title: Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.
abstract: OBJECTIVE
  The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes.
  
  
  METHODS
  Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 microg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality.
  
  
  RESULTS
  During the lead-in, >or=4-log(10) decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by >or=4 log(10) during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients.
  
  
  CONCLUSIONS
  Viral suppression by >or=4 log(10) with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.
authors.affiliation: Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA. mshiffma@vcu.edu
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: John C
authors.initials: JC
authors.lastname: Hoefs
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Deepa
authors.initials: D
authors.lastname: Naishadham
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control / Q000821:virology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000517:prevention & control / Q000821:virology; D017093:Liver Failure / Q000517:prevention & control / Q000821:virology; D008113:Liver Neoplasms / Q000517:prevention & control / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a