October 23, 2010

High ability to predict the treatment outcome of peginterferon and ribavirin combination therapy based on the reduction in HCV RNA levels at 4 weeks after starting therapy and amino acid substitutions in the hepatitis C virus in patients infected with HCV genotype 1b

J Gastroenterol. 2010 Oct 7. [Epub ahead of print]

Toyoda H, Kumada T, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Tada T, Arakawa T, Fujimori M, Niinomi T, Ando N, Yasuda S, Sakai K, Kimura J.

Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan, hmtoyoda@spice.ocn.ne.jp.

Abstract

BACKGROUND: The ability to predict the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on the reduction in hepatitis C virus (HCV) RNA levels at 4 weeks after starting the therapy and amino acid substitutions in HCV was to be confirmed.

METHODS: We measured the reduction in HCV RNA levels at 4 weeks after starting the combination therapy, as well as examining amino acid substitutions at residue 70 in the HCV core and within the interferon sensitivity-determining region (ISDR) of HCV non-structural protein 5A (NS5A), for 101 patients infected with HCV genotype 1b. The ability of these factors to predict a sustained virologic response (SVR) was analyzed.

RESULTS: When a 3 log(10) reduction in HCV RNA levels at 4 weeks after starting therapy was set as the cut-off value, an SVR was achieved in 37 of the 46 patients (80.4%) with a ≥3 log(10) decrease and in 4 of the 55 patients (7.3%) with a <3 log(10) decrease. All 4 patients who achieved an SVR despite a <3 log(10) reduction in HCV RNA levels at 4 weeks had an arginine at residue 70 in the HCV core and a non-wild-type sequence for the ISDR of HCV NS5A.

CONCLUSION: A ≥3 log(10) reduction in HCV RNA levels at 4 weeks after starting therapy indicates that a patient has a high likelihood of achieving an SVR as a final outcome. Additional information on the amino acid substitutions at residue 70 in the HCV core and within NS5A-ISDR will further increase the ability to predict a clinical response.

PMID: 20927636 [PubMed - as supplied by publisher]

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