Serum 25-hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load

被引:10
作者
Atsukawa, Masanori [1 ]
Tsubota, Akihito [2 ]
Shimada, Noritomo [3 ]
Kondo, Chisa [1 ]
Itokawa, Norio [1 ]
Nakagawa, Ai [1 ]
Hashimoto, Satomi [4 ]
Fukuda, Takeshi [4 ]
Matsushita, Yoko [4 ]
Narahara, Yoshiyuki [4 ]
Iwakiri, Katsuhiko [1 ]
Nakatsuka, Katsuhisa [4 ]
Kawamoto, Chiaki [4 ]
Sakamoto, Choitsu [4 ]
机构
[1] Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, Div Gastroenterol, Inzai, Japan
[2] Jikei Univ, Sch Med, ICMR, Kashiwa, Chiba, Japan
[3] Shinmatsudo Cent Gen Hosp, Div Gastroenterol & Hepatol, Matsudo, Chiba, Japan
[4] Nippon Med Sch, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 113, Japan
关键词
cirrhosis; hepatitis C virus; 25-hydroxyvitamin D-3; pegylated interferon; ribavirin; sustained virological response; SUSTAINED VIROLOGICAL RESPONSE; COMMON GENETIC-DETERMINANTS; GENOME-WIDE ASSOCIATION; VITAMIN-D; HEPATOCELLULAR-CARCINOMA; PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2B; NATURAL-HISTORY; SEVERE FIBROSIS; PEG-INTERFERON;
D O I
10.1111/hepr.12298
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AimMuch is unknown about the effect of 25-hydroxyvitamin D-3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus-related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25-hydroxyvitamin D-3, that contribute to a sustained virological response (SVR) in patients with cirrhosis. MethodsWe analyzed whether 25-hydroxyvitamin D-3 contributes to the response to PEG IFN/RBV therapy among 134 cirrhotic patients. ResultsSVR was achieved in 43 patients. The median 25-hydroxyvitamin D-3 level was 20ng/mL. Univariate analysis showed that the following factors contributed to SVR: low-density lipoprotein cholesterol, albumin, 25-hydroxyvitamin D-3, core a.a.70 (a.a.70) substitutions, the number of mutations at the interferon sensitivity-determining region and IL28B genotype. Multivariate analysis identified IL28B genotype and 25-hydroxyvitamin D-3 as independent factors contributing to SVR. Subsequently, SVR rate was examined by using 25-hydroxyvitamin D-3 and other important factors. The SVR rate was 51.8% in patients with core a.a.70 wild and 15ng/mL of 25-hydroxyvitamin D-3, whereas the SVR rate was 7.1% in patients with core a.a.70 wild and <15ng/mL of 25-hydroxyvitamin D-3. The SVR rate was 56.9% in patients with IL28B major genotype and 15ng/mL of 25-hydroxyvitamin D-3. Surprisingly, the SVR rate was 0% in patients with IL28B minor genotype and <15ng/mL of 25-hydroxyvitamin D-3. ConclusionIL28B genotype and 25-hydroxyvitamin D-3 were identified as independent factors contributing to SVR. Stratified analyses according to core a.a.70 substitution and IL28B genotype suggested that 25-hydroxyvitamin D-3 influences the outcome of PEG IFN/RBV therapy for cirrhosis.
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页码:1277 / 1285
页数:9
相关论文
共 47 条
[1]   Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b [J].
Abergel, A. ;
Hezode, C. ;
Leroy, V. ;
Barange, K. ;
Bronowicki, J. P. ;
Tran, A. ;
Alric, L. ;
Castera, L. ;
Bernard, P. -H. ;
Henquell, C. ;
Lafeuille, H. ;
Ughetto, S. ;
Darcha, C. ;
Chevallier, M. ;
Martineau, N. ;
Dubost, S. ;
Randl, K. ;
Dhumeaux, D. ;
Bommelaer, G. ;
Bonny, C. .
JOURNAL OF VIRAL HEPATITIS, 2006, 13 (12) :811-820
[2]   Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naive patients [J].
Abu-Mouch, Saif ;
Fireman, Zvi ;
Jarchovsky, Jacob ;
Zeina, Abdel-Rauf ;
Assy, Nimer .
WORLD JOURNAL OF GASTROENTEROLOGY, 2011, 17 (47) :5184-5190
[3]   Genome-wide association study of circulating vitamin D levels [J].
Ahn, Jiyoung ;
Yu, Kai ;
Stolzenberg-Solomon, Rachael ;
Simon, K. Claire ;
McCullough, Marjorie L. ;
Gallicchio, Lisa ;
Jacobs, Eric J. ;
Ascherio, Alberto ;
Helzlsouer, Kathy ;
Jacobs, Kevin B. ;
Li, Qizhai ;
Weinstein, Stephanie J. ;
Purdue, Mark ;
Virtamo, Jarmo ;
Horst, Ronald ;
Wheeler, William ;
Chanock, Stephen ;
Hunter, David J. ;
Hayes, Richard B. ;
Kraft, Peter ;
Albanes, Demetrius .
HUMAN MOLECULAR GENETICS, 2010, 19 (13) :2739-2745
[4]   Effect of Aging on Risk for Hepatocellular Carcinoma in Chronic Hepatitis C Virus Infection [J].
Asahina, Yasuhiro ;
Tsuchiya, Kaoru ;
Tamaki, Nobuharu ;
Hirayama, Itsuko ;
Tanaka, Tomohiro ;
Sato, Mitsuaki ;
Yasui, Yutaka ;
Hosokawa, Takanori ;
Ueda, Ken ;
Kuzuya, Teiji ;
Nakanishi, Hiroyuki ;
Itakura, Jun ;
Takahashi, Yuka ;
Kurosaki, Masayuki ;
Enomoto, Nobuyuki ;
Izumi, Namiki .
HEPATOLOGY, 2010, 52 (02) :518-527
[5]   An algorithm for the grading of activity in chronic hepatitis C [J].
Bedossa, P ;
Poynard, T .
HEPATOLOGY, 1996, 24 (02) :289-293
[6]   Complementary Role of Vitamin D Deficiency and the Interleukin-28B rs12979860 C/T Polymorphism in Predicting Antiviral Response in Chronic Hepatitis C [J].
Bitetto, Davide ;
Fattovich, Giovanna ;
Fabris, Carlo ;
Ceriani, Elisa ;
Falleti, Edmondo ;
Fornasiere, Ezio ;
Pasino, Michela ;
Ieluzzi, Donatella ;
Cussigh, Annarosa ;
Cmet, Sara ;
Pirisi, Mario ;
Toniutto, Pierluigi .
HEPATOLOGY, 2011, 53 (04) :1118-1126
[7]   Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C [J].
Bitetto, Davide ;
Fabris, Carlo ;
Fornasiere, Ezio ;
Pipan, Corrado ;
Fumolo, Elisa ;
Cussigh, Annarosa ;
Bignulin, Sara ;
Cmet, Sara ;
Fontanini, Elisabetta ;
Falleti, Edmondo ;
Martinella, Romina ;
Pirisi, Mario ;
Toniutto, Pierluigi .
TRANSPLANT INTERNATIONAL, 2011, 24 (01) :43-50
[8]   Sustained virological response to interferon-α is associated with improved outcome in HCV-related cirrhosis:: A retrospective study [J].
Bruno, Savino ;
Stroffolini, Tommaso ;
Colombo, Massimo ;
Bollani, Simona ;
Benvegnu, Luisa ;
Mazzella, Giuseppe ;
Ascione, Antonio ;
Santantonio, Teresa ;
Piccinino, Felice ;
Andreone, Pietro ;
Mangia, Alessandra ;
Gaeta, Giovanni B. ;
Persico, Marcello ;
Fagiuoli, Stefano ;
Almasio, Piero L. .
HEPATOLOGY, 2007, 45 (03) :579-587
[9]   Efficacy and safety of boceprevir plus peginterferon-ribavirin in patients with HCV G1 infection and advanced fibrosis/cirrhosis [J].
Bruno, Savino ;
Vierling, John M. ;
Esteban, Rafael ;
Nyberg, Lisa M. ;
Tanno, Hugo ;
Goodman, Zachary ;
Poordad, Fred ;
Bacon, Bruce ;
Gottesdiener, Keith ;
Pedicone, Lisa D. ;
Albrecht, Janice K. ;
Brass, Clifford A. ;
Thompson, Seth ;
Burroughs, Margaret H. .
JOURNAL OF HEPATOLOGY, 2013, 58 (03) :479-487
[10]   Efficacy and Safety of Peginterferon Alfa-2a (40KD) Plus Ribavirin in Hepatitis C Patients with Advanced Fibrosis and Cirrhosis [J].
Bruno, Savino ;
Shiffman, Mitchell L. ;
Roberts, Stuart K. ;
Gane, Edward J. ;
Messinger, Diethelm ;
Hadziyannis, Stephanos J. ;
Marcellin, Patrick .
HEPATOLOGY, 2010, 51 (02) :388-397