TY - JOUR
T1 - Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial
AU - Shiffman, Mitchell L.
AU - Morishima, Chihiro
AU - Dienstag, Jules L.
AU - Lindsay, Karen L.
AU - Hoefs, John C.
AU - Lee, William M.
AU - Wright, Elizabeth C.
AU - Naishadham, Deepa
AU - Everson, Gregory T.
AU - Lok, Anna S.
AU - Di Bisceglie, Adrian M.
AU - Bonkovsky, Herbert L.
AU - Ghany, Marc G.
N1 - Funding Information:
Funding Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers listed above), the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and the General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, and National Institutes of Health (grant numbers are listed above). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.
PY - 2009/12
Y1 - 2009/12
N2 - Background & Aims: 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 μg/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, ≥4-log10 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 ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions: Viral suppression by ≥4 log10 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.
AB - Background & Aims: 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 μg/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, ≥4-log10 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 ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions: Viral suppression by ≥4 log10 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.
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U2 - 10.1053/j.gastro.2009.08.067
DO - 10.1053/j.gastro.2009.08.067
M3 - Article
C2 - 19747918
AN - SCOPUS:70849104810
SN - 0016-5085
VL - 137
SP - 1986
EP - 1994
JO - Gastroenterology
JF - Gastroenterology
IS - 6
ER -