What is the workup and treatment for a patient with a CT scan showing diffuse hepatic steatosis?

Workup and Treatment of Diffuse Hepatic Steatosis on CT Scan

Begin with risk stratification using FIB-4 score to determine fibrosis risk, then implement lifestyle modifications as first-line therapy for all patients, reserving pharmacotherapy only for those with confirmed steatohepatitis and significant fibrosis (≥F2). 1, 2

Initial Diagnostic Workup

Confirm the Diagnosis and Assess Cardiometabolic Risk

• Verify the presence of at least one cardiometabolic risk factor (obesity, type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome) to classify this as metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD). 1
• Obtain detailed alcohol history: consumption must be <30 g/day in men and <20 g/day in women to confirm MASLD rather than alcohol-related liver disease. 1
• Exclude secondary causes: review medications (corticosteroids, amiodarone, methotrexate, tamoxifen, valproic acid), screen for hepatitis B/C, and consider rare causes (Wilson disease, autoimmune hepatitis, α1-antitrypsin deficiency, hemochromatosis). 1, 3

Laboratory Assessment

• Baseline liver evaluation: complete blood count, comprehensive metabolic panel including ALT/AST/GGT, international normalized ratio, fasting glucose, HbA1c, lipid panel, and creatinine. 1, 4
• Diabetes screening is mandatory: perform fasting glucose, HbA1c, and consider 75g oral glucose tolerance test in high-risk individuals (HbA1c 5.7-6.4% or fasting glucose 100-125 mg/dL). 1
• Extended workup if indicated: ferritin with transferrin saturation, thyroid function tests, tests for celiac disease. 1

Risk Stratification for Fibrosis

Calculate FIB-4 score as the first-tier non-invasive assessment to stratify patients: 1, 4

• Low risk: FIB-4 <1.3 → manage in primary care with lifestyle interventions and annual follow-up
• Intermediate risk: FIB-4 1.3-2.67 → proceed to transient elastography (FibroScan)
• High risk: FIB-4 >2.67 → refer to hepatology for transient elastography and possible liver biopsy

If transient elastography is performed: 1

• Liver stiffness measurement (LSM) <8.0 kPa confirms low risk
• LSM 8.0-12.0 kPa indicates intermediate risk
• LSM >12.0 kPa or ≥20 kPa (cirrhosis range) requires hepatology referral

Treatment Approach

Lifestyle Modifications (All Patients)

Weight Loss Targets (progressive, not exceeding 1 kg/week to avoid worsening liver disease): 1, 2, 4

• 3-5% weight loss improves steatosis
• 5-7% weight loss reduces intrahepatic fat and inflammation
• 7-10% weight loss improves steatohepatitis and potentially reverses fibrosis
• Implement hypocaloric diet with 500-1000 kcal daily deficit 4

Dietary Pattern: 2, 3, 4

• Adopt Mediterranean diet: vegetables, fruits, fiber-rich cereals, nuts, fish or white meat, olive oil as primary fat source 5
• Avoid: fructose-containing beverages, sugar-sweetened drinks, ultra-processed foods high in saturated fat 3, 4
• The Mediterranean diet reduces liver steatosis by 39% compared to 7% with low-fat/high-carbohydrate diet, even without significant weight loss 5

Physical Activity: 2, 3, 4

• Prescribe 150-300 minutes/week of moderate-intensity exercise OR 75-150 minutes/week of vigorous-intensity exercise
• Exercise reduces steatosis and improves liver enzymes even without significant weight loss 2

Alcohol Consumption: 1, 4

• Discourage heavy alcohol consumption in all MASLD patients
• Consider limiting intake below 30g/day for men and 20g/day for women, or advise complete abstinence 4

Management of Cardiometabolic Comorbidities

Type 2 Diabetes: 2, 3, 4

• First-line: GLP-1 receptor agonists (semaglutide, liraglutide) improve both glycemic control and liver histology
• Alternative: SGLT2 inhibitors (empagliflozin, dapagliflozin) are beneficial
• Avoid sulfonylureas and minimize insulin use when possible 4

Dyslipidemia: 2, 3, 4

• Statins are safe and recommended for all MASLD patients with dyslipidemia
• Statins reduce HCC risk by 37% in meta-analyses 2

Hypertension and Other Risk Factors: 3, 4

• Optimize blood pressure control and manage all components of metabolic syndrome

Pharmacologic Treatment for Advanced Disease

Pharmacotherapy is reserved ONLY for patients with: 1, 2

• Biopsy-proven steatohepatitis (MASH/NASH) AND
• Significant fibrosis (stage ≥F2)

Treatment Options for Eligible Patients: 1

• Resmetirom (if locally approved): for non-cirrhotic MASH with significant fibrosis (>F2), demonstrated histological effectiveness on steatohepatitis and fibrosis 1
• Vitamin E (800 IU/day): consider in select patients with biopsy-proven NASH, preferably in randomized controlled trials 1, 2
• Pioglitazone: may be considered in biopsy-proven NASH 1
• High-dose ursodeoxycholic acid: possibly associated with vitamin E or pioglitazone 1

Do NOT use pharmacotherapy for: 2, 4

• Simple steatosis without inflammation
• Low-risk patients (FIB-4 <1.3, LSM <8.0 kPa, F0-F1 fibrosis)
• Cirrhotic stage (no MASH-targeted pharmacotherapy currently recommended) 1

Special Considerations

Bariatric Surgery: 1, 3, 4

• Consider in appropriate individuals with clinically significant fibrosis and obesity with comorbidities
• Valid option for obese patients with MASLD/MASH if otherwise indicated 1

Cirrhosis Management: 1, 2

• HCC surveillance is mandatory (ultrasound ± AFP every 6 months)
• Screen for gastroesophageal varices if LSM ≥20 kPa or thrombocytopenia present 2
• Nutritional counseling and surveillance for portal hypertension 1
• Liver transplantation for decompensated cirrhosis 1

Follow-Up Strategy

Low-Risk Patients (FIB-4 <1.3, LSM <8.0 kPa): 2, 4

• Annual follow-up with repeated non-invasive tests
• Repeat liver function tests and FIB-4 in 6-12 months

Intermediate/High-Risk Patients: 2, 4

• Refer to hepatology for specialized management
• More frequent monitoring (every 3-6 months)
• Consider liver biopsy for definitive diagnosis and staging 1

Common Pitfalls to Avoid

• Do not prescribe metformin specifically for liver disease in MASLD—it has no significant effect on liver histology 4
• Avoid rapid weight loss (>1 kg/week)—this may worsen liver disease; gradual weight loss is essential 1, 4
• Do not withhold statins due to concerns about liver toxicity—they are safe and beneficial in MASLD 2, 3
• Do not use pharmacotherapy for simple steatosis—reserve it only for biopsy-proven NASH with significant fibrosis 1, 2, 4
• CT has limitations in evaluating hepatic steatosis in patients with infiltrative liver diseases that deposit iron, copper, glycogen, or amiodarone 4