Step 1: Initial evaluation |
Review possible links to medications, herbal therapies, or recreational drugs |
Screen for alcohol abuse (history, screening instruments, AST/ALT ratio >2:1) |
Obtain serology for hepatitis B and C (HBsAg, anti-HBs, anti-HBc, anti-HCV) |
Screen for hemochromatosis (Fe/TIBC >45%) |
Evaluate for fatty liver (AST/ALT usually <1, obtain RUQ ultrasonography) |
Step 2: Second-line evaluation (if initial evaluation is unrevealing) |
Consider autoimmune hepatitis, particularly in women and in those with a history of other autoimmune disorders (check serum protein electrophoresis; obtain ANA and ASMA if positive) |
Obtain thyroid function tests (TSH if hypothyroidism is suspected; otherwise, obtain serum TSH, free T4, and T3 concentrations) |
Consider celiac disease (especially in patients with a history of diarrhea or unexplained iron deficiency: serum IgA anti-tissue transglutaminase antibodies) |
Step 3: Evaluation for uncommon causes (if second-line evaluation is unrevealing) |
Consider Wilson disease, especially in those <40 years of age (check serum ceruloplasmin, evaluate for Kayser-Fleischer rings) |
Consider alpha-1 antitrypsin deficiency, especially in patients with a history of emphysema out of proportion to their age or smoking history (obtain alpha-1 antitrypsin level) |
Consider adrenal insufficiency (8 am serum cortisol and plasma ACTH, high-dose ACTH stimulation test) |
Exclude muscle disorders (obtain creatine kinase or aldolase) |
Step 4: Obtain a liver biopsy or observe (if no source identified after steps 1 to 3) |
Observe if ALT and AST are less than twofold elevated |
Otherwise, consider a liver biopsy |