What is the diagnosis and management for an adult non-drinker with elevated liver enzymes and hepatomegaly?

Diagnosis and Management of Elevated Liver Enzymes with Hepatomegaly in a Non-Drinker

This patient most likely has metabolic dysfunction-associated steatotic liver disease (MASLD), given the markedly elevated GGT (509), mild transaminase elevation with AST>ALT ratio of 1.3, hepatomegaly, and absence of alcohol use. 1

Immediate Diagnostic Workup

The pattern of liver enzyme elevation is critical for diagnosis:

• The predominant GGT elevation (509) with mild transaminase elevation (ALT 67, AST 89) suggests either MASLD or infiltrative liver disease 2
• The AST/ALT ratio of 1.3 is below the threshold of >1.5 typically seen in alcoholic liver disease, making alcohol-related disease less likely despite the elevated ratio 1
• Perform a comprehensive liver etiology screen immediately including: viral hepatitis B and C serologies, autoimmune markers (ANA, ASMA, immunoglobulins), iron studies (ferritin, transferrin saturation), and fasting metabolic panel 3, 4

Risk Stratification for Fibrosis

Calculate the FIB-4 score immediately using age, ALT, AST, and platelet count to assess risk of advanced fibrosis 3:

• FIB-4 >2.67 indicates high risk of advanced fibrosis and requires urgent hepatology referral 3
• If FIB-4 is intermediate (1.3-2.67), proceed with second-line testing such as Enhanced Liver Fibrosis (ELF) test or transient elastography (FibroScan) 3
• The hepatomegaly (19.2 cm) combined with elevated enzymes increases concern for significant fibrosis 1

Specific Diagnostic Considerations

Metabolic Syndrome Assessment

• Screen for components of metabolic syndrome: measure fasting glucose/HbA1c, lipid panel, blood pressure, and calculate BMI 1
• Type 2 diabetes and obesity are the strongest risk factors for MASLD progression to cirrhosis and hepatocellular carcinoma 1
• Males aged >50 years and individuals with multiple cardiometabolic risk factors are at increased risk of progressive fibrosis 1

Exclude Other Causes

• Check ferritin level: if >1000 µg/L in the absence of other risk factors, consider liver biopsy to exclude hemochromatosis and assess for cirrhosis 1
• Verify alcohol intake using AUDIT-C screening tool, as self-reported alcohol history may be unreliable 3
• Consider drug-induced liver injury by reviewing all medications, supplements, and herbal products 5

Imaging Studies

• Ultrasound or MRI should be performed to assess for steatosis, exclude biliary obstruction, and evaluate for cirrhotic features (nodular surface, splenomegaly, varices) 1
• Gradient dual-echo MRI can distinguish MASLD from glycogenic hepatopathy if diabetes is present 6

Management Strategy

If MASLD is Confirmed:

• Address all modifiable cardiometabolic risk factors through lifestyle modifications: weight loss of 7-10% if overweight, Mediterranean diet, and regular exercise 1
• Statins are not contraindicated in MASLD and should be used for cardiovascular risk reduction if indicated 4
• Monitor liver enzymes every 3-6 months initially 3

Referral Criteria to Hepatology:

Refer urgently if any of the following are present 3, 4:

• FIB-4 score >2.67 or other evidence of advanced fibrosis
• Liver enzymes remain >2× upper limit of normal after 3 months despite addressing modifiable factors
• Extended liver etiology screen is negative and no clear risk factors for MASLD are identified
• Evidence of synthetic dysfunction (prolonged INR, hypoalbuminemia) or portal hypertension

Critical Pitfalls to Avoid

• Do not assume normal aminotransferases exclude significant liver disease: patients with MASLD and normal ALT can still have significant steatohepatitis and develop advanced fibrosis 1
• The markedly elevated GGT (509) should not be dismissed as it indicates significant hepatocellular stress 2
• Liver biopsy may be necessary if the diagnosis remains unclear after comprehensive workup, particularly if ferritin is >1000 µg/L or if fibrosis assessment suggests advanced disease 1, 3
• Do not delay fibrosis assessment: 10-30% of patients with isolated steatosis progress to steatohepatitis and advanced liver disease, with much higher risk (42-65%) if diabetes is present 1