title: Serum fibrosis marker levels decrease after successful antiviral treatment in chronic hepatitis C patients with advanced fibrosis.
abstract: OBJECTIVE
  Serum fibrosis marker levels during the lead-in treatment phase of patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial were determined.
  
  
  METHODS
  Week 0, 24, 48, and 72 serum samples were analyzed for YKL-40, tissue inhibitor of matrix metalloproteinase-1, amino-terminal peptide of type III procollagen (PIIINP), and hyaluronic acid (HA) levels. All 456 chronic hepatitis C (CHC) patients received peginterferon alfa 2a and ribavirin for 24 to 48 weeks.
  
  
  RESULTS
  Mean age was 49.2 years, 71% were male, and 39% had cirrhosis. Lower pretreatment serum YKL-40, tissue inhibitor of matrix metalloproteinase-1, PIIINP, and HA levels were associated significantly with week-20 virologic response (P < .0001). In multivariate analysis, non-1 CHC genotype, non-black race, prior interferon monotherapy, and lower baseline serum aspartate aminotransferase/alanine aminotransferase levels and log(10)YKL-40 levels were associated independently with week-20 virologic response. Statistically significant declines in all marker levels were observed at week 72 compared with baseline in the 81 patients with a sustained virologic response, but not in the 72 patients with breakthrough or relapse. At weeks 24 and 48, significant increases were observed in serum PIIINP and HA levels compared with baseline in virologic responders and nonresponders (P < .0001).
  
  
  CONCLUSIONS
  Pretreatment YKL-40 levels are an independent predictor of initial virologic response to peginterferon and ribavirin treatment. Levels of all 4 serum fibrosis markers decreased significantly in the SVR patients, consistent with reduced hepatic fibrogenesis. Measuring serum fibrosis marker levels before and after antiviral therapy may provide important prognostic information in CHC patients.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0362, USA. rfontana@med.umich.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Deepa
authors.initials: D
authors.lastname: Naishadham
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
authors.forename: Grace L
authors.initials: GL
authors.lastname: Su
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a