What is the clinical significance of an alanine aminotransferase level of 90 U/L and an aspartate aminotransferase level of 115 U/L?

Clinical Significance of ALT 90 and AST 115

These values represent mild hepatocellular injury (approximately 2-3× the upper limit of normal) that warrants systematic evaluation but does not require urgent intervention. 1

Severity Classification

• Using sex-specific reference ranges (ALT: 29-33 IU/L for males, 19-25 IU/L for females; AST: 32 IU/L for males, 26 IU/L for females), these elevations fall into the mild category (<5× ULN). 1, 2
• For males: ALT 90 represents ~3× ULN and AST 115 represents ~3.6× ULN. 1
• For females: ALT 90 represents ~3.6-4.7× ULN and AST 115 represents ~4.4× ULN. 1, 2
• The AST/ALT ratio of 1.28 (AST > ALT) is noteworthy, as most non-alcoholic liver diseases present with ALT > AST. 1

Clinical Significance of the Enzyme Pattern

• The AST/ALT ratio >1 suggests several possibilities:

  • Alcoholic liver disease (AST/ALT ratio >2 is highly suggestive, with ratios >3 being particularly specific). 1
  • Advanced fibrosis or cirrhosis from any cause (the ratio reverses as fibrosis progresses). 1
  • Less likely: Wilson disease in acute presentation, though this typically shows much higher AST elevations. 1

• AST is less liver-specific than ALT and can be elevated from cardiac muscle injury, skeletal muscle injury (including recent vigorous exercise), kidney disorders, or hemolysis. 1, 3

Immediate Diagnostic Approach

Complete the following evaluation within 2-4 weeks: 1

Essential Laboratory Testing

• Complete liver panel: Total and direct bilirubin, alkaline phosphatase, GGT, albumin, prothrombin time/INR to assess synthetic function and distinguish hepatocellular from cholestatic patterns. 1
• Viral hepatitis serologies: HBsAg, anti-HBc IgM, anti-HCV to identify viral causes. 1
• Metabolic parameters: Fasting glucose or HbA1c, fasting lipid panel to assess for metabolic syndrome components. 1
• Creatine kinase (CK): Essential to exclude muscle injury as the source of AST elevation, particularly if recent exercise or muscle trauma occurred. 1

Critical History Elements

• Detailed alcohol consumption: Quantify drinks per week (≥14-21 drinks/week in men or ≥7-14 drinks/week in women suggests alcoholic liver disease). 1
• Complete medication review: Check all prescription drugs, over-the-counter medications, herbal supplements, and dietary supplements against the LiverTox® database, as medication-induced liver injury causes 8-11% of cases. 1
• Metabolic risk factors: Assess for obesity (measure waist circumference), diabetes, hypertension, and dyslipidemia as NAFLD risk factors. 1

First-Line Imaging

• Abdominal ultrasound is recommended as the initial imaging modality with 84.8% sensitivity and 93.6% specificity for detecting moderate-to-severe hepatic steatosis. 1
• Ultrasound can identify biliary obstruction, focal liver lesions, and portal hypertension features. 1

Risk Stratification for Advanced Fibrosis

Calculate the FIB-4 score using age, ALT, AST, and platelet count: 1

• FIB-4 <1.3 (<2.0 if age >65): Low risk for advanced fibrosis (negative predictive value ≥90%). 1
• FIB-4 >2.67: High risk for advanced fibrosis requiring hepatology referral. 1

Management Based on Most Likely Causes

If Alcoholic Liver Disease is Suspected (AST/ALT >1)

• Immediate alcohol cessation is strongly recommended, as even moderate consumption impedes liver recovery. 1
• Repeat liver enzymes within 2-5 days if AST/ALT ratio ≥2 with clinical concern for alcoholic hepatitis. 1

If NAFLD is Suspected (with metabolic risk factors)

• Lifestyle modifications are the cornerstone: Target 7-10% weight loss through caloric restriction, low-carbohydrate/low-fructose diet, and 150-300 minutes of moderate-intensity aerobic exercise weekly. 1
• Aggressively treat metabolic comorbidities: statins for dyslipidemia, GLP-1 receptor agonists or SGLT2 inhibitors for diabetes. 1

If Medication-Induced Liver Injury is Suspected

• Discontinue suspected hepatotoxic medications when possible. 1
• Expect normalization within 2-8 weeks after drug discontinuation if medication-induced. 1

Monitoring Protocol

• Repeat liver enzymes in 2-4 weeks to establish the trend. 1
• If values normalize or decrease: Continue monitoring every 4-8 weeks until stabilized. 1
• If ALT/AST increases to ≥3× baseline or reaches ≥300 U/L: Perform abdominal ultrasound and intensify evaluation for alternative etiologies. 1
• If ALT increases to >5× ULN (>145-165 IU/L for males, >125 IU/L for females) or bilirubin >2× ULN: Urgent hepatology referral is warranted. 1

Hepatology Referral Criteria

Refer to hepatology if: 1

• Liver enzymes remain elevated for ≥6 months without identified cause
• ALT increases to >5× ULN
• Evidence of synthetic dysfunction (low albumin, elevated INR)
• FIB-4 score >2.67 indicating high risk for advanced fibrosis

Critical Pitfalls to Avoid

• Do not assume these elevations are benign without proper evaluation, as ALT elevation ≥5× ULN is rare in simple NAFLD and usually indicates viral hepatitis, autoimmune hepatitis, or drug-induced liver injury. 1
• Do not overlook non-hepatic causes of AST elevation, particularly recent intensive exercise, muscle injury, or cardiac injury. 1
• Do not ignore the AST/ALT ratio >1, as this pattern warrants specific investigation for alcohol use and assessment for advanced fibrosis. 1
• Remember that normal ALT does not exclude significant liver disease—up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds. 1