What is the appropriate work‑up for a patient with elevated alanine aminotransferase (~90 U/L) and aspartate aminotransferase (~115 U/L)?

Work-up for ALT 90 and AST 115

Begin with a complete liver panel, detailed medication review, alcohol history, and abdominal ultrasound to identify the most common causes: nonalcoholic fatty liver disease, medication-induced injury, alcohol-related disease, or biliary obstruction. 1

Initial Laboratory Testing

Complete the following blood work immediately:

• Complete liver panel: Include alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time/INR to assess for cholestatic patterns and synthetic function 1
• Viral hepatitis serologies: HBsAg, anti-HBc IgM, and HCV antibody to rule out viral causes 1
• Metabolic parameters: Fasting glucose or HbA1c and fasting lipid panel, as metabolic syndrome is a major risk factor for NAFLD 1
• Creatine kinase: To exclude muscle injury as a source of AST elevation, particularly if recent vigorous exercise occurred 1
• Thyroid function tests: TSH to rule out thyroid disorders as a cause of transaminase elevations 1

The AST/ALT ratio of approximately 1.3 (115/90) suggests either early alcoholic liver disease or advanced fibrosis, though ratios >2 are more specific for alcohol-related disease 1. This mild elevation (approximately 2-3× upper limit of normal for sex-specific ranges) represents Grade 1-2 hepatocellular injury 1.

Critical History Elements

Obtain specific details about:

• Alcohol consumption: Quantify as drinks per week (≥14-21 drinks/week in men or ≥7-14 drinks/week in women suggests alcoholic liver disease) 1
• All medications: Check prescription drugs, over-the-counter products, herbal supplements, and dietary supplements against the LiverTox® database, as medication-induced injury causes 8-11% of cases 1
• Metabolic risk factors: Measure waist circumference, blood pressure, and assess for obesity, diabetes, hypertension, and dyslipidemia as NAFLD risk factors 1
• Symptoms of chronic liver disease: Fatigue, jaundice, pruritus, right upper quadrant pain 1

First-Line Imaging

Order abdominal ultrasound as the initial imaging study with sensitivity of 84.8% and specificity of 93.6% for detecting moderate to severe hepatic steatosis 1. This will identify:

• Hepatic steatosis (most common cause) 1
• Biliary obstruction or dilation 1
• Focal liver lesions 1
• Portal hypertension features 1

Critical pitfall: Choledocholithiasis can present with marked transaminase elevation mimicking hepatocellular injury rather than the expected cholestatic pattern, with approximately one-third of patients showing ALT or AST >500 IU/L 2. Severe abdominal pain with elevated liver enzymes strongly suggests biliary disease 3, 4.

Risk Stratification for Fibrosis

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

• Score <1.3 (<2.0 if age >65): Low risk for advanced fibrosis, negative predictive value ≥90% 1
• Score >2.67: High risk for advanced fibrosis, requires hepatology referral 1

Monitoring and Follow-up

Repeat liver enzymes in 2-4 weeks to establish trend and direction of change 1:

• If normalizing or decreasing: Continue monitoring every 4-8 weeks until stabilized 1
• If increasing to ≥3× ULN or doubling from baseline: Escalate monitoring and intensify evaluation 1
• If increasing to >5× ULN (>235 IU/L for males, >125 IU/L for females): Urgent hepatology referral 1

Management Based on Likely Etiology

For suspected NAFLD (most common cause with metabolic risk factors and AST:ALT <1):

• Target 7-10% weight loss through caloric restriction 1
• Low-carbohydrate, low-fructose diet 1
• 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

For medication-induced liver injury:

• Discontinue suspected hepatotoxic medications when possible 1
• Expect normalization within 2-8 weeks after drug discontinuation 1
• Monitor ALT every 3-7 days until declining 1

For alcoholic liver disease (if AST/ALT ratio >2):

• Recommend complete alcohol cessation 1
• Monitor transaminases for improvement 1

Hepatology Referral Criteria

Refer to hepatology if:

• Transaminases remain elevated ≥6 months without identified cause 1
• ALT increases to >5× ULN 1
• Evidence of synthetic dysfunction (low albumin, elevated INR) 1
• FIB-4 score >2.67 1

Common Pitfalls to Avoid

• Do not assume NAFLD without proper evaluation: ALT elevation ≥5× ULN is rare in NAFLD and requires investigation for viral hepatitis, autoimmune hepatitis, or drug-induced injury 1
• Do not overlook biliary obstruction: Choledocholithiasis can cause severe transaminase elevation (>1000 IU/L in 7.8% of cases) mimicking acute hepatitis 2, 5
• Do not ignore non-hepatic causes: AST can be elevated from cardiac, skeletal muscle, kidney, and red blood cell disorders 1
• Do not use commercial laboratory "normal" ranges: Sex-specific normal ALT is 29-33 IU/L for males and 19-25 IU/L for females, significantly lower than standard cutoffs 1, 6