Jung Hyun Kwon1, Si Hyun Bae2, Youn Jae Lee3, Jin-Woo Lee4, Young Seok Kim5, Jae Seok Hwang6, Won Young Tak7, Jeong Won Jang8, Byung Seok Lee9, June Sung Lee10, Chun Kyon Lee11, Soon Koo Baik12, Neung Hwa Park13, Tae Hee Lee14, Dong Joon Kim15, Jae-Seok Choi16, Jae-Gook Shin17,18, Hyeon Woo Yim19. 1. Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea. doctorkwon@catholic.ac.kr. 2. Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-040, Korea. baesh@catholic.ac.kr. 3. Department of Internal Medicine, Pusan Paik Hospital, Inje University of Korea, Gaegum-dong 633-165, Busanjin-gu, Pusan, 614-735, Korea. yiyh0105@inje.ac.kr. 4. Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. jin@inha.ac.kr. 5. Department of Internal Medicine, Bucheon Soonchunhyang Hospital, Soonchunhyang University of Korea, Bucheon, Korea. liverkys@schmc.ac.kr. 6. Department of Internal Medicine, Dongsan Hospital, Keimyung University of Korea, Taegu, Korea. gastro@dsmc.or.kr. 7. Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University of Korea, Taegu, Korea. wytak@knu.ac.kr. 8. Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-040, Korea. garden@catholic.ac.kr. 9. Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University of Korea, Taejon, Korea. gie001@cnuh.co.kr. 10. Department of Internal Medicine, Ilsan Paik Hospital, Inje University of Korea, Ilsan, Korea. jsleemd@paik.ac.kr. 11. Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Ilsan, Korea. cklee33@nhimc.or.kr. 12. Department of Internal Medicine, Wonju Christian Hospital, Yonsei University of Korea, Wonju, Korea. baiksk@yonsei.ac.kr. 13. Department of Internal Medicine, Ulsan University Hospital, Ulsan University of Korea, Ulsan, Korea. nhpark@uuh.ulsan.kr. 14. Department of Internal Medicine, Konyang University Hospital, Konyang University of Korea, Taejon, Korea. green740@naver.com. 15. Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University of Korea, Chuncheon, Korea. djkim@hallym.ac.kr. 16. Department of Pharmacology and PharmacoGenomics Research Center, Inje University of Korea, Pusan, Korea. karis@hanmail.net. 17. Department of Pharmacology and PharmacoGenomics Research Center, Inje University of Korea, Pusan, Korea. phshinjg@gmail.com. 18. Department of Clinical Pharmacology, Busan Paik Hospital, Inje University of Korea, Pusan, Korea. phshinjg@gmail.com. 19. Clinical Research Coordinating Center for Catholic Medical Center, The Catholic University of Korea, Seoul, Korea. y1693@catholic.ac.kr.
Abstract
PURPOSE: A high rate of sustained viral response (SVR) in Koreans with chronic hepatitis C (CHC) is related to a favorable IL28B genotype. We compared two dosing strategies for peginterferon alfa-2a in Koreans with CHC and defined the combined effect of polymorphisms and dosing on the virological response. METHODS: A total of 178 treatment-naïve patients with CHC genotype 1 were prospectively enrolled. All patients were randomly assigned to treatment with one of two peginterferon alfa-2a regimens: 180 μg per week for 48 weeks (full-dose group) or 180 μg per week during the first 12 weeks followed by 135 μg per week for the next 36 weeks (dose-reduction group). Polymorphisms related to IL28B, ITPA, C20orf194 and SLC29A1 were studied. RESULTS:SVR rates did not differ between the full-dose and dose-reduction groups (56.5 and 51.2 %, respectively, p = 0.474). The frequency of additional reductions of the peginterferon dose because of adverse events was higher in the full-dose group than in the dose-reduction group. SVR rates in patients homozygous for the IL28B major allele were higher than those in patients for the other IL28B alleles. For patients with unfavorable IL28B genotypes, SVR was less likely to be achieved in the dose-reduction group than in the full-dose group. CONCLUSIONS: In Koreans with HCV genotype 1, the virological response to treatment did not differ between a full dose and reduced dose (≥80 % of full dose) of peginterferon alfa-2a. However, in the patients with unfavorable IL28B genotypes, the full-dose treatment of peginterferon alfa-2a may be beneficial.
RCT Entities:
PURPOSE: A high rate of sustained viral response (SVR) in Koreans with chronic hepatitis C (CHC) is related to a favorable IL28B genotype. We compared two dosing strategies for peginterferon alfa-2a in Koreans with CHC and defined the combined effect of polymorphisms and dosing on the virological response. METHODS: A total of 178 treatment-naïve patients with CHC genotype 1 were prospectively enrolled. All patients were randomly assigned to treatment with one of two peginterferon alfa-2a regimens: 180 μg per week for 48 weeks (full-dose group) or 180 μg per week during the first 12 weeks followed by 135 μg per week for the next 36 weeks (dose-reduction group). Polymorphisms related to IL28B, ITPA, C20orf194 and SLC29A1 were studied. RESULTS: SVR rates did not differ between the full-dose and dose-reduction groups (56.5 and 51.2 %, respectively, p = 0.474). The frequency of additional reductions of the peginterferon dose because of adverse events was higher in the full-dose group than in the dose-reduction group. SVR rates in patients homozygous for the IL28B major allele were higher than those in patients for the other IL28B alleles. For patients with unfavorable IL28B genotypes, SVR was less likely to be achieved in the dose-reduction group than in the full-dose group. CONCLUSIONS: In Koreans with HCV genotype 1, the virological response to treatment did not differ between a full dose and reduced dose (≥80 % of full dose) of peginterferon alfa-2a. However, in the patients with unfavorable IL28B genotypes, the full-dose treatment of peginterferon alfa-2a may be beneficial.
Authors: M P Manns; J G McHutchison; S C Gordon; V K Rustgi; M Shiffman; R Reindollar; Z D Goodman; K Koury; M Ling; J K Albrecht Journal: Lancet Date: 2001-09-22 Impact factor: 79.321
Authors: John G McHutchison; Michael Manns; Keyur Patel; Thierry Poynard; Karen L Lindsay; Christian Trepo; Jules Dienstag; William M Lee; Carmen Mak; Jean-Jacques Garaud; Janice K Albrecht Journal: Gastroenterology Date: 2002-10 Impact factor: 22.682
Authors: Jung Hyun Kwon; Si Hyun Bae; Jong Young Choi; Seung Kew Yoon; Kwan Soo Byun; Seung Woon Paik; Young Suk Lim; Han Chu Lee; Kwang Hyub Han; Kwan Sik Lee Journal: Korean J Intern Med Date: 2009-08-26 Impact factor: 3.165