Dataset Information

Genotyping of HBV and tracking of resistance mutations in treatment-naive patients with chronic hepatitis B.

ABSTRACT: BACKGROUND AND AIMS:Resistance mutation analogs to nucleos(t)ides have been described in treatment-naïve patients with chronic hepatitis B (CHB), with clinical implications. The aim of this study was to investigate primary resistance mutations and genotypes circulating in patients naïve to chronic hepatitis B, in the Northern and Northeastern regions of Brazil. METHODS:We conducted a study of resistance mutations and genotypic characterization of hepatitis B virus (HBV) in 189 treatment-naïve patients chronically infected with HBV. RESULTS:Drug resistance-associated mutations located in the RT domain of the P gene (rtHBV) were found in 6% of the treatment-naïve patients from the Northeastern Region. The mutations were rtA194T, rtL180M + rtM204V, rtS202I, rtM204I, and rtA181S. No patient in the Northern Region had the resistance mutation. In the gene S region, the frequency of vaccine escape mutations was 2.4% in the Northeastern Region and 8.6% in the Northern Region. CONCLUSION:This information before the start of treatment may contribute to clinical decision making, reducing treatment failure and the risk of progression to cirrhosis and hepatocellular carcinoma for CHB.

SUBMITTER: Pacheco SR

PROVIDER: S-EPMC5503499 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Genotyping of HBV and tracking of resistance mutations in treatment-naïve patients with chronic hepatitis B.

Pacheco Sidelcina Rugieri SR Dos Santos Maria Isabel Magalhães Andrade MIMA Stocker Andreas A Zarife Maria Alice Sant'Anna MAS Schinoni Maria Isabel MI Paraná Raymundo R Dos Reis Mitermayer Galvão MG Silva Luciano Kalabric LK

Infection and drug resistance 20170705

<h4>Background and aims</h4>Resistance mutation analogs to nucleos(t)ides have been described in treatment-naïve patients with chronic hepatitis B (CHB), with clinical implications. The aim of this study was to investigate primary resistance mutations and genotypes circulating in patients naïve to chronic hepatitis B, in the Northern and Northeastern regions of Brazil.<h4>Methods</h4>We conducted a study of resistance mutations and genotypic characterization of hepatitis B virus (HBV) in 189 tre ...[more]

PMID: 28740410

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Project description:IntroductionTreatment of HCV infection with peginterferon and ribavirin results in a low sustained virologic response rate, but has a number of undesirable adverse effects. Direct-acting antivirals (DAAs) offer a high efficacy, low risk, and a short treatment time. However, the existence of resistance-associated mutations, particularly in the NS5B polymerase, can attenuate the efficacy of DAAs. The objective of this study was to identify amino acid changes in the NS5B gene linked to DAA resistance in treatment-naive Vietnamese chronic hepatitis C patients.MethodsBlood samples and treatment data were collected from 100 HCV-infected patients hospitalized at the National Hospital for Tropical Diseases between January and December 2020; the plasma was then isolated and stored at -80°C for molecular analysis. The NS5B gene fragments of 100 samples were amplified with specified primers and the nucleotide sequences were obtained using the Sanger sequencing system. The nucleotide sequences were then analyzed and compared to identify substitutions in the NS5B region.ResultsA total of 100 HCV isolates from patients were classified into three genotypes, including genotypes 1, 3, and 6. The NS5B sequence analysis revealed many amino acid mutations in all genotypes, although these mutations were not strongly associated with resistance to DAAs like S282T. Analytical data on ribavirin-resistance mutations revealed that Q309R was predominantly found in genotype 1a, D310N was mostly found in genotype 1b, and N244I, T329I, A333E were not observed. The following mutations were shown to be related with DAAs resistance: E237G, S282R, L320F, V321A, and V321I. Furthermore, NS5B-resistance mutations were not associated with clinical characteristics, long-term virological response, or improvements in clinical parameters (liver enzymes or liver fibrosis index).ConclusionAlthough NS5B mutations were found in treatment-naive Vietnamese patients, changes in the NS5B gene did not appear to be highly correlated with HCV ribavirin and DAA antiviral resistance.

Project description:Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication-competent, drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multidrug resistance. Collectively, however, 8.6% of the patients infected with genotype 1a and 1.4% of those infected with genotype 1b carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses in vivo.Naturally occurring dominant STAT-C resistance mutations are common in treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin.

Dataset Information

Genotyping of HBV and tracking of resistance mutations in treatment-naive patients with chronic hepatitis B.

Publications

Genotyping of HBV and tracking of resistance mutations in treatment-naïve patients with chronic hepatitis B.

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