Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial
dc.contributor.author | Welzel, Tania Mara | en_US |
dc.contributor.author | Morgan, Timothy R. | en_US |
dc.contributor.author | Bonkovsky, Herbert L. | en_US |
dc.contributor.author | Naishadham, Deepa | en_US |
dc.contributor.author | Pfeiffer, Ruth M. | en_US |
dc.contributor.author | Wright, Elizabeth C. | en_US |
dc.contributor.author | Hutchinson, Amy A. | en_US |
dc.contributor.author | Crenshaw, Andrew T. | en_US |
dc.contributor.author | Bashirova, Arman | en_US |
dc.contributor.author | Carrington, Mary | en_US |
dc.contributor.author | Dotrang, Myhanh | en_US |
dc.contributor.author | Sterling, Richard K. | en_US |
dc.contributor.author | Lindsay, Karen L. | en_US |
dc.contributor.author | Fontana, Robert John | en_US |
dc.contributor.author | Lee, William M. | en_US |
dc.contributor.author | Di Bisceglie, Adrian M. | en_US |
dc.contributor.author | Ghany, Marc G. | en_US |
dc.contributor.author | Gretch, David R. | en_US |
dc.contributor.author | Chanock, Stephen J. | en_US |
dc.contributor.author | Chung, Raymond T. | en_US |
dc.contributor.author | O'Brien, Thomas R. | en_US |
dc.date.accessioned | 2009-07-06T15:38:50Z | |
dc.date.available | 2010-08-02T17:56:56Z | en_US |
dc.date.issued | 2009-06 | en_US |
dc.identifier.citation | Welzel, Tania Mara; Morgan, Timothy R.; Bonkovsky, Herbert L.; Naishadham, Deepa; Pfeiffer, Ruth M.; Wright, Elizabeth C.; Hutchinson, Amy A.; Crenshaw, Andrew T.; Bashirova, Arman; Carrington, Mary; Dotrang, Myhanh; Sterling, Richard K.; Lindsay, Karen L.; Fontana, Robert J.; Lee, William M.; Di Bisceglie, Adrian M.; Ghany, Marc G.; Gretch, David R.; Chanock, Stephen J.; Chung, Raymond T.; O'Brien, Thomas R. (2009). "Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Potential conflict of interest: Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: T. R. Morgan is a consultant, is on the speaker's bureau, and receives research support; H. L. Bonkovsky receives research support; R. K. Sterling is a consultant, is on the speaker's bureau, and receives research support; K. L. Lindsay is a consultant and receives research support; R. J. Fontana is on the speaker's bureau; W. M. Lee receives research support; A. M. Di Bisceglie is a consultant and receives research support; R. T. Chung receives research support. Authors with no financial relationships to this project are T. M. Welzel, D. Naishadham, R. M. Pfeiffer, E. C. Wright, A. A. Hutchinson, A. T. Crenshaw, A. Bashirova, M. Carrington, M. Dotrang, M. G. Ghany, D. R. Gretch, S. J. Chanock, and T. R. O'Brien. ." Hepatology 49(6): 1847-1858. <http://hdl.handle.net/2027.42/63061> | en_US |
dc.identifier.issn | 0270-9139 | en_US |
dc.identifier.issn | 1527-3350 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/63061 | |
dc.description.abstract | Combination treatment with pegylated-interferon-alpha (PEG IFN-Α) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-Α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2 -2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders ( P = 0.006). Conclusion: Genetic polymorphisms in the interferon-Α pathway may affect responses to antiviral therapy of chronic hepatitis C. (H EPATOLOGY 2009.) | en_US |
dc.format.extent | 278882 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Hepatology | en_US |
dc.title | Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD | en_US |
dc.contributor.affiliationother | Division of Gastroenterology, University of California - Irvine, Irvine, CA, and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA | en_US |
dc.contributor.affiliationother | Departments of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, and Carolinas Medical Center, Charlotte, NC | en_US |
dc.contributor.affiliationother | New England Research Institutes, Watertown, MA | en_US |
dc.contributor.affiliationother | Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD | en_US |
dc.contributor.affiliationother | Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD | en_US |
dc.contributor.affiliationother | Core Genotyping Facility, NCI/Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD | en_US |
dc.contributor.affiliationother | Core Genotyping Facility, NCI/Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD | en_US |
dc.contributor.affiliationother | Department of Medicine, Johns Hopkins University, Baltimore, MD | en_US |
dc.contributor.affiliationother | Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick Inc., NCI-Frederick Inc., Frederick, MD | en_US |
dc.contributor.affiliationother | Computer Sciences Corp., Rockville, MD | en_US |
dc.contributor.affiliationother | Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA | en_US |
dc.contributor.affiliationother | Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA | en_US |
dc.contributor.affiliationother | Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX | en_US |
dc.contributor.affiliationother | Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO | en_US |
dc.contributor.affiliationother | Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD | en_US |
dc.contributor.affiliationother | Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA | en_US |
dc.contributor.affiliationother | Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA | en_US |
dc.contributor.affiliationother | Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA | en_US |
dc.contributor.affiliationother | Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD ; fax: 301-480-1917. ; 6120 Executive Boulevard, Room 6111, MSC 7246, Rockville, MD 20892 | en_US |
dc.identifier.pmid | 19434718 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/63061/1/22877_ftp.pdf | |
dc.identifier.doi | 10.1002/hep.22877 | en_US |
dc.identifier.source | Hepatology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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