What is the diagnosis and management plan for a 32-year-old obese female with elevated liver enzymes, hepatomegaly with diffuse cytosis on liver ultrasound, and a BMI of 32?

Diagnosis: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

This 32-year-old obese female with BMI 32, elevated transaminases (AST 60, ALT 91), and hepatomegaly with diffuse steatosis on ultrasound has MASLD (formerly NAFLD), and requires immediate fibrosis risk stratification using FIB-4 score to determine management intensity and need for hepatology referral. 1, 2

Diagnostic Confirmation

Exclude Alternative Diagnoses First

• Quantify alcohol consumption using validated screening tools (AUDIT-C), as >20 g/day in women excludes MASLD diagnosis and suggests MetALD or alcohol-related liver disease 1
• Complete viral hepatitis screening: hepatitis B surface antigen and hepatitis C antibody with reflex PCR if positive 2, 3
• Autoimmune workup: anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, and serum immunoglobulins to exclude autoimmune hepatitis and primary biliary cholangitis 2, 4
• Iron studies: simultaneous serum ferritin and transferrin saturation to exclude hemochromatosis, though isolated elevated ferritin is common in MASLD and does not indicate iron overload 2
• Review medications for hepatotoxic agents that could cause drug-induced liver injury 3

Confirm MASLD Diagnosis

The diagnosis is established by: hepatic steatosis (confirmed by ultrasound showing diffuse steatosis) plus at least one cardiometabolic risk factor (obesity with BMI 32 qualifies), and absence of other causes of liver disease 1

Immediate Risk Stratification for Advanced Fibrosis

Calculate FIB-4 Score

FIB-4 = [Age × AST] / [Platelet count × √ALT] 2, 4

For this 32-year-old patient:

• FIB-4 = (32 × 60) / (Platelet count × √91)
• Need complete blood count to obtain platelet count for calculation 1, 2

Interpretation and Management Pathway

If FIB-4 <1.3 (Low Risk):

• Manage in primary care with lifestyle intervention 2, 4
• Repeat non-invasive fibrosis testing every 2-3 years 4
• Annual cardiovascular risk assessment and diabetes screening with HbA1c 4

If FIB-4 1.3-2.67 (Indeterminate Risk):

• Obtain transient elastography (FibroScan) or calculate NAFLD Fibrosis Score as second-tier test 1
• If liver stiffness measurement (LSM) <8.0 kPa, manage in primary care 1
• If LSM ≥8.0 kPa, refer to hepatology 1

If FIB-4 >2.67 (High Risk):

• Immediate referral to hepatology for consideration of liver biopsy and advanced fibrosis management 2, 4
• Screen for hepatocellular carcinoma with ultrasound every 6 months if cirrhosis confirmed 4
• Screen for esophageal varices if LSM >20 kPa or platelets <150,000/mm³ 4

Metabolic Comorbidity Assessment

Screen for Type 2 Diabetes

• Obtain fasting glucose and HbA1c immediately, as 70% of patients with type 2 diabetes have NAFLD and diabetes significantly increases fibrosis risk 1, 4
• If HbA1c 5.7-6.4% (prediabetes range), perform 75g oral glucose tolerance test 1

Cardiovascular Risk Assessment

• Complete lipid panel: check triglycerides, HDL cholesterol, and LDL cholesterol 3, 4
• Blood pressure measurement: hypertension is a metabolic risk factor that increases progression risk 1
• Calculate 10-year cardiovascular risk, as cardiovascular disease is the leading cause of death in MASLD patients, not liver disease 1, 5

Additional Metabolic Markers

• Measure waist circumference to assess visceral adiposity, which correlates with disease severity better than BMI alone 1
• Consider HOMA-IR (fasting glucose × fasting insulin / 22.5) to quantify insulin resistance, though validity is limited in overt diabetes 1

Primary Treatment: Intensive Lifestyle Modification

Weight Loss Target

Target 7-10% total body weight reduction, as this threshold improves hepatic inflammation and fibrosis histologically 1, 2

For this 184-pound patient, target weight loss is 13-18 pounds over 6-12 months 2

Dietary Intervention

• Mediterranean diet: daily vegetables, fresh fruit, unsweetened high-fiber cereals, nuts, fish or white meat, olive oil, with minimal simple sugars and red/processed meats 1
• Caloric restriction: 500-1000 kcal/day deficit below maintenance requirements 2
• Alcohol restriction: complete abstinence is recommended, as even low alcohol intake (9-20 g/day) doubles the risk of adverse liver outcomes in MASLD 1

Exercise Prescription

• Moderate-intensity aerobic exercise OR resistance training, as both effectively reduce liver fat independent of weight loss 2
• Target 150 minutes per week of moderate-intensity activity 1

Pharmacologic Considerations

Diabetes Management (If Present)

• Preferentially use GLP-1 receptor agonists (semaglutide, tirzepatide) if type 2 diabetes is diagnosed, as these improve liver histology and promote weight loss 1, 4
• Metformin does not improve liver histology but is acceptable for diabetes management 1

Cardiovascular Risk Reduction

• Statins are NOT contraindicated in MASLD and should be used for cardiovascular risk reduction per standard guidelines 2
• In fact, statins may provide hepatoprotective benefits 2

MASLD-Specific Therapy

• Resmetirom is FDA-approved for non-cirrhotic MASH with significant fibrosis (stage ≥F2), but requires liver biopsy confirmation of NASH and fibrosis stage 1
• Vitamin E (800 IU/day) may be considered in biopsy-proven NASH without diabetes or cirrhosis, though data are limited 1, 5
• Pioglitazone may improve histology in biopsy-proven NASH but causes weight gain 1, 6

Monitoring Plan

Short-Term Follow-Up

• Repeat liver enzymes in 2-3 months to establish trend after lifestyle intervention 2
• Reassess weight, waist circumference, and metabolic parameters at 3-month intervals 1

Long-Term Surveillance

• Repeat FIB-4 every 2-3 years if initial score is low-risk 4
• Annual diabetes screening with HbA1c if not diabetic 4
• Annual cardiovascular risk assessment 4

Referral Triggers

• Persistent ALT elevation >2× upper limit of normal after 3 months of lifestyle intervention 2
• FIB-4 >2.67 or indeterminate FIB-4 with LSM ≥8.0 kPa 2, 4
• Development of cirrhosis complications: ascites, variceal bleeding, hepatic encephalopathy 1

Critical Pitfalls to Avoid

• Do not delay fibrosis assessment: simple steatosis and NASH cannot be distinguished by imaging or liver enzymes alone, and 66% of physicians incorrectly believe NASH can be diagnosed with liver imaging 1
• Do not assume normal liver enzymes exclude advanced disease: up to 20% of patients with NASH have normal transaminases 1
• Do not withhold statins: 73% of physicians in one survey incorrectly considered statins contraindicated in fatty liver disease 1
• Do not recommend total alcohol abstinence without evidence-based rationale: while 42% of hepatologists recommend total abstinence, the threshold is >20 g/day in women for MASLD diagnosis 1