What is the recommended evaluation and management for an asymptomatic adult with incidentally discovered mild reactive transaminitis (elevated alanine aminotransferase and aspartate aminotransferase less than three times the upper limit of normal)?

Evaluation and Management of Asymptomatic Mild Reactive Transaminitis

Initial Assessment and Repeat Testing

For an asymptomatic adult with incidentally discovered mild transaminitis (ALT/AST <3× ULN), the first step is to repeat liver enzymes in 2–4 weeks to establish a trend, as many transient elevations resolve spontaneously without intervention. 1

• If enzymes normalize or decrease on repeat testing, no further immediate workup is needed; continue monitoring only if symptoms develop 1
• If ALT/AST remains <2× ULN but stable, monitor every 4–8 weeks until normalized or stabilized 1
• If ALT/AST increases to 2–3× ULN, repeat testing within 2–5 days and intensify evaluation 1

Comprehensive Initial Laboratory Workup

When transaminase elevation persists on repeat testing, obtain the following panel 1, 2:

Metabolic assessment:

• Fasting glucose or HbA1c and fasting lipid panel to assess for metabolic syndrome 1
• Waist circumference, blood pressure, and BMI measurement 1

Viral hepatitis serologies:

• Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc IgM), and hepatitis C antibody with reflex PCR 1, 2

Iron studies:

• Serum ferritin and transferrin saturation to screen for hereditary hemochromatosis; transferrin saturation >45% is clinically significant 1

Complete liver panel:

• AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time/INR to assess synthetic function and distinguish hepatocellular from cholestatic patterns 1, 3

Additional screening:

• Thyroid function tests (TSH) to exclude thyroid disorders as a cause 1
• Creatine kinase (CK) to rule out muscle disorders, particularly if AST is disproportionately elevated 1

Detailed Medication and Exposure History

Conduct a comprehensive medication review checking all prescription drugs, over-the-counter products, herbal supplements, and dietary supplements against the LiverTox® database, as medication-induced liver injury causes 8–11% of cases with mildly elevated transaminases. 1

• Quantify alcohol consumption using validated tools; intake ≥30 g/day in men or ≥20 g/day in women can produce enzyme elevations 1
• Document duration and cumulative dose of any potentially hepatotoxic medications 3

First-Line Imaging

Abdominal ultrasound is the recommended initial imaging modality, with 84.8% sensitivity and 93.6% specificity for detecting moderate-to-severe hepatic steatosis. 1

• Ultrasound also identifies biliary obstruction, focal liver lesions, portal hypertension features, and structural abnormalities 1
• Normal ultrasound does not exclude NAFLD, as it misses mild steatosis when <20–30% of hepatocytes are affected 1

Risk Stratification for Advanced Fibrosis

Calculate the FIB-4 score using age, ALT, AST, and platelet count to stratify risk for advanced fibrosis. 1

• FIB-4 <1.3 (or <2.0 if age >65 years): Low risk for advanced fibrosis with ≥90% negative predictive value; continue monitoring 1
• FIB-4 >2.67: High risk for advanced fibrosis; refer to hepatology 1

Management Based on Most Likely Etiology

For nonalcoholic fatty liver disease (most common cause):

• Target 7–10% body weight loss through caloric restriction 1
• Adopt a low-carbohydrate, low-fructose diet 1
• Prescribe 150–300 minutes/week of moderate-intensity aerobic exercise (≥3 days/week) plus resistance training ≥2 days/week 1
• Manage metabolic comorbidities: treat dyslipidemia with statins, optimize diabetes control with GLP-1 receptor agonists or SGLT2 inhibitors 1

For alcoholic liver disease:

• Recommend complete alcohol cessation 1
• Monitor transaminases every 2–4 weeks after cessation 1

For medication-induced liver injury:

• Discontinue suspected hepatotoxic medications when medically feasible 1
• Monitor ALT every 3–7 days after discontinuation; expect normalization within 2–8 weeks 1

Hepatology Referral Criteria

Refer to hepatology if any of the following occur 1:

• Transaminases remain elevated ≥6 months without identified cause
• ALT increases to >5× ULN (>235 IU/L for males, >125 IU/L for females)
• Evidence of synthetic dysfunction (elevated INR, low albumin, thrombocytopenia)
• FIB-4 score >2.67
• ALT increases to ≥3× baseline or ≥300 U/L (whichever comes first)

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 is lower (19–25 IU/L vs. 29–33 IU/L in men) 1
• Do not attribute ALT elevations ≥5× ULN to NAFLD alone; this warrants investigation for viral hepatitis, autoimmune hepatitis, or drug-induced 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
• Do not delay viral hepatitis screening even in obese patients with presumed NAFLD 1
• Normal ALT does not exclude significant liver disease; up to 50% of patients with NAFLD and 10% with advanced fibrosis may have normal ALT using conventional thresholds 1