当前位置： SCI文献检索 > ANTIVIRAL THERAPY期刊下所有文献 > Meta-analysis of mutations in the NS5A gene and hepatitis C virus resistance to interferon therapy: uniting discordant conclusions.

Meta-analysis of mutations in the NS5A gene and hepatitis C virus resistance to interferon therapy: uniting discordant conclusions.

Abstract：

BACKGROUND:Hepatitis C virus genotype 1B responds poorly to treatment with interferon, in contrast to the more interferon-sensitive genotypes 2 and 3. Studies on combination therapy regimens with PEG-interferon and ribavirin report sustained response rates that generally do not exceed 50%, in contrast to sustained response rates of 80% for genotype 2 and 3. In Japan, a correlation was found between the number of mutations in an 'interferon sensitivity determining region' (ISDR) and outcome of interferon treatment in genotype 1B-infected patients. However, an ongoing controversy on the existence of an ISDR in non-Japanese isolates resulted, as non-Japanese studies failed to confirm this association. The present study approached this issue by carrying out a meta-analysis of ISDR sequences and response to interferon treatment. METHODS:Twenty-seven studies were included, reporting 1351 ISDR sequence data of genotype 1B-infected patients and their virological response to interferon treatment. Both summary statistics and individual patient data were used systematically to explore the association between ISDR mutations and response to interferon. RESULTS:The ISDR effect on response was universally present but appeared to be stronger in Japan, with a relative risk of 5.73 for mutant viruses as compared to 4.66 for non-Japanese isolates. High interferon dose, in Japan administered more frequently, was associated with an increase in response rate only among patients infected with mutant isolates. Interaction between dose and ISDR type was confirmed in a logistic regression model. After stratifying for dose, differences in response rate between Japanese and non-Japanese patients were no longer present. CONCLUSION:This study puts an end to a longstanding controversy by confirming the universal existence of an ISDR in genotype 1B-infected patients. Apparent discrepant findings from Japanese and non-Japanese studies can be explained by differences in dosing regimens and a dose-dependent differential effect of ISDR mutations on response to treatment.

journal_name

Antivir Ther

journal_title

Antiviral therapy

authors

Schinkel J,Spaan WJ,Kroes AC

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

275-86

issue

eissn

1359-6535

issn

2040-2058

journal_volume

pub_type

杂志文章,meta分析

在线工具

Meta-analysis of mutations in the NS5A gene and hepatitis C virus resistance to interferon therapy: uniting discordant conclusions.