TY - JOUR
T1 - Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection
AU - Nakagawa, Mina
AU - Sakamoto, Naoya
AU - Ueyama, Mayumi
AU - Mogushi, Kaoru
AU - Nagaie, Satoshi
AU - Itsui, Yasuhiro
AU - Azuma, Seishin
AU - Kakinuma, Sei
AU - Tanaka, Hiroshi
AU - Enomoto, Nobuyuki
AU - Watanabe, Mamoru
N1 - Funding Information:
This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology-Japan; the Japan Society for the Promotion of Science; the Ministry of Health, Labour and Welfare-Japan; the Japan Health Sciences Foundation; the Miyakawa Memorial Research Foundation; and the National Institute of Biomedical Innovation. The following hospitals participated in the Ochanomizu-Liver Conference Study Group: Oume City General Hospital, Kashiwa City Hospital, Kudanzaka Hospital, Showa General Hospital, Shuwa General Hospital, Soka Municipal Hospital, Tama-Nambu Chiiki Hospital, Tuchiura Kyodo General Hospital, Tokyo Kyosai Hospital, Tokyo Metropolitan Ohtsuka Hospital, Tokyo Metropolitan Fuchu Hospital, Tokyo Metropolitan Bokutoh Hospital, Toride Kyodo General Hospital, Nakano General Hospital, Hokushin General Hospital, Mishima Social Insurance Hospital, Musashino Red Cross Hospital, Yokosuka Kyosai Hospital, Yokohama City Minato Red Cross Hospital.
PY - 2010/6
Y1 - 2010/6
N2 - Background Pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin (RBV) therapy is currently the de-facto standard treatment for hepatitis C virus (HCV) infection. The aims of this study were to analyze the clinical and virological factors associated with a higher rate of response in patients with HCV genotype 1b infection treated with combination therapy. Methods We analyzed, retrospectively, 239 patients with chronic hepatitis C-1b infection who received 48 weeks of combination therapy. We assessed clinical and laboratory parameters, including age, gender, pretreatment hemoglobin, platelet counts, HCV RNA titer, liver histology, the number of interferon sensitivity determining region (ISDR) mutations and substitutions of the core amino acids 70 and 91. Drug adherence was monitored in each patient. We carried out univariate and multivariate statistical analyses of these parameters and clinical responses. Results On an intention-to-treat (ITT) analysis, 98 of the 239 patients (41%) had sustained virological responses (SVRs). Patients with more than two mutations in the ISDR had significantly higher SVR rates (P<0.01). Univariate analyses showed that stage of fibrosis, hemoglobin, platelet counts, ISDR mutations, serum HCV RNA level, and adherence to PEG-IFN plus RBV were significantly correlated with SVR rates. Multivariate analysis in subjects with good drug adherence extracted the number of ISDR mutations (two or more: odds ratio [OR] 5.181). Conclusions The number of mutations in the ISDR sequence of HCV-1b (≥2) is the most effective parameter predicting a favorable clinical outcome of 48-week PEGIFN plus RBV therapy in patients with HCV genotype 1b infection.
AB - Background Pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin (RBV) therapy is currently the de-facto standard treatment for hepatitis C virus (HCV) infection. The aims of this study were to analyze the clinical and virological factors associated with a higher rate of response in patients with HCV genotype 1b infection treated with combination therapy. Methods We analyzed, retrospectively, 239 patients with chronic hepatitis C-1b infection who received 48 weeks of combination therapy. We assessed clinical and laboratory parameters, including age, gender, pretreatment hemoglobin, platelet counts, HCV RNA titer, liver histology, the number of interferon sensitivity determining region (ISDR) mutations and substitutions of the core amino acids 70 and 91. Drug adherence was monitored in each patient. We carried out univariate and multivariate statistical analyses of these parameters and clinical responses. Results On an intention-to-treat (ITT) analysis, 98 of the 239 patients (41%) had sustained virological responses (SVRs). Patients with more than two mutations in the ISDR had significantly higher SVR rates (P<0.01). Univariate analyses showed that stage of fibrosis, hemoglobin, platelet counts, ISDR mutations, serum HCV RNA level, and adherence to PEG-IFN plus RBV were significantly correlated with SVR rates. Multivariate analysis in subjects with good drug adherence extracted the number of ISDR mutations (two or more: odds ratio [OR] 5.181). Conclusions The number of mutations in the ISDR sequence of HCV-1b (≥2) is the most effective parameter predicting a favorable clinical outcome of 48-week PEGIFN plus RBV therapy in patients with HCV genotype 1b infection.
KW - Chronic hepatitis C
KW - Combination therapy
KW - Hepatitis C virus (HCV)
KW - Interferon sensitivity determining region (ISDR)
KW - PEG-IFN plus RBV therapy
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U2 - 10.1007/s00535-009-0195-7
DO - 10.1007/s00535-009-0195-7
M3 - Article
C2 - 20112032
AN - SCOPUS:77955716832
VL - 45
SP - 656
EP - 665
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 6
ER -