What are the possible causes of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a 17‑year‑old male?

Causes of Elevated AST and ALT in a 17-Year-Old Male

In a 17-year-old male with elevated transaminases, the most common causes are nonalcoholic fatty liver disease (NAFLD), viral hepatitis, medication-induced liver injury, and vigorous exercise or muscle injury. 1

Initial Diagnostic Approach

The evaluation must begin with determining the pattern and severity of enzyme elevation, as this guides the differential diagnosis and urgency of workup. 1

Severity Classification

• Mild elevation: <5× upper limit of normal (ULN) — for males, ALT <145-165 IU/L 1
• Moderate elevation: 5-10× ULN 1
• Severe elevation: >10× ULN, requiring urgent hepatology referral 1

AST/ALT Ratio Interpretation

• AST:ALT ratio <1 (ALT higher than AST) is characteristic of NAFLD, viral hepatitis, or medication-induced liver injury 1, 2
• AST:ALT ratio ≥2 is highly suggestive of alcoholic liver disease, though less common in this age group 1
• Normal AST with rising ALT is highly specific for acute hepatocellular injury 2

Most Common Causes in Adolescents

1. Nonalcoholic Fatty Liver Disease (NAFLD)

NAFLD is the leading cause of elevated transaminases in adolescents, particularly those with obesity or metabolic syndrome components. 1

• Affects up to 70% of obese individuals 2
• Typically presents with AST:ALT ratio <1 1, 2
• Associated with obesity, diabetes, hypertension, and dyslipidemia 1
• Up to 50% of patients with simple steatosis may have completely normal liver enzymes 1

2. Viral Hepatitis

• Hepatitis B and C commonly cause fluctuating transaminase elevations 1
• Acute viral hepatitis (hepatitis A, B, or E) typically shows higher elevations (>400 IU/L) 1
• ALT elevation can be disproportionate to AST, particularly in early infection phases 2

3. Medication and Supplement-Induced Liver Injury

• Accounts for 8-11% of cases with elevated liver enzymes 1, 2
• Review all prescription medications, over-the-counter drugs, herbal supplements, and dietary supplements 1
• Check medications against the LiverTox® database for hepatotoxic potential 1
• Common culprits include acetaminophen, antibiotics, and bodybuilding supplements 1

4. Exercise-Induced Elevation

• Vigorous exercise or intensive weight training can cause acute AST and ALT elevations that may be mistaken for liver injury 1
• AST is less liver-specific and can be elevated from skeletal muscle injury 1, 3
• Check creatine kinase (CK) to exclude muscle injury as the source 1

5. Autoimmune Hepatitis

• Can present with gradual ALT increases in adolescents 1
• Typically shows higher elevations and elevated autoantibodies (ANA, anti-smooth muscle antibody) 1
• More common in young females but can occur in males 1

Essential Laboratory Workup

Initial Panel

• Complete liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, prothrombin time/INR 1
• Viral hepatitis serologies: HBsAg, anti-HBc IgM, anti-HCV with reflex PCR 1
• Metabolic parameters: Fasting glucose or HbA1c, fasting lipid panel 1
• Creatine kinase (CK): To exclude muscle injury as source of transaminase elevation 1, 2
• Complete blood count: If not performed within 12 months 1

Additional Testing Based on Initial Results

• Iron studies (ferritin, transferrin saturation) to screen for hereditary hemochromatosis 1
• Autoimmune markers (ANA, anti-smooth muscle antibody, quantitative IgG) if other causes excluded 1
• Ceruloplasmin level for Wilson disease in patients <40 years old 1
• Alpha-1 antitrypsin level if clinically indicated 1
• Thyroid function tests to rule out thyroid disorders 1

Risk Stratification for Advanced Fibrosis

Calculate the FIB-4 score using age, ALT, AST, and platelet count to determine need for hepatology referral. 1

• FIB-4 <1.3: Low risk for advanced fibrosis (negative predictive value ≥90%) 1
• FIB-4 >2.67: High risk for advanced fibrosis, warrants hepatology referral 1, 2

First-Line Imaging

Abdominal ultrasound is the recommended initial imaging test. 1, 2

• Sensitivity of 84.8% and specificity of 93.6% for detecting moderate-to-severe hepatic steatosis 1
• Can identify biliary obstruction, focal liver lesions, and portal hypertension features 1
• Should be performed if liver enzymes remain elevated after repeat testing 1

Monitoring Strategy

• Repeat liver enzymes in 2-4 weeks to establish trend and exclude transient elevation 1
• If ALT increases to ≥3× ULN, repeat testing within 2-5 days and intensify evaluation 1
• If values remain stable or improve, continue monitoring every 4-8 weeks until normalized 1

Criteria for Hepatology Referral

Immediate referral is indicated when: 1, 2

• ALT increases to >5× ULN (>235 IU/L for males) 1
• Bilirubin increases to >2× ULN 1
• Evidence of synthetic dysfunction (elevated INR, low albumin, thrombocytopenia) 1
• FIB-4 score >2.67 indicating high risk for advanced fibrosis 1
• ALT remains elevated for ≥6 months without identified cause 1, 2

Common Pitfalls to Avoid

• Do not assume mild ALT elevation is benign without proper evaluation; even modest increases can reflect significant pathology 1
• Do not overlook non-hepatic causes of elevated transaminases, particularly intensive exercise and muscle injury 1
• Do not forget to calculate the FIB-4 score, a simple tool that identifies patients needing urgent specialist assessment 1
• Do not rely on ALT magnitude alone to predict liver disease severity; normal ALT can coexist with advanced fibrosis 1
• Avoid repeating the same tests without further investigation unless there is strong suspicion of a transient cause 1
• Consider macro-AST in patients with isolated, persistently elevated AST and negative workup; confirm with polyethylene glycol (PEG) precipitation test 4

Age-Specific Considerations

• Wilson disease must be considered in patients <40 years old, especially with apparent autoimmune hepatitis that responds poorly to treatment 1
• Hereditary hemochromatosis screening is important in adolescents with unexplained transaminase elevations 1
• Timely referral to pediatric gastroenterology/hepatology is recommended to avoid missing progressive but treatable conditions 1