

• While histology showing interface hepatitis is essential for diagnosis, the question asks which test "supports" the diagnosis, and biopsy confirms rather than supports 1
• Pre-treatment liver biopsy is recommended when possible, but the serologic findings (elevated IgG) point toward the diagnosis before biopsy 1

Magnetic cholangiography (option e):

• MRCP is indicated when primary sclerosing cholangitis is suspected, particularly in children with autoimmune hepatitis-like features 1
• This patient's predominantly hepatocellular pattern makes cholangiopathy unlikely 1

Clinical Context and Pitfalls

Important Diagnostic Considerations

• This patient's presentation is classic for autoimmune hepatitis: young woman, marked transaminase elevation (ALT 10x > AST 5x), modest cholestatic enzyme elevation, splenomegaly from portal hypertension, and negative viral/Wilson testing 1, 3
• The splenomegaly (10 cm longitudinal diameter) suggests underlying cirrhosis or advanced fibrosis, as approximately one-third of adults with autoimmune hepatitis have cirrhosis at presentation 1

Critical Exclusions Already Completed

• Wilson disease was appropriately excluded, which is crucial since it can present identically to autoimmune hepatitis in young patients 1, 4
• All pediatric patients and adults with atypical autoimmune hepatitis must be screened for Wilson disease before diagnosis 1, 4
• Viral hepatitis markers are negative, excluding hepatitis B and C 1

Diagnostic Algorithm

The complete diagnostic workup should include:

• Serum IgG and gamma-globulin levels (already pointing to diagnosis) 1
• Conventional autoantibodies (ANA, SMA, anti-LKM1, anti-LC1) at titers >1:40 in adults 1
• Liver biopsy showing interface hepatitis with plasma cell infiltration 1, 2
• Exclusion of other causes: viral hepatitis, Wilson disease (done), alpha-1 antitrypsin deficiency, drug-induced liver injury 1

Common Pitfalls to Avoid

• Do not delay diagnosis waiting for positive autoantibodies—some patients with autoimmune hepatitis have negative conventional antibodies but elevated IgG 1
• In acute presentations, IgG may be normal in 25-39% of patients, making diagnosis more challenging 1
• **The AST:ALT ratio <1 helps distinguish this from alcoholic liver disease** (where ratio is typically >2), though patient denies alcohol use 1
• Splenomegaly in a young patient with hepatitis should prompt consideration of cirrhosis with portal hypertension, not just acute inflammation 1, 5