title: Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial.
abstract: OBJECTIVE
  The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies.
  
  
  METHODS
  The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (≥10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies). Individual slopes were calculated if duration from first to last biopsy was > 4 years.
  
  
  RESULTS
  The RFSP as average fibrosis score vs average time in intervals (0-3 and >3 years prestudy, screening, month 24 and 48 on-study) in 455 patients in cohorts of baseline Ishak score ranged from 0.005 with Ishak score 2 to 0.124 with Ishak 6. The RFSP in individual patients (-0.35 to +0.97 Ishak units/year) had a mean of 0.12 ± 0.23 in 344 patients with prestudy and on-study biopsies (group A) and only 0.17 ± 0.22 in 169 with prestudy and screening biopsies (group B). Group A patients with RFSP slope ≥ 0.2 (95 patients, 27.6%) had higher 7-year cumulative rates of non-hepatocellular carcinoma outcomes (46% vs 8%, respectively) and with a hepatocellular carcinoma (10% vs 3%, respectively) than RFSP slope < 02 (249 patients, 72.4%) (P < .0001). RFSP and screening Ishak score correlated independently (P <.0001) with clinical outcomes in multivariate analysis.
  
  
  CONCLUSIONS
  Rapid RFSP (>0.2), which occurred in 26.7% of HALT-C Trial patients, correlated strongly with clinical outcomes.
authors.affiliation: Division of Gastroenterology, University of California-Irvine, Irvine, California, USA. jchoefs@uci.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Hoefs
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Goodman
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stoddard
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000473:pathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology / Q000517:prevention & control*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D015995:Prevalence; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a