Version May 2024
| 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 |
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