Association of Amino Acid Substitution Pattern in Core Protein of Hepatitis C Virus Genotype 1b High Viral Load and Non-Virological Response to Interferon-Ribavirin Combination Therapy

Vol. 48, No. 6, 2005

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Original Paper

Association of Amino Acid Substitution Pattern in Core Protein of Hepatitis C Virus Genotype 1b High Viral Load and Non-Virological Response to Interferon-Ribavirin Combination Therapy
Norio Akuta^a, Fumitaka Suzuki^a, Hitomi Sezaki^a, Yoshiyuki Suzuki^a, Tetsuya Hosaka^a, Takashi Someya^a, Masahiro Kobayashi^a, Satoshi Saitoh^a, Sachiyo Watahiki^b, Junko Sato^b, Marie Matsuda^b, Mariko Kobayashi^b, Yasuji Arase^a, Kenji Ikeda^a, Hiromitsu Kumada^a

^aDepartment of Gastroenterology and
^bLiver Research Laboratory, Toranomon Hospital, Tokyo, Japan

Address of Corresponding Author

Intervirology 2005;48:372-380 (DOI: 10.1159/000086064)

Key Words

Hepatitis C virus
Genotype 1b
Albumin
Core region
Interferon sensitivity-determining region
Interferon
Ribavirin
Non-virological responder
Viral kinetics

Abstract

Objective: Patients with high titer (100 kIU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve highly sustained virological response rates to combination therapy with interferon plus ribavirin. Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs. Methods: We evaluated 50 consecutive Japanese adults with high titer of HCV genotype 1b who received combination therapy for 48 weeks. We investigated the pretreatment substitution patterns in amino acids 1-191 of the core region and amino acids 2209-2248 of NS5A, and early viral kinetics. Results: Overall, a non-virological response was noted in 12 (24%) patients. Multivariate analysis identified serum albumin <3.9 g/dl, substitutions of amino acid 70 in the core region, and substitutions of amino acid 91 as independent and significant factors associated with a non-virological response. Especially, substitutions of arginine (R) by glutamine (Q) at amino acid 70, and/or leucine (L) by methionine (M) at amino acid 91 were significantly more common in NVRs. The falls in HCV-RNA levels during treatment in patients with specific substitutions in the core region were significantly less than in those without such substitutions. Conclusions: Our results suggest that serum albumin and amino acid substitution patterns in the core region in patients with high titers of HCV genotype 1b may have an effect on combination therapy in NVRs. Further large-scale studies are required to examine the role of amino acid substitutions specific to a non-virological response to combination therapy.

Author Contacts

Norio Akuta, MD
Department of Gastroenterology, Toranomon Hospital
2-2-2 Toranomon, Minato-ku
Tokyo 105-0001 (Japan)
Tel. +81 44 877 5111, Fax +81 44 860 1623, E-Mail akuta-gi@umin.ac.jp

Article Information

Received: November 10, 2004
Accepted after revision: December 9, 2004
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 4, Number of References : 42

Medline Abstract (ID 16024941)

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