Noninvasive serum fibrosis markers for screening and staging chronic hepatitis C virus patients in a large US cohort

Abstract

Background: Liver biopsy remains critical for staging liver disease in hepatitis C virus (HCV)-infected persons, but is a bottleneck to evaluation, follow-up, and treatment of HCV. Our analysis sought to validate APRI (aspartate aminotransferase [AST]-to-platelet ratio index) and FIB-4, an index from serum fibrosis markers (alanine aminotransferase [ALT], AST, and platelets plus patient age) to stage liver disease.

Methods: Biopsy results from HCV patients in the Chronic Hepatitis Cohort Study were mapped to an F0-F4 equivalent scale; APRI and FIB-4 scores at the time of biopsy were then mapped to the same scale.

Results: We identified 2372 liver biopsies from HCV-infected patients with contemporaneous laboratory values for imputing APRI and FIB-4. Fibrosis stage distributions by the equivalent biopsy scale were 267 (11%) F0; 555 (23%) F1; 648 (27%) F2; 394 (17%) F3; and 508 (21%) F4. Mean APRI and FIB-4 values significantly increased with successive fibrosis levels (P < .05). The areas under the receiver operating characteristic curve (AUROC) analysis distinguishing severe (F3-F4) from mild-to-moderate fibrosis (F0-F2) were 0.80 (95% confidence interval [CI], .78-.82) for APRI and 0.83 (95% CI, .81-.85) for FIB-4. There was a significant difference between the AUROCs of FIB-4 and APRI (P < .001); 88% of persons who had a FIB-4 score ≥2.0 were at stage F2 or higher.

Conclusions: In a large observational cohort, FIB-4 was good at differentiating 5 stages of chronic HCV infection. It can be useful in screening patients who need biopsy and therapy, for monitoring patients with less advanced disease, and for longitudinal studies.

Keywords: chronic hepatitis; clinical staging; hepatitis C virus.

Figure 1

The predictive ability of 3 noninvasive methods for severe fibrosis. The areas under the receiver operating characteristic curve analysis in distinguishing severe fibrosis (stages F3 and F4) from mild-to-moderate fibrosis (stages F0–F2) were 0.80 (95% confidence interval [CI], .78–.82) for APRI, 0.83 (95% confidence interval [CI], .81–.85) for FIB-4, and 0.64 (95% CI, .61–.66) for aspartate aminotransferase/alanine aminotransferase ratio. Abbreviations: ALT, alanine aminotransferase; APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; FIB-4, an index from serum fibrosis markers; ROC, receiver operating characteristic.