Viral polymorphisms can affect the response to sofosbuvir in patients with chronic diseases.
Infections due to the hepatitis C virus (HCV), according to a study published in Gastroenterology.
is a pan-genotype inhibitor of HCV polymerase that eliminates most chronic HCV
Infections and substitutions badociated with polymerase resistance are rare.
However, studies have shown that genotype 3 of HCV is less sensitive to sofosbuvir.
that other HCV genotypes and previous interferon therapy have an impact on
answer. Therefore, the researchers collected data from National Health National England.
Early access program service to search for virus factors badociated with
Failure of treatment with sofosbuvir in 14 samples of genotype 3 of HCV. They identified
polymorphisms badociated with the reduced response and examined their effects by
Performing a multivariate logistic regression badysis in their badociation.
with sustained virological response in a separate cohort of 411 patients with
chronic infection with genotype 3 HCV that had been treated with sofosbuvir and
Ribavirin, with or without pegylated interferon. A common polymorphism, V in
position 150 in the genotype 3a NS5b of HCV polymerase, combined with other
It was found that the variants reduce the virus response to sofosbuvir. Thus,
clinically, HCV G3 infection containing this variant reduces the chances of
the authors concluded that, "For patients who have been exposed to multiple medications
regimens (including interferon and NS5a inhibitors that can lead to resistance
badociated polymorphisms) we speculate that the polymorphisms identified here
could be of importance and we suggest that viral sequencing before treatment can
be useful in selecting the optimal regimen for such patients. "However, later
Studies are needed in large cohorts of patients who are exposed to various
treatment regimens to identify patient cohorts that require virology
Analysis prior to therapy.
Ala PAC, Jones M, Cheung M, et al. The amino acid substitutions in the protein polymerase of the hepatitis C virus of genotype 3a affect the responses to sofosbuvir. Gastroenterology. doi: 10.1053 / j.gastro.2019.05.007
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