Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial
Everson, Gregory T.; Hoefs, John C.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Naishadham, Deepa; Shiffman, Mitchell L.; Kahn, Jeffrey A.; Lok, Anna Suk-Fong; Di Bisceglie, Adrian M.; Lee, William M.; Dienstag, Jules L.; Ghany, Marc G.; Morishima, Chihiro
2006-12
Citation
Everson, Gregory T.; Hoefs, John C.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Naishadham, Deepa; Shiffman, Mitchell L.; Kahn, Jeffrey A.; Lok, Anna S. F.; Di Bisceglie, Adrian M.; Lee, William M.; Dienstag, Jules L.; Ghany, Marc G.; Morishima, Chihiro (2006). "Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial Potential conflict of interest: Dr. Everson is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche. Dr. Shiffman is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche. He also advises for and received grants from Schering-Plough. He is a consultant and advises for Valeant. He also advises for Novartis. Dr. Hoefs is on the speakers' bureau of Roche. Dr. Bonkovsky is on the speaker's bureau of and received grants from Roche. He is on the speakers' bureau of Schering-Plough. Dr. Kahn is on the speakers' bureau of Gilead. He is a consultant and is on the speakers' bureau of Roche. Dr. Lok is a consultant for, advises, and received grants from Roche, GlaxoSmithKline, Gilead, Idenix, Innogenetics, and Bristol-Myers Squibb. She received grants from Schering-Plough and Valeant. She owns stock in, is a consultant, and advises for Andays. She is a consultant and advises for Pharmasset. Dr. Di Bisceglie is a consultant for and received grants from Roche. Dr. Lee received grants from Roche ." Hepatology 44(6): 1675-1684. <http://hdl.handle.net/2027.42/55880>
Abstract
In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon ± RBV and had Ishak fibrosis scores ≥ 3. Four groups of patients with increasingly severe liver disease were compared: (A) bridging fibrosis (Ishak 3 and 4) with platelet counts >125,000/mm 3 (n = 559); (B) bridging fibrosis with platelet counts ≤125,000/mm 3 (n = 96); (C) cirrhosis (Ishak 5 and 6) with platelet counts >125,000/mm 3 (n = 198); and (D) cirrhosis with platelet counts ≤125,000/mm 3 (n = 193). SVR rates were 23%, 17%, 10%, and 9% in groups A, B, C, and D, respectively ( P < .0001 for trend). Reduction in SVR as a function of increasingly severe disease was independent of age, percent African American, HCV genotype, HCV level, and type of prior therapy. Dose reduction lowered SVR frequencies, but to a lesser extent than disease severity. By logistic regression, cirrhosis ( P < .0001) was the major determinant that impaired virologic response, independent of dose reduction or platelet count. In conclusion , disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these “difficult-to-cure” patients. (H EPATOLOGY 2006;44:1675–1684.)Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0270-9139 1527-3350
Other DOIs
PMID
17133499
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17133499&dopt=citationMetadata
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