What is the appropriate workup and treatment for a patient presenting with hepatic steatosis?

Workup of Hepatic Steatosis

Begin by confirming the diagnosis meets criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) by documenting at least one cardiometabolic risk factor (obesity, dysglycemia, hypertension, or dyslipidemia), then immediately risk-stratify for clinically significant fibrosis using FIB-4 score as this determines all subsequent management decisions. 1, 2

Initial Diagnostic Assessment

Confirm MASLD Diagnosis

• Document cardiometabolic risk factors: BMI >25 kg/m² (>23 kg/m² in Asians), waist circumference >94 cm (men) or >80 cm (women), prediabetes/diabetes (HbA1c ≥5.7% or fasting glucose ≥100 mg/dL), triglycerides >150 mg/dL, HDL <40 mg/dL (men) or <50 mg/dL (women), or blood pressure >130/85 mmHg 1
• Obtain detailed alcohol history: consumption must be <30 g/day in men and <20 g/day in women to classify as MASLD rather than alcohol-related liver disease 1, 2

Exclude Secondary Causes

• Screen for viral hepatitis: hepatitis B surface antigen and hepatitis C antibody 2
• Review medications: corticosteroids, amiodarone, methotrexate, tamoxifen, valproic acid, tetracyclines 3
• Consider Wilson disease in patients <40 years: serum ceruloplasmin, 24-hour urinary copper, slit-lamp examination for Kayser-Fleischer rings 1
• Evaluate for autoimmune hepatitis if ALT persistently elevated: antinuclear antibody, anti-smooth muscle antibody, immunoglobulin G 1
• Check for hemochromatosis: transferrin saturation and ferritin 2
• Screen for α1-antitrypsin deficiency and celiac disease in appropriate clinical contexts 1, 2

Risk Stratification for Fibrosis (Critical Step)

Calculate FIB-4 Score

Use FIB-4 as the first-tier non-invasive test (age × AST / [platelet count × √ALT]) to stratify fibrosis risk 1, 2:

• Low risk: FIB-4 <1.3 (or <1.45 in some guidelines) 1, 2
• Intermediate risk: FIB-4 1.3-2.67 1, 2
• High risk: FIB-4 >2.67 1, 2

Additional Testing Based on FIB-4 Results

For intermediate or high-risk FIB-4 (≥1.3):

• Obtain vibration-controlled transient elastography (VCTE) liver stiffness measurement (LSM) or enhanced liver fibrosis blood test for further risk stratification 1, 2
• LSM <8 kPa: excludes advanced fibrosis 1, 2
• LSM 8-12 kPa: intermediate risk, requires hepatology follow-up 1, 2
• LSM >12 kPa: high probability of clinically significant fibrosis, refer to hepatology 1

For low-risk FIB-4 with persistently elevated ALT >6 months:

• Investigate other causes of liver disease beyond MASLD 1

Laboratory Workup

Baseline Testing

• Complete metabolic panel: AST, ALT, alkaline phosphatase, total bilirubin, albumin 1, 2
• Complete blood count with platelets (platelet count <150 G/L suggests portal hypertension) 1
• Fasting lipid panel and hemoglobin A1c 1, 2
• Thyroid-stimulating hormone to exclude hypothyroidism 1

Imaging

• Abdominal ultrasound to confirm steatosis and screen for hepatocellular carcinoma if cirrhosis suspected 1
• Look for signs of portal hypertension: splenomegaly, portosystemic collaterals, enlarged portal vein, ascites 1

Management Pathway Based on Risk Stratification

Low-Risk Patients (FIB-4 <1.3, LSM <8 kPa)

Can be managed in primary care with annual FIB-4 monitoring 2, 4:

• Implement lifestyle modifications: 500-1000 kcal/day deficit, Mediterranean diet, 150-300 minutes/week moderate-intensity exercise 2, 3
• Target 7-10% weight loss to improve steatohepatitis and potentially reverse fibrosis 2, 3
• Manage cardiometabolic comorbidities: use GLP-1 receptor agonists or SGLT2 inhibitors for diabetes, statins for dyslipidemia 2, 3

Intermediate/High-Risk Patients (FIB-4 ≥1.3 or LSM ≥8 kPa)

Refer to hepatology for specialized management 1, 2:

• Consider liver biopsy if diagnosis uncertain or to guide treatment decisions 2
• Patients with biopsy-proven steatohepatitis and significant fibrosis (≥F2) are candidates for pharmacotherapy: resmetirom, vitamin E, or pioglitazone 2, 3

Patients with Advanced Fibrosis/Cirrhosis (LSM >12 kPa or F3-F4)

Require comprehensive cirrhosis management 2:

• Hepatocellular carcinoma surveillance: ultrasound ± AFP every 6 months 1, 3
• Variceal screening: esophagogastroduodenoscopy if LSM >20 kPa or platelets <150 G/L 1
• Consider bariatric surgery for appropriate candidates with obesity and comorbidities 2, 4

Common Pitfalls to Avoid

• Do not rely solely on normal ALT to exclude significant fibrosis—up to 20% of patients with type 2 diabetes have clinically significant fibrosis despite normal transaminases 1
• Do not assume steatosis is benign—MASLD with fibrosis increases risk of hepatocellular carcinoma, cardiovascular disease, chronic kidney disease, and extrahepatic cancers 1
• Do not withhold statins—they are safe in MASLD and reduce hepatocellular carcinoma risk by 37% 3, 4
• Do not miss Wilson disease in young patients—hepatic steatosis in Wilson disease can mimic MASLD but requires urgent copper-chelating therapy 1