title: 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.
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. sdh1@cdc.gov
authors.forename: Scott D
authors.initials: SD
authors.lastname: Holmberg
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Loralee B
authors.initials: LB
authors.lastname: Rupp
authors.forename: Lois E
authors.initials: LE
authors.lastname: Lamerato
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moorman
authors.forename: Vinutha
authors.initials: V
authors.lastname: Vijayadeva
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Boscarino
authors.forename: Emily M
authors.initials: EM
authors.lastname: Henkle
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D019411:Clinical Laboratory Techniques / Q000379:methods*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D010976:Platelet Count; D044967:Serum / Q000737:chemistry; D012720:Severity of Illness Index; D014481:United States; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: chronic hepatitis; clinical staging; hepatitis C virus