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Pretreatment prediction of the outcome of response‐guided peginterferon‐α and ribavirin therapy for chronic hepatitis C
Author(s) -
Masaki Naohiko,
Sugiyama Masaya,
Shimada Noritomo,
Tanaka Yasuhito,
Nakamuta Makoto,
Izumi Namiki,
Watanabe Sumio,
Tsubota Akihito,
Komatsu Masafumi,
Masaki Tsutomu,
Enomoto Nobuyuki,
Yoneda Masashi,
Murata Kazumoto,
Ito Kiyoaki,
Koike Kazuhiko,
Mizokami Masashi
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12646
Subject(s) - ribavirin , medicine , genotype , gastroenterology , genotyping , chronic hepatitis , multivariate analysis , logistic regression , hepatitis c virus , antiviral therapy , odds ratio , virology , immunology , virus , gene , biology , genetics
Abstract Background and Aim The accuracy for predicting virological outcomes of peginterferon‐α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL 28 B genotyping. Our in vitro study revealed that the numbers of ( TA ) dinucleotide repeats [( TA )n] of rs72258881, which is located in the promoter region of IL 28 B gene, might regulate IL 28 B transcription. We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response‐guided clinical settings. Methods A nationwide, multi‐center prospective study in J apan determined IL 28 B (rs8099917) genotype, ( TA )n of rs72258881, and amino acid substitutions of hepatitis C virus and used these for multivariate analysis together with other parameters at pretreatment. Results After enrolling 215 patients with genotype 1 and high viral load from 23 hospitals between O ctober 2009 and F ebruary 2011, intent‐to‐treat analysis identified 202 patients in whom the final virological outcomes could be determined. Non‐virological response by non‐ TT genotype was predicted with 79.7% accuracy. When combined with the ( TA )n, the incidences of virological response tended to be higher in the longer ( TA )n group, regardless of rs8099917 genotype. Multivariate logistic regression analysis revealed that rs8099917 non‐ TT genotype ( P < 0.001), shorter ( TA )n ( P = 0.011), mutation of amino acid 70 in the virus core region ( P = 0.029), and lower levels of serum albumin ( P = 0.036) were independently associated with non‐virological response. Conclusions IL 28 B genotype and ( TA )n of rs72258881 may independently affect virological outcomes of peginterferon‐α and ribavirin as host factors, even in response‐guided therapy.