Key result
A higher median number of mutations in the PKR-binding domain of the HCV NS5A protein was associated with sustained or end-of-treatment virologic response to antiviral therapy.
Why the study?
Are mutations in the PKR-binding domain of the NS5A protein associated with treatment response to interferon-alpha in patients with HCV-1a?
Observational (n=32)
Are mutations in the PKR-binding domain of the NS5A protein associated with treatment response to interferon-alpha in patients with HCV-1a?
Mutations in the PKR-binding domain of the HCV NS5A protein are associated with a better virologic response to interferon-alpha therapy in patients with HCV-1a.
Answers are grounded in this paper and cite their sources.
Should not yet guide interferon use in HCV-1a; leaves open whether NS5A mutations predict response in modern DAA regimens.
An interaction of the hepatitis C virus (HCV) NS5A protein with the interferon (IFN)-alpha-inducible double-stranded RNA-activated protein kinase (PKR) was demonstrated in vitro. The clinical correlation between amino acid mutations within the HCV NS5A region and response to antiviral treatment is controversial. Thirty-two patients chronically infected with HCV-1a, who were treated with IFN-alpha with or without ribavirin, were studied. The carboxy-terminal half of HCV NS5A was sequenced and was investigated by phylogenetic and conformational analyses. Eight patients achieved a sustained virologic response. An end-of-treatment response but relapse thereafter was observed among 8 patients, whereas 16 patients were nonresponders. The median number of mutations within the PKR-binding domain but not within the previously described IFN sensitivity-determining region was significantly higher for patients with sustained (3 mutations [range, 1-5]) or end-of-treatment (4 mutations [range, 1-5]) virologic response than for nonresponders (2 mutations [range, 0-3]) (P=.0087). Phylogenetic and conformational analyses of NS5A sequences allowed no differentiation between sensitive and resistant strains.
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Sarrazin et al. (2000) conducted an observational in Chronic Hepatitis C Virus Type 1a infection (n=32). Mutations in the PKR-binding domain of the HCV NS5A protein vs. Fewer mutations was evaluated on Sustained or end-of-treatment virologic response (p=.0087). A higher median number of mutations in the PKR-binding domain of the HCV NS5A protein was associated with sustained or end-of-treatment virologic response to antiviral therapy.
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