title: Final results of a double-blind, placebo-controlled trial of the antifibrotic efficacy of interferon-gamma1b in chronic hepatitis C patients with advanced fibrosis or cirrhosis.
abstract: Interferon-gamma1b (IFN-gamma1b) is a pleiotropic cytokine that displays antifibrotic, antiviral, and antiproliferative activity. A total of 502 patients with compensated liver disease and an Ishak fibrosis score of 4-6 were randomized in a double-blind, placebo-controlled study, and 488 of these patients received subcutaneous injections of IFN-gamma1b 100 microg (group 1, n=169), IFN-gamma1b 200 microg (group 2, n=157), or placebo (group 3, n=162) 3 times a week for 48 weeks. Most patients (83.6%) had cirrhosis at baseline (Ishak score=5 or 6). Posttreatment liver biopsies were assessed in a blinded fashion for a reduction of 1 or more Ishak points (primary endpoint). Four hundred twenty patients with pretreatment and posttreatment liver biopsies were evaluable and showed no improvement in Ishak score between the 3 treatment groups (12.1%, 12.4%, and 16% of patients in groups 1, 2, and 3, respectively; P>0.05). Analysis of IFN-gamma-inducible biomarkers revealed that interferon-inducible T cell-alpha chemoattractant (ITAC), an IFN-gamma-inducible CXCR3 chemokine was an independent predictor of stable or improving Ishak score. IFN-gamma1b was well tolerated. There were similar numbers of deaths in all 3 arms (5, 5, and 4, respectively), and most were related to complications of cirrhosis.
  
  
  CONCLUSIONS
  IFN-gamma1b therapy was not able to reverse fibrosis in patients with advanced liver disease for 1 year. Subgroups of patients with elevated ITAC levels and perhaps less advanced disease may be considered for future studies with IFN-gamma1b.
authors.affiliation: Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA 92037, USA. pockros.paul@scrippshealth.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pockros
authors.forename: Lennox
authors.initials: L
authors.lastname: Jeffers
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Goodman
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gish
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Robert
authors.initials: R
authors.lastname: Reindollar
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Sarah
authors.initials: S
authors.lastname: Sullivan
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Blatt
authors.forename: Sima
authors.initials: S
authors.lastname: Faris-Young
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral; D011994:Recombinant Proteins; D007371:Interferon-gamma