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| Etiology | Clinical clues | Initial diagnostic testing |
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| Common causes |
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Drugs
(including prescribed, over the counter, illicit drug use and herbals) | (i) Lack of illness prior to taking the drug
(ii) Clinical illness or biochemical abnormalities developing after beginning the drug
(iii) Improvement after the drug is withdrawn | History |
| Alcohol abuse | Excessive alcohol consumption, AST/ALT ratio ≥ 2.0 | Accurate history, CAGE questionnaire, AST/ALT ratio, γ-glutamyl transpeptidase level (GGT) |
| Nonalcoholic fatty liver disease (NAFLD) | Evidence of metabolic syndrome (dyslipidemia, hypertension, diabetes or central obesity)
AST/ALT ratio < 1.0 | Fasting lipid profile, glucose level; consider ultrasonography to detect hepatic steatosis |
| Hepatitis B | High risk factors including (Immigration from endemic countries, high risk sexual behavior, and intravenous drug use) | Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (HBcAb) |
| Hepatitis C | Parenteral exposure (blood transfusions, intravenous drug use, occupational), tattoos, body piercing, and high risk sexual behavior | Hepatitis C virus antibody testing |
| Hereditary Hemochromatosis | Family history | Transferrin saturation and ferritin levels |
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| Less common causes |
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| Autoimmune hepatitis | Personal of family history of other autoimmune diseases | Immunoglobulin G levels, Serum protein electrophoresis (SPEP); antinuclear antibodies (ANA), smooth muscle antibodies (SMA) and liver-kidney microsomal antibodies testing (LKMA) |
| Wilson’s disease | Younger than 40 years, neuropsychiatric symptoms, Kayser-Fleischer rings | Serum ceruloplasmin level and ophthalmologist consultation to rule out Kayser-Fleischer rings |
| α1-antitrypsin deficiency | Early-onset emphysema, family history | Serum α1-antitrypsin level and SPEP |
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| Non-Hepatic causes |
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| Muscle disorders | Muscle weakness and pain, strenuous exercise | Creatine kinase (CK) and aldolase levels |
| Thyroid disorders | Signs and symptoms of hypo- or hyperthyroidism | Thyroid-stimulating hormone (TSH) level |
| Celiac disease | Diarrhea, abdominal pain, malabsorption | Tissue transglutaminase antibody (TTG) testing |
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