Noninvasive Serum Fibrosis Markers for Screening and Staging Chronic Hepatitis C Virus Patients in a Large US Cohort

• Published in: Clinical infectious diseases 2013-07, Vol.57 (2), p.240-246
• Main Authors: Holmberg, Scott D., Lu, Mei, Rupp, Loralee B., Lamerato, Lois E., Moorman, Anne C., Vijayadeva, Vinutha, Boscarino, Joseph A., Henkle, Emily M., Gordon, Stuart C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Alanine Transaminase - blood; ARTICLES AND COMMENTARIES; Aspartate Aminotransferases - blood; Biological and medical sciences; Biomarkers - blood; Biopsy; Clinical Laboratory Techniques - methods; Female; Hepatitis; Hepatitis C; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - pathology; Human viral diseases; Humans; Infectious diseases; Liver Cirrhosis - diagnosis; Liver Cirrhosis - pathology; Liver diseases; Mass Screening - methods; Medical sciences; Medical screening; Middle Aged; Platelet Count; Serum - chemistry; Severity of Illness Index; United States; Viral diseases; Viral hepatitis; Young Adult
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cit245

Background. Liver biopsy remains critical for staging liver disease in hepatitis C virus (HSV)—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.