What is the typical workup for a patient with presumed fatty liver disease found on ultrasound?

Workup for Presumed Fatty Liver on Ultrasound

When fatty liver is incidentally found on ultrasound, immediately obtain comprehensive liver biochemistry (ALT, AST, GGT, alkaline phosphatase, bilirubin, albumin), calculate the FIB-4 score to risk-stratify for advanced fibrosis, screen for metabolic syndrome components, and exclude secondary causes of steatosis through targeted testing. 1, 2

Recognize Ultrasound Limitations

Ultrasound has significant diagnostic limitations that must be acknowledged before proceeding:

• Ultrasound has only 53-65% sensitivity for mild steatosis and frequently produces false positives, with 48-72% of patients with "mild" steatosis on ultrasound having negative confirmatory imaging 3, 2
• In patients with chronic liver disease, echogenic abnormalities are more likely due to fibrosis or inflammation rather than fat, with 66-69% of patients labeled as "fatty liver" actually having significant fibrosis or inflammation 4
• 83% of patients with negative ultrasound may still have histologic steatosis 3

Initial Laboratory Workup

Obtain the following tests immediately upon discovering fatty liver on ultrasound:

• Complete metabolic panel including ALT, AST, GGT, alkaline phosphatase, bilirubin, and albumin to assess liver function and calculate fibrosis scores 1, 2
• Complete blood count with platelet count (required for FIB-4 calculation) 1, 5
• Fasting lipid panel, fasting glucose or HbA1c to screen for metabolic syndrome 1, 6
• Hepatitis B surface antigen, hepatitis C antibody to exclude viral hepatitis 1
• Consider iron studies, autoimmune markers (ANA, anti-smooth muscle antibody), and ceruloplasmin if clinical suspicion exists for alternative diagnoses 1

Calculate FIB-4 Score for Risk Stratification

The FIB-4 score is the most validated and cost-effective initial test to stratify fibrosis risk, using age, AST, ALT, and platelet count 1, 5:

• FIB-4 <1.3 indicates low probability of advanced fibrosis (sensitivity 77.8%, specificity 71.2%) and allows for conservative management 5
• FIB-4 >1.3 requires further evaluation with either transient elastography or referral to hepatology 1, 5
• FIB-4 >2.67 indicates high probability of advanced fibrosis and mandates hepatology referral 1

Note that 20-58% of patients fall into intermediate values, limiting definitive risk stratification 5.

Screen for Metabolic Risk Factors

Assess for all components of metabolic syndrome, as these drive disease progression and mortality:

• Body mass index (BMI) - obesity is a primary risk factor 1, 2
• Type 2 diabetes - strongly associated with advanced fibrosis (43.5% vs 21.4% in non-diabetics) and requires screening regardless of liver enzyme levels 1, 7
• Hypertension, dyslipidemia, and central obesity - presence of ≥2 metabolic risk factors significantly increases cirrhosis and hepatocellular carcinoma risk 1, 2
• Detailed alcohol intake history - must exclude alcoholic liver disease (>20g/day for women, >30g/day for men) 2

Advanced Imaging When Indicated

For patients with FIB-4 >1.3 or high metabolic risk:

• Transient elastography (FibroScan) with controlled attenuation parameter (CAP) simultaneously quantifies fat content and liver stiffness, providing superior assessment compared to ultrasound alone 1, 2, 5
• MRI with proton density fat fraction (MRI-PDFF) is superior to ultrasound for detecting mild steatosis (<30% fat) and provides accurate quantification 1, 8
• MR elastography (MRE) provides the most accurate non-invasive measure of fibrosis when other tests are indeterminate 5

Hepatology Referral Criteria

Refer to hepatology when:

• FIB-4 >1.3 or indeterminate fibrosis scores 1, 5
• Persistently elevated ALT/AST (>1.5x upper limit of normal) 1
• Type 2 diabetes with any degree of steatosis 1, 7
• Age >50 years with metabolic syndrome 1
• Evidence of advanced fibrosis on elastography 1, 5

Critical Pitfalls to Avoid

• Do not rely solely on ultrasound findings - 18% of patients with incidental steatosis have significant fibrosis (≥F2), yet fewer than 1 in 3 receive appropriate hepatology evaluation 7
• Do not assume normal ALT excludes significant disease - ALT and BMI do not reliably predict fibrosis severity 7
• Do not delay evaluation in diabetic patients - diabetes is the strongest predictor of advanced fibrosis, independent of transaminase levels 1, 7
• Do not ignore "mild" steatosis on ultrasound - nearly half of patients with mild steatosis by ultrasound have moderate steatosis on definitive testing 3

Follow-Up Strategy

• Low-risk patients (FIB-4 <1.3, no metabolic risk factors): Repeat liver function tests and FIB-4 in 6-12 months 2
• Intermediate/high-risk patients: More frequent monitoring every 3-6 months with consideration for elastography or hepatology referral 2
• All patients: Optimize metabolic conditions (diabetes control, weight loss, lipid management) as primary therapy 1, 2