Journal of Clinical Virology 56 (2013) 293–298 Contents lists available at SciVerse ScienceDirect Journal of Clinical Virology j ourna l ho mepage: www.elsevier.com/locate/jcv Profound week 4 interferon responsiveness is mandatory for hepatitis C genotype 1 patients with unfavorable IL-28B genotype Chung-Feng Huang a,b,c , Ming-Lung Yu b,d,e , Jia-Horng Kao f,g,h , Tai-Chung Tseng i , Ming-Lun Yeh b , Jee-Fu Huang b,d,j , Chia-Yen Dai b,d , Zu-Yau Lin b,d , Shinn-Cherng Chen b,d , Liang-Yen Wang b,d , Suh-Hang Hank Juo k,l , Wan-Long Chuang b,d , Chen-Hua Liu f,g,h,∗ a Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan b Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan c Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan d Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan e Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan f Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan g Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan h Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan i Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan j Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan k Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan l Department of Medical Genetics and Department of Neurology, Kaohsiung Medical University, Kaohsiung, Taiwan a r t i c l e i n f o Article history: Received 17 August 2012 Received in revised form 14 October 2012 Accepted 19 November 2012 Keywords: HCV Treatment IL28B a b s t r a c t Background: Viral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection. Objectives: We aimed to explore the interplay between interferon responsiveness at treatment week 4 and IL28B genotype in the achievement of a sustained virological response (SVR; undetectable HCV RNA 24-weeks after end-of-treatment). Study designs: Rs8099917 genotypes were determined in 528 HCV-1 patients with peginter- feron/ribavirin. Interferon responsiveness were evaluated by the degree of week 4 viral reduction: <1 log 10 IU/mL, 1–2 logs 10 IU/mL, 2–3 logs 10 IU/mL, 3–4 logs 10 IU/mL and ≥4 logs 10 IU/mL reduction and/or undetectable HCV RNA, respectively. Results: The SVR rate was significantly higher in patients with great interferon responsiveness at week 4. A great interferon responsiveness was associated with younger age (P < 0.0001), lower body mass index (P = 0.0056), lower aspartate aminotransferase levels (P = 0.0009), higher hemogloblin concentra- tion (P = 0.0033), higher platelet counts (P < 0.0001), male gender (P < 0.0001) and rs809997 TT-genotype (P < 0.0001). Comparing to non-TT genotype patients, TT genotype patients had a significantly higher SVR rate with moderate viral reduction (1–3 logs 10 IU/mL) at week 4 (58.9% vs. 18.2%, P < 0.001), and the SVR rate did not differ between TT/non-TT patients on the extreme ends (<1 or >3 log 10 IU/mL reduction) of week 4 interferon responsiveness. For non-TT genotype carriers who were with <3 logs 10 reduction, none (0/15) could have a complete early virological response and only 10.9% (7/64) of the patients had an SVR. Conclusions: More profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype. © 2012 Elsevier B.V. All rights reserved. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; APRI, the aspartate aminotransferase-to-platelet ratio index; CHC, chronic hepatitis C; cEVR, complete early virological response; EOTVR, end-of-treatment virological response; HCV, hepatitis C virus; IL-28B, interleukin 28B; PPV, positive predictive value; RVR, rapid virological response; NPV, negative predictive value; SNP, single nucleotide polymorphism; SVR, sustained virological response. ∗ Corresponding author at: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Tel.: +886 7 312 1101x7475; fax: +886 7 3123955. E-mail addresses: fishya@ms14.hinet.net, fish6069@gmail.com (C.-H. Liu). 1. Background Hepatitis C virus (HCV) infection is one of the most impor- tant causes of cirrhosis and hepatocellular carcinoma and has a strong impact on public health not only in Taiwan but also worldwide. 1 Successful eradication of HCV could effectively regress liver fibrosis, reduce hepatocarcinogenesis and prolong survival. 2–4 Several pretreatment demographic and viral parameters such as 1386-6532/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jcv.2012.11.015