Is FibroSure Plus (FibroTest) appropriate for evaluating fibrosis in a patient with CT evidence of hepatic steatosis, splenomegaly, and possible peri‑portal changes suggestive of non‑alcoholic steatohepatitis with early fibrosis?

FibroSure Plus Test Utility in This Clinical Context

FibroSure Plus (FibroTest) is not recommended as the optimal test for this patient with CT evidence of hepatic steatosis, splenomegaly, and possible peri-portal changes, because serum-based fibrosis markers including FibroTest are unreliable—they cannot distinguish between different levels of fibrosis, are prone to false-positive results from factors unrelated to fibrosis (such as active hepatitis or Gilbert syndrome), and are outperformed by elastography-based methods for detecting advanced fibrosis in NAFLD. 1

Why FibroSure/FibroTest Falls Short in This Scenario

Limited Diagnostic Accuracy

• The ACR Appropriateness Criteria explicitly state that serum tests like FibroTest/FibroSure "are not reliable because several factors not related to fibrosis (eg, active hepatitis or Gilbert syndrome) can contribute to false-positive test results and the serum tests cannot distinguish between different levels of fibrosis." 1
• While FibroTest has demonstrated moderate diagnostic accuracy in meta-analyses (AUROC 0.84 for bridging fibrosis across liver diseases), this performance is inferior to imaging-based elastography methods. 2

Imaging Already Suggests Advanced Disease

• Your patient has splenomegaly on CT—a morphologic sign of portal hypertension that typically appears only in advanced cirrhosis, not early fibrosis. 1
• Peri-portal changes further suggest more advanced disease than FibroTest can reliably stage. 1
• When imaging already demonstrates features concerning for advanced fibrosis or cirrhosis, adding a serum biomarker with limited ability to distinguish fibrosis stages provides minimal additional value. 1

What You Should Order Instead

First-Line: Calculate FIB-4 Score

• FIB-4 is the most validated, cost-free, first-line noninvasive test for identifying patients with low or high probability of advanced fibrosis in NAFLD, recommended by the AGA based on its simplicity and zero cost. 1
• Calculate FIB-4 using age, AST, ALT, and platelet count: (age × AST)/(platelets × √ALT). 1
• FIB-4 <1.3 (or <2.0 if age ≥65 years) reliably excludes advanced fibrosis with >90% negative predictive value—these patients can be reassessed in 2-3 years with lifestyle modifications. 1
• FIB-4 1.3-2.67 represents an indeterminate zone requiring secondary testing with elastography or Enhanced Liver Fibrosis (ELF) testing. 1
• FIB-4 >2.67 indicates high risk for advanced fibrosis and warrants immediate hepatology referral. 1

Second-Line: Vibration-Controlled Transient Elastography (VCTE/FibroScan)

• VCTE is the preferred second-tier test when FIB-4 falls in the indeterminate range or when imaging findings (like your patient's splenomegaly) suggest advanced disease despite a low FIB-4. 1
• VCTE has superior diagnostic accuracy compared to serum markers, with sensitivity of 87% and specificity of 91% for diagnosing cirrhosis (F4). 1
• Unlike FibroTest, VCTE can be combined with conventional ultrasound and performs well in patients with obesity, ascites, and NAFLD. 1
• VCTE cutoffs for clinical decision-making:
  • <8.0 kPa: Advanced fibrosis excluded
  • ≥12.0 kPa: High probability of advanced fibrosis, mandates hepatology referral
  • ≥15.0 kPa: Suggests cirrhosis
  • ≥20-25 kPa: Suggests clinically significant portal hypertension 1

Alternative: Enhanced Liver Fibrosis (ELF) Test

• If elastography is unavailable, ELF test is a validated blood-based alternative that outperforms FibroTest for detecting advanced hepatic fibrosis, particularly in patients with type 2 diabetes. 1
• ELF ≥9.8 indicates high risk for advanced fibrosis and warrants hepatology referral. 1
• The sequential FIB-4-then-ELF strategy correctly classifies 88% of cases while reducing unnecessary referrals. 1

Critical Clinical Context

Your Patient's Imaging Findings Demand Action

• Splenomegaly is a red flag that should prompt immediate calculation of FIB-4 followed by elastography, not a serum biomarker with limited staging ability. 1
• Peri-portal changes on CT suggest the patient may already have advanced fibrosis (F3-F4), which is the strongest predictor of future liver-related outcomes including hepatocellular carcinoma, decompensation, and death. 1
• Patients with advanced fibrosis require hepatocellular carcinoma surveillance every 6 months and variceal screening via upper endoscopy. 1

Common Pitfall to Avoid

• Do not order FibroSure/FibroTest when imaging already suggests advanced disease. The test cannot distinguish between intermediate fibrosis stages and will not change management when morphologic features of cirrhosis are already present. 1
• Do not delay elastography or hepatology referral while waiting for serum biomarker results in a patient with splenomegaly—this finding alone warrants expedited evaluation for portal hypertension and cirrhosis complications. 1

Recommended Diagnostic Algorithm for This Patient

1. Calculate FIB-4 immediately using existing laboratory values (age, AST, ALT, platelets). 1

2. Order VCTE (FibroScan) regardless of FIB-4 result, given the concerning CT findings of splenomegaly and peri-portal changes. 1

3. If VCTE ≥12.0 kPa or FIB-4 >2.67, refer immediately to hepatology for:

   • Hepatocellular carcinoma surveillance with ultrasound ± AFP every 6 months 1
   • Upper endoscopy for variceal screening 1
   • Consideration of liver biopsy if diagnostic uncertainty persists 1

4. Complete baseline laboratory evaluation while awaiting elastography:

   • Hepatitis B surface antigen and hepatitis C antibody 1
   • Fasting glucose and HbA1c to assess for diabetes 1
   • Complete metabolic panel including albumin and bilirubin 1
   • Platelet count (if not already obtained) 1

Bottom Line

Cancel the FibroSure Plus order and proceed directly to FIB-4 calculation followed by VCTE (FibroScan). The combination of hepatic steatosis, splenomegaly, and peri-portal changes on CT imaging demands a diagnostic approach that can accurately stage fibrosis and detect cirrhosis—capabilities that serum biomarkers like FibroTest simply do not possess. 1