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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 Corresponding Author
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)
Tel. +81 78 382 5500, Fax +81 78 382 5519, E-Mail email@example.com
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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