What is the appropriate evaluation and management for a patient with elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST) levels?

History and Physical Examination for Elevated ALT/AST

The initial evaluation should focus on identifying the most common causes: detailed alcohol consumption history (≥14-21 drinks/week in men or ≥7-14 drinks/week in women suggests alcoholic liver disease), comprehensive medication review including all prescription drugs, over-the-counter products, and herbal supplements checked against hepatotoxic potential, assessment for metabolic syndrome components (obesity, diabetes, hypertension), and risk factors for viral hepatitis. 1

Critical History Components

Alcohol and Substance Use

• Quantify alcohol intake precisely: Document drinks per week, as ≥14-21 drinks/week in men or ≥7-14 drinks/week in women indicates alcoholic liver disease risk 1
• Assess for other substance abuse including recreational drugs 2

Medication and Supplement Review

• Review ALL medications against the LiverTox® database for hepatotoxic potential, including prescription drugs, over-the-counter products, herbal supplements, and dietary supplements, as medication-induced liver injury causes 8-11% of cases with elevated transaminases 1
• Recent medication changes or new supplements in the past 6 months 1

Metabolic Risk Factors

• Measure waist circumference and blood pressure to assess for metabolic syndrome 1
• Screen for obesity, type 2 diabetes, hypertension, and dyslipidemia, as nonalcoholic fatty liver disease (NAFLD) is the most common cause of persistently elevated ALT, affecting up to 30% of the population 1, 3

Viral Hepatitis Risk Factors

• Document risk factors for hepatitis B and C: injection drug use history, blood transfusions before 1992, tattoos, high-risk sexual behavior, healthcare exposure, country of origin from endemic areas 1, 2
• Family history of viral hepatitis 2

Symptoms of Chronic Liver Disease

• Assess for fatigue, jaundice, pruritus, easy bruising, abdominal distension, confusion 1
• Right upper quadrant pain or discomfort 4

Family History

• Family history of liver disease, cirrhosis without alcohol abuse, hemochromatosis, Wilson disease, or autoimmune conditions 1, 5

Physical Examination Findings

Signs of Chronic Liver Disease

• Jaundice, scleral icterus 1
• Spider angiomata, palmar erythema 4
• Hepatomegaly or hepatic tenderness on palpation 4
• Splenomegaly suggesting portal hypertension 4
• Ascites, peripheral edema 4
• Asterixis indicating hepatic encephalopathy 4

Metabolic Syndrome Features

• Body mass index calculation and waist circumference measurement (central obesity is a key NAFLD risk factor) 1
• Blood pressure measurement (hypertension is part of metabolic syndrome) 1
• Acanthosis nigricans suggesting insulin resistance 1

Non-Hepatic Causes

• Thyroid examination (thyroid disorders can elevate transaminases) 1, 3
• Muscle tenderness or weakness (polymyositis, muscle injury can elevate AST more than ALT) 2, 3
• Cardiac examination (acute myocardial infarction can elevate AST) 5, 2

Initial Laboratory Testing

Complete Liver Panel

• AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, prothrombin time/INR to assess for cholestatic patterns and synthetic function 1
• Note that ALT is more liver-specific than AST, which can be elevated from cardiac muscle, skeletal muscle, kidney, or red blood cell disorders 1, 5

Viral Hepatitis Serologies

• HBsAg, hepatitis B core IgM, HCV antibody as part of initial evaluation 1

Metabolic Parameters

• Fasting lipid profile, glucose, hemoglobin A1c to assess for metabolic syndrome 1

Additional Screening Tests

• Serum iron, ferritin, total iron-binding capacity to screen for hemochromatosis 1, 3
• Thyroid function tests (TSH) to rule out thyroid disorders 1, 3
• Creatine kinase to exclude muscle injury as source of AST elevation, particularly if recent intensive exercise or muscle injury 1, 3

Common Pitfalls to Avoid

• Do not assume mild ALT elevation is benign without proper evaluation, as ALT elevation ≥5× upper limit of normal (ULN) is rare in NAFLD/NASH alone and requires investigation for viral hepatitis, autoimmune hepatitis, or drug-induced liver injury 1
• Do not overlook non-hepatic causes such as intensive exercise, muscle injury, cardiac injury, hemolysis, and thyroid disorders, which can elevate transaminases, particularly AST 1, 3
• Remember that normal ALT ranges differ by sex: 29-33 IU/L for males and 19-25 IU/L for females, significantly lower than commercial laboratory cutoffs 1
• AST/ALT ratio >2 is highly suggestive of alcoholic liver disease, with ratios >3 being particularly specific 1
• In chronic viral hepatitis, enzyme elevation may not correlate well with degree of liver damage, requiring additional assessment 2