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

Scott D. Holmberg, Mei Lu, Loralee B. Rupp, Lois E. Lamerato, Anne C. Moorman, Vinutha Vijayadeva, Joseph A. Boscarino, Emily M. Henkle, Stuart C. Gordon

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)240-246
Number of pages7
JournalClinical Infectious Diseases
Issue number2
StatePublished - Jul 15 2013
Externally publishedYes


  • chronic hepatitis
  • clinical staging
  • hepatitis C virus

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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