In an adult with mildly elevated aspartate aminotransferase (AST) of 56 U/L and alanine aminotransferase (ALT) of 66 U/L, what is the appropriate initial evaluation and management?

Evaluation and Management of Mildly Elevated Transaminases

Initial Assessment

For an adult with AST 56 U/L and ALT 66 U/L, begin with a systematic evaluation to identify the underlying cause, as these mild elevations (<5× upper limit of normal) most commonly indicate nonalcoholic fatty liver disease (NAFLD), medication-induced liver injury, or viral hepatitis. 1, 2

The pattern of ALT > AST (ratio <1) is characteristic of NAFLD and helps distinguish this from alcoholic liver disease, which typically shows AST:ALT ratio >2. 1, 3

Immediate Laboratory Work-Up

Order the following tests to establish the etiology:

• Complete liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time/INR to assess both hepatocellular injury pattern and synthetic function 1, 2

• Viral hepatitis serologies: HBsAg, anti-HBc IgM, and anti-HCV antibody to exclude chronic viral hepatitis, which commonly causes fluctuating transaminase elevations 1, 4

• Metabolic parameters: Fasting glucose or HbA1c, fasting lipid panel, and assessment of blood pressure and waist circumference to evaluate for metabolic syndrome components that drive NAFLD 1, 4

• Iron studies: Serum ferritin and transferrin saturation to screen for hereditary hemochromatosis 1, 4

• Creatine kinase: To exclude muscle injury as a source of AST elevation, particularly if the patient has engaged in recent intensive exercise 1, 5

• Thyroid function tests: To rule out thyroid disorders as a cause of transaminase elevations 1, 4

Risk Factors to Assess

Obtain a detailed history focusing on:

• Alcohol consumption: Use quantitative tools (AUDIT or AUDIT-C); intake ≥14-21 drinks/week in men or ≥7-14 drinks/week in women suggests alcoholic liver disease 1

• Medication review: Check all prescription drugs, over-the-counter products, and herbal supplements against the LiverTox® database, as medication-induced liver injury causes 8-11% of cases with mildly elevated enzymes 1, 4

• Metabolic syndrome features: Obesity (particularly central adiposity), diabetes, hypertension, and dyslipidemia are strong risk factors for NAFLD 1, 4

First-Line Imaging

Order abdominal ultrasound as the initial imaging test; it has 84.8% sensitivity and 93.6% specificity for detecting moderate to severe hepatic steatosis and can identify biliary obstruction, focal liver lesions, and signs of portal hypertension. 1, 2, 5

Risk Stratification for Advanced Fibrosis

Calculate the FIB-4 score using age, ALT, AST, and platelet count to determine the need for hepatology referral. 1, 2

• FIB-4 <1.3 (or <2.0 if age >65): Low risk for advanced fibrosis, negative predictive value ≥90% 1
• FIB-4 >2.67: High risk for advanced fibrosis; requires hepatology referral 1, 2

Monitoring Strategy

• Repeat liver enzymes in 2-4 weeks to establish the trend and confirm persistence of elevation 1, 2

• If values remain stable or improve and a benign cause (e.g., NAFLD) is identified, continue monitoring every 4-8 weeks until normalized 1

• Escalate monitoring frequency if ALT increases to ≥3× ULN or doubles from baseline 1

Management Based on Most Likely Etiology

For NAFLD (Most Common Cause)

• Target 7-10% body weight loss through caloric restriction as the primary therapeutic goal 1

• Adopt a low-carbohydrate, low-fructose diet to reduce hepatic fat accumulation 1

• Prescribe 150-300 minutes/week of moderate-intensity aerobic exercise (≥3 days/week) plus resistance training ≥2 days/week; both reduce liver fat independent of weight loss 1

• Manage metabolic comorbidities aggressively: Treat dyslipidemia with statins, optimize diabetes control with GLP-1 receptor agonists or SGLT2 inhibitors, and control blood pressure 1

For Medication-Induced Liver Injury

• Discontinue suspected hepatotoxic medications when possible and monitor liver enzymes every 3-7 days until declining; expect normalization within 2-8 weeks after drug discontinuation 1

For Viral Hepatitis

• Refer for specific management based on viral etiology if serologies are positive 1

Criteria for Hepatology Referral

Refer to hepatology if any of the following are present:

• ALT remains elevated for ≥6 months without identified cause 1, 2

• ALT increases to >5× ULN (>235 IU/L for males, >125 IU/L for females) 1, 2

• Bilirubin increases to >2× ULN 1, 2

• Evidence of synthetic dysfunction (elevated INR, low albumin, thrombocytopenia) 1, 2

• FIB-4 score >2.67 indicating high risk for advanced fibrosis 1, 2

Critical Pitfalls to Avoid

• Do not assume mild ALT elevation is benign without proper evaluation; even modest increases can reflect significant pathology, especially in women whose normal ALT range (19-25 IU/L) is lower than men (29-33 IU/L) 1, 2

• Do not overlook non-hepatic causes of elevated transaminases, such as intensive exercise, muscle injury, cardiac injury, hemolysis, and thyroid disorders, which can all elevate transaminases, particularly AST 1, 5, 6

• Do not forget to calculate the FIB-4 score; it is a simple, evidence-based tool that identifies patients needing urgent specialist assessment 1, 2

• Normal ALT does not exclude significant liver disease; up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds 1, 5