What workup is recommended for an obese patient with elevated liver enzymes, specifically AST and ALT, and a weight of 320 pounds?

Workup for Elevated Liver Enzymes in an Obese Patient

Begin with a comprehensive metabolic panel, hepatitis B and C screening, and calculate FIB-4 score to risk-stratify for advanced fibrosis, as this patient most likely has metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) given the obesity and elevated transaminases. 1, 2

Initial Laboratory Evaluation

The core diagnostic workup should include:

• Complete blood count with differential and platelets – essential for FIB-4 calculation and assessment of synthetic function 2
• Comprehensive metabolic panel – including albumin and INR to evaluate for synthetic dysfunction 2
• Hepatitis B surface antigen and hepatitis C antibody – to exclude viral hepatitis as alternative causes 2, 3
• Fasting lipid panel – commonly abnormal in MASLD and part of metabolic syndrome assessment 2
• Hemoglobin A1c or fasting glucose – to screen for diabetes, a major risk factor for progressive liver disease 1, 3

Additional Testing to Exclude Alternative Diagnoses

• Iron studies (serum ferritin and transferrin saturation) – to exclude hemochromatosis, though isolated elevated ferritin is common in MASLD and does not indicate iron overload 3
• Autoimmune markers (anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody) – to exclude autoimmune hepatitis and primary biliary cholangitis 3
• Thyroid function tests – hypothyroidism can contribute to MASLD 1

Imaging

• Abdominal ultrasound – to confirm hepatic steatosis, which is the most likely finding given obesity and this enzyme pattern (AST:ALT ratio <1) 1, 3

Fibrosis Risk Stratification

Calculate FIB-4 score immediately using the formula: [Age × AST] / [Platelet count × √ALT] 1, 3

Interpretation thresholds:

• FIB-4 <1.3 (if age <65 years) = Low risk of advanced fibrosis → manage in primary care with lifestyle intervention and reassess annually 1, 3
• FIB-4 1.3-2.67 = Indeterminate risk → proceed to vibration-controlled transient elastography (VCTE/FibroScan) or alternative non-invasive test 1
• FIB-4 >2.67 = High risk of advanced fibrosis → refer to hepatology 1, 3

If VCTE is performed for indeterminate FIB-4:

• <8.0 kPa = Low risk → intensified management of comorbidities, reassess FIB-4 every 1-3 years 1
• ≥8.0 kPa = Refer to hepatology for diagnostic workup and management plan 1

Management Based on Risk Stratification

For low-risk patients (FIB-4 <1.3):

• Target 7-10% total body weight reduction through caloric restriction (500-1000 kcal/day deficit) and moderate-intensity exercise, as this threshold improves hepatic inflammation and fibrosis 1, 3
• Repeat liver enzymes in 2-3 months to establish trend 3, 4
• Reassess FIB-4 annually 1

For indeterminate or high-risk patients:

• Consider proprietary plasma biomarker tests (e.g., Enhanced Liver Fibrosis [ELF] score) or magnetic resonance elastography (MRE) if available 1
• Refer to hepatology if FIB-4 >2.67, persistent elevation >2× upper limit of normal after 3 months despite lifestyle modifications, or VCTE ≥8.0 kPa 1, 3

Urgent Referral Criteria

Immediate hepatology referral is warranted if:

• ALT >8× upper limit of normal or >5× baseline 2, 4
• ALT >3× upper limit of normal with total bilirubin >2× upper limit of normal 4
• Evidence of synthetic dysfunction (elevated INR, low albumin) 2, 4

Common Pitfalls to Avoid

• Do not assume normal ALT excludes significant liver disease – up to 50% of patients with MASLD have normal transaminases, and normal ALT does not exclude NASH 1
• Do not withhold statins – statins are not contraindicated in MASLD and may actually be beneficial for cardiovascular risk reduction 1, 3, 4
• Do not assume spontaneous resolution – 84% of abnormal liver tests remain abnormal at 1 month, and 75% remain abnormal at 2 years 2, 4
• Adjust FIB-4 thresholds for age – for patients >65 years, use lower cut-off of 2.0 instead of 1.3 1