期刊文献+

Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

下载PDF
导出
摘要 AIM To determine whether hepatitis C virus(HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein(Big Dye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28 B gene rs12979860(Custom TaqM an 5' allelic discrimination assay; Applied Biosystems).RESULTS Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response(SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70(R70Q/H) or/and position 91(L91M). The favorable IL28 B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age(P < 0.001), urban residence(P = 0.004), IL28 B CC genotype(P < 0.001), absence of core mutations(P = 0.005), achievement of rapid virologic response(P < 0.001) and early virological response(P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age(P < 0.001), absence of core substitutions(P = 0.04) and IL28 B CC genotype(P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. CONCLUSION HCV core mutations can help distinguish between patients who can still benefit from the affordable IFNbased therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease. AIMTo determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients.METHODSOne hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5’ allelic discrimination assay; Applied Biosystems).RESULTSOf the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P &#x0003c; 0.001), urban residence (P = 0.004), IL28B CC genotype (P &#x0003c; 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P &#x0003c; 0.001) and early virological response (P &#x0003c; 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P &#x0003c; 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P &#x0003c; 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%.CONCLUSIONHCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.
出处 《World Journal of Gastroenterology》 SCIE CAS 2016年第37期8406-8413,共8页 世界胃肠病学杂志(英文版)
基金 Supported by PN-II-PT-PCCA-2011-3.2 Program,No.88/2012 HepGen "Investigation of viral and host markers of non-response to anti-viral treatment in chronic hepatitis C" funded by the Romanian Ministry of Education and Research
  • 相关文献

参考文献36

  • 1Hall TA.BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT[].Nucleic Acids Symposium Series.1999
  • 2Fried Michael W,Shiffman Mitchell L,Reddy K Rajender,Smith Coleman,Marinos George,Gon?ales Fernando L,H?ussinger Dieter,Diago Moises,Carosi Giampiero,Dhumeaux Daniel,Craxi Antonio,Lin Amy,Hoffman Joseph,Yu Jian.Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. The New England Quarterly . 2002
  • 3Navaneethan Udayakumar,Kemmer Nyingi,Neff Guy W.Predicting the probable outcome of treatment in HCV patients. Therapeutic advances in gastroenterology . 2009
  • 4Bruno S,Di Marco V,Iavarone M,Roffi L,Crosignani A,Calvaruso V,Aghemo A,Cabibbo G,ViganòM,Boccaccio V,CraxíA,Colombo M,Maisonneuve P.Survival of patients with HCVcirrhosis and sustained virologic response is similar to the general population. Journal of Hepatology . 2016
  • 5Ahmed El-Shamy,Hak Hotta.Impact of hepatitis C virus heterogeneity on interferon sensitivity:An overview[J].World Journal of Gastroenterology,2014,20(24):7555-7569. 被引量:5
  • 6Andrew J. Leidner,Harrell W. Chesson,Fujie Xu,John W. Ward,Philip R. Spradling,Scott D. Holmberg.??Cost‐effectiveness of hepatitis C treatment for patients in early stages of liver disease(J)Hepatology . 2015 (6)
  • 7Stephen J. Polyak,Susan McArdle,Shan-Lu Liu,Daniel G. Sullivan,Minjun Chung,Wolfgang T. Hofg?rtner,Robert L. Carithers Jr.,Brian J. McMahon,James I. Mullins,Lawrence Corey,David R. Gretch.Evolution of Hepatitis C Virus Quasispecies in Hypervariable Region 1 and the Putative Interferon Sensitivity-Determining Region during Interferon Therapy and Natural Infection. Journal of Virology . 1998
  • 8C. Nelson Hayes,Michio Imamura,Hiroshi Aikata,Kazuaki Chayama.Genetics of IL28B and HCV—response to infection and treatment. Nature Reviews Gastroenterology & Hepatology . 2012
  • 9Joy Peter,David R. Nelson.??Optimal interferon‐free therapy in treatment‐experienced chronic hepatitis C patients(J)Liver Int . 2015
  • 10Oscar C. Araujo,José J.F. Barros,Kycia M. do ó,Letícia C. Nabuco,Charles A. Luz,Renata M. Perez,Christian Niel,Cristiane A. Villela‐Nogueira,Natalia M. Araujo.??Genetic variability of hepatitis B and C viruses in Brazilian patients with and without hepatocellular carcinoma(J)J. Med. Virol. . 2014 (2)

二级参考文献30

  • 1Meetings[J].World Journal of Gastroenterology,2010,16(1). 被引量:25
  • 2KazuakiChayama,C NelsonHayes.Hepatitis C virus: How genetic variability affects pathobiology of disease[J]. Journal of Gastroenterology and Hepatology . 2011
  • 3Hashem B. El-Serag.Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma[J]. Gastroenterology . 2012 (6)
  • 4Masao Omata,Tatsuo Kanda,Ming-Lung Yu,Osamu Yokosuka,Seng-Gee Lim,Wasim Jafri,Ryosuke Tateishi,Saeed S. Hamid,Wan-Long Chuang,Anuchit Chutaputti,Lai Wei,Jose Sollano,Shiv Kumar Sarin,Jia-Horng Kao,Geoffrey W. McCaughan.APASL consensus statements and management algorithms for hepatitis C virus infection[J].Hepatology International.2012(2)
  • 5P.Tangkijvanich,P.Komolmit,V.Mahachai,K.Poovorawan,S.Akkarathamrongsin,Y.Poovorawan.Response‐guided therapy for patients with hepatitis C virus genotype 6 infection: a pilot study[J].Journal of Viral Hepatitis.2012(6)
  • 6Cameron J Schweitzer,T Jake Liang.Impact of host and virus genome variability on HCV replication and response to interferon[J].Current Opinion in Virology.2013
  • 7Soo Ryang Kim,Ahmed El-Shamy,Susumu Imoto,Ke Ih Kim,Yoshi-hiro Ide,Lin Deng,Ikuo Shoji,Yasuhito Tanaka,Yutaka Hasegawa,Mitsuhiro Ota,Hak Hotta.Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load[J].Journal of Gastroenterology.2012(10)
  • 8El-shamy, Ahmed,Kim, Soo-ryang,Ide, Yoshi-hiro,Sasase, Noriko,Imoto, Susumu,Deng, Lin,Shoji, Ikuo,Hotta, Hak.Polymorphisms of Hepatitis C Virus Non-Structural Protein 5A and Core Protein and Clinical Outcome of Pegylated-Interferon/Ribavirin Combination Therapy[J].EN.2011(1)
  • 9N. H.Nguyen,P.VuTien,R. T.Garcia,H.Trinh,H.Nguyen,K.Nguyen,B.Levitt,M. H.Nguyen.Response to pegylated interferon and ribavirin in Asian American patients with Chronic hepatitis C genotypes 1 vs 2/3 vs 6[J].Journal of Viral Hepatitis.2010(10)
  • 10Enomoto, Nobuyuki,Maekawa, Shinya.HCV Genetic Elements Determining the Early Response to Peginterferon and Ribavirin Therapy[J].Intervirology.2010(1)

共引文献24

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部