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Relationship between the genetic variation in interleukin 28b and response to antiviral therapy in patients with chronic hepatitis C

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Chinese Medical Journal 2012年第13期125卷 2334-2338页

作者： XIE Jun-qiang GUO Xiao-yan ZHANG Xiao-hong LIN bing-liang XIE Dong-ying GAO Zhi-liang WANG Gen-shu ZHAO Zhi-xin Department of Infectious Diseases Third Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510630 China Department of Liver Transplantation Third Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510630 China

background Genetic variations at the interleukin 28b （IL-28b） locus are important in predicting outcome following therapy for chronic hepatitis C virus （HCV） infection. The aim of this research was to evaluate the role of IL-28b single nucleotide polymorphism （SNP） variations in Chinese patients undergoing pegylated interferon-a plus ribavirin （PEG-IFN-a/RbV） treatment. Methods To determine the effect of IL-28b variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-a/RbV therapy. Results The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response （SVR） group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response （NVR） group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse （Rel） group （P 〈0.05）. Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel （OR=10.95, 95% CI =4.12-29.11, P=1.5×10-7 and OR=3.93, 95% CI =1.86-8.32, P=-2.1×10-4 respectively）. The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT （P 〈0.001）. Conclusions The IL-28b SNP rs12979860 genotype was related to the effectiveness of HCV therapy： patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.

关键词： hepatitis C virus interleukin 28b genetic variation sustained virological response relapse

Individualization of chronic hepatitis C treatment according to the host characteristics

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World Journal of Gastroenterology 2014年第11期20卷 2839-2853页

作者： Nikolaos K Gatselis Kalliopi Zachou Asterios Saitis Maria Samara George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine School of MedicineUniversity of Thessaly41110 LarissaGreece Department of Pathology School of MedicineUniversity of Thessaly41110 LarissaGreece

Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people *** is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most common cause of liver failure and *** standardof-care treatment for chronic hepatitis C(CHC)has been changed during the last decade and direct acting antiviral drugs have already been ***,understanding of the pathogenesis of CHC has evolved rapidly during the last years and now several host factors are known to affect the natural history and response to *** genome-wide association studies have shown the important role of interleukin-28b and inosine triphosphatase in HCV *** present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment.

关键词： Chronic hepatitis C Hepatitis C virus host factors interleukin 28b Inosine triphosphatase Single nucleotide polymorphism

Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C

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World Journal of Gastroenterology 2017年第21期23卷 3815-3824页

作者： bogna Swiatek-Koscielna Ewelina Kaluzna Ewa Strauss Jerzy Nowak Iwona bereszyńska Ewelina Gowin Jacek Wysocki Jolanta Rembowska Dominika barcińska Iwona Mozer-Lisewska Danuta Januszkiewicz-Lewandowska Institute of Human Genetics Polish Academy of Sciences Department of General and Vascular Surgery Poznan University of Medical Sciences Department of Infectious Diseases Poznan University of Medical Sciences Department of Family Medicine Poznan University of Medical Sciences Department of Preventive Medicine Poznan University of Medical Sciences Department of Medical Diagnostics Department of Pediatric Oncology Hematology and Bone Marrow TransplantationPoznan University of Medical Sciences

AIM To evaluate the association of IFNL3(IL28b) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C(CHC).METHODS The study enrolled 196 CHC Polish patients(82 women and 114 men in age 20-64) infected with hepatitis C virus(HCV) genotype 1. They were treatment na?ve and qualified to pegylated interferon alpha(PEG-IFN-α) and ribavirin(RbV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase(ALT), asparagine aminotransferase(AST) and total bilirubin(TbIL). The analysis of response to therapy included: sustained virological response(SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms(SNPs)(rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons. RESULTS Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC(grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TbIL). It was demonstrated that the rs4803217 C allele is associated with SVR(C vs A: P < 0.0001; dose of C allele: P = 0.0002) and nonrelapse(C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients(P < 0.0001), whereas patients carrying A allele are sig

关键词： Hepatitis C virus Chronic hepatitis C Interferon lambda 3 interleukin 28b rs4803217

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C

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World Journal of Hepatology 2017年第5期9卷 252-262页

作者： Satoshi Yamagiwa Toru Ishikawa Nobuo Waguri Soichi Sugitani Hiroto Wakabayashi Shogo Ohkoshi Takashi Tsukishiro Toru Takahashi Toshiaki Watanabe Shuji Terai Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Department of Gastroenterology and Hepatology Saiseikai Niigata Daini Hospital Department of Gastroenterology and Hepatology Niigata City General Hospital Department of Gastroenterology and Hepatology Tachikawa General Hospital Department of Gastroenterology and Hepatology Takeda General Hospital Department of Internal Medicine Nippon Dental University Medical Hospital Department of Internal Medicine Itoigawa General Hospital Department of Internal Medicine Uonuma Hospital Watanabe Clinic

AIMTo evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODSThe present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RbV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. RESULTSAmong the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28b (IL28b) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28b TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RbV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28b (OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) an

关键词： Telaprevir Aged patients Hepatitis C virus genotype 1b interleukin 28b Simeprevir