Premium
Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection
Author(s) -
Murakami Takeshi,
Enomoto Nobuyuki,
Kurosaki Masayuki,
Izumi Namiki,
Marumo Fumiaki,
Sato Chifumi
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300405
Subject(s) - ns5a , hepatitis c virus , interferon , virology , hepacivirus , genotype , hepatitis c , flaviviridae , virus , medicine , gene , biology , genetics
An association has been reported between mutations in the amino acid residues 2209‐2248 of the nonstructural protein 5A (NS5A) gene (interferon‐sensitivity determining region [ISDR]) and interferon efficacy in hepatitis C virus (HCV)‐1b infection. This relationship was analyzed in chronic HCV‐2 infection. Forty patients with HCV‐2a and 35 with HCV‐2b were treated with interferon alfa for 6 months with a total dose of 468 to 860 million units. Pretreatment NS5A sequences were determined by direct sequencing. A higher complete and sustained response rate was observed in HCV‐2a than in HCV‐2b (70% vs. 34%; P = .003). Serum HCV‐RNA levels were lower in complete responders than nonresponders in HCV‐2a ( P = .049) and HCV‐2b ( P = .02). The number of amino acid mutations was greater in complete responders than nonresponders in NS5A2193‐2228 (the region corresponding to the ISDR of HCV‐1b) alone ( P = .049), or NS5A2163‐2228 consisting of NS5A2193‐2228 plus its upstream region ( P = .02) in HCV‐2a, but not in HCV‐2b. A significant inverse correlation was observed between serum HCV‐RNA levels and the number of amino acid mutations in NS5A2193‐2228 ( P = .003) or NS5A2163‐2228 ( P = .005) in HCV‐2a. With multivariate analysis, the number of substitutions in NS5A was an independent predictor for complete response in HCV‐2a (odds ratio: 6.4; P = .03). Interferon efficacy is associated with amino acid variations in the NS5A protein in HCV‐2a infection.