Polymorphisms of Hepatitis C Virus Non-Structural Protein 5A and Core Protein and Clinical Outcome of Pegylated-Interferon/Ribavirin Combination TherapyEl-Shamy A.a, c · Kim S.-R.b · Ide Y.-H.a · Sasase N.b · Imoto S.b · Deng L.a · Shoji I.a · Hotta H.a
aDivision of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, and bDivision of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan; cDepartment of Virology, Suez Canal University Faculty of Veterinary Medicine, Ismalia, Egypt
Hak Hotta, MD, PhD
Division of Microbiology, Center for Infectious Diseases
Kobe University Graduate School of Medicine
7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)
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Objective: Hepatitis C virus (HCV genome) polymorphisms are thought to influence the outcome of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy. This study aimed to examine non-structural protein 5A (NS5A) polymorphisms, e.g. IFN/RBV resistance-determining region (IRRDR) and IFN sensitivity-determining region (ISDR), and core protein polymorphism as predictive therapeutic markers. Methods: Pretreatment sequences of NS5A and core regions were analyzed in 68 HCV-1b-infected patients treated with PEG-IFN/RBV. Results: Of 24 patients infected withHCV having an IRRDR with 6 or more mutations (IRRDR≧6), 18 (75%) patients achieved sustained virological response (SVR), whereas only 11 (25%) of 44 patients infected with HCV having IRRDR≤5 did. IRRDR≧6 was significantly associated with SVR (p < 0.0001). On the other hand, ISDR≧2 was significantly associated with relapse (either before [breakthrough] or after end-of-treatment response [ETR[-]relapse]) (p < 0.05) and a point mutation of the core protein from Arg to Gln at position 70 (Gln70) was significantly associated with null-response (p < 0.05). Multivariate analysis identified IRRDR≧6 as the only viral genetic factor that independently predicted SVR. Conclusion: NS5A (IRRDR and ISDR) and core protein polymorphisms are associated with the outcome of PEG-IFN/RBV therapy for chronic hepatitis C. In particular, IRRDR≧6 is a useful marker for prediction of SVR.
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