Dataset Information

Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients.

ABSTRACT:

Background and objective

The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients.

Methods

Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B.

Results

In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4).

Conclusions

RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

SUBMITTER: Li Z

PROVIDER: S-EPMC5661091 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients.

Li Zhanyi Z Liu Ying Y Zhang Ying Y Shao Xiaoqiong X Luo Qiumin Q Guo Xiaoyan X Lin Guoli G Cai Qingxian Q Zhao Zhixin Z Chong Yutian Y

BioMed research international 20171015

<h4>Background and objective</h4>The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients.<h4>Methods</h4>Nested P ...[more]

PMID: 29164151

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Project description:It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk. We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA + IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.

Dataset Information

Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients.

Background and objective

Methods

Results

Conclusions

Publications

Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients.

Similar Datasets

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