Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.
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.
Shiffman
Mitchell L
ML
Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA. mshiffma@vcu.edu
Morishima
Chihiro
C
Dienstag
Jules L
JL
Lindsay
Karen L
KL
Hoefs
John C
JC
Lee
William M
WM
Wright
Elizabeth C
EC
Naishadham
Deepa
D
Everson
Gregory T
GT
Lok
Anna S
AS
Di Bisceglie
Adrian M
AM
Bonkovsky
Herbert L
HL
Ghany
Marc G
MG
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
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