IL28B polymorphism may guide pegylated interferon plus ribavirin therapy even after curative treatment for hepatitis C virus-related hepatocellular carcinoma

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

T. Kawaoka^1,2, H. Aikata¹, S. Takaki¹, A. Hiramatsu¹, K. Waki¹, N. Hiraga¹, D. Miki^1,2, M. Tsuge¹, M. Imamura¹, Y. Kawakami¹, S. Takahashi¹, H. Ochi^1,2, H. Tashiro³, H. Ohdan³, K. Chayama^1,2

Article first published online: 23 MAY 2011

DOI: 10.1111/j.1365-2893.2011.01468.x

© 2011 Blackwell Publishing Ltd

Author Information

¹ Department of Medicine and Molecular Science, Division of Frontier Medical Science, Minami-ku, Hiroshima University, Hiroshima, Japan

² Laboratory for Digestive Diseases, Centre for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Minami-ku, Hiroshima, Japan

³ Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan

* Correspondence: Hiroshi Aikata, MD, Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail: aikata@hiroshima-u.ac.jp

Abstract

Keywords:
curative treatment; hepatitis C virus; hepatocellular carcinoma; interleukin-28B; pegylated interferon-alpha plus ribavirin combination therapy

Summary.  The present study was designed to determine the predictive factors for the viral response to pegylated interferon-alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV-genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013] for patients with genotype 1. Multivariate analysis identified male gender (OR 8.72, P = 0.001) and interleukin-28B (IL-28B) genotype (rs8099917) TT (OR 7.93, P = 0.007) as independent predictors of pEVR. Multivariate analysis also identified IL-28B genotype GG+TG (OR 14.1, P = 0.021) and α-fetoprotein >30 (OR 5.4, P = 0.031) as independent predictors of null response. Patients with SVR showed a better survival rate than those without SVR (P = 0.034). The second HCC recurrence rate tended to be lower in patients with SVR than in those without SVR (P = 0.054). With regard to the prognosis of patients with SVR, it is desirable to achieve SVR with interferon therapy even when administered after HCC treatment. IL-28B genotype is a potentially useful marker for the response to PEGIFN/RBV therapy administered after curative treatment of HCV-related HCC.

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