Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Guangzhou, China: Predominance of Genotype 1b and Increasing Incidence of Genotype 6a

Yuan, Guosheng; Liu, Jun-Wei; Hu, Chengguang; Huang, Huaping; Qi, Minghua; Wu, Tao; Liang, Weifang; Li, Yi-Ping; Zhang, Yongyuan; Zhou, Yuanping

doi:10.1159/000481561

Cited by 14 publications

(12 citation statements)

References 33 publications

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“…Phylogenetic analyses based on HCV structure protein sequences concerning HCV isolates circulating in China have been reported previously, mainly on GT1b and GT6a sequences (Nakano et al, 2006; Fu et al, 2011, 2012; Yuan et al, 2017). The sizeable number of GT3a and GT3b NS5A sequences determined in this study gave us an opportunity to have a close look at the phylogenetic relationship between these domestic GT3 sequences and reference sequences deposited in public database.…”

Section: Resultsmentioning

confidence: 99%

Subtype-Specific Prevalence of Hepatitis C Virus NS5A Resistance Associated Substitutions in Mainland China

Feng

Chen

et al. 2019

Front. Microbiol.

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Resistance associated substitutions (RASs) can reduce the efficacy of direct-acting antiviral agents (DAAs) targeting hepatitis C virus (HCV) and lead to treatment failure. Clinical data of HCV NS5A RASs prevalence are limited in China and need to be investigated. A total of 878 unique patient samples with different genotypes (GT) (1b: n = 489, 2a: n = 203, 3a: n = 60, 3b: n = 78, 6a: n = 48) were collected from around mainland China by KingMed Laboratory and analyzed for NS5A RASs distribution by Sanger sequencing. Phylogeographic analyses based on NS5A domain 1 sequences indicated circulation of both locally and nationally epidemic strains. Relatively high frequency of Y93H (14.1%) was only detected in GT1b but not in other subtypes. High frequency of L31M was found in both GT2a (95.6%) and GT3b (98.7%) sequences. Due to the overlapping incidence of A30K, 96% of GT3b isolates had NS5A RASs combination A30K + L31M, which confers high levels of resistance to most NS5A inhibitors. No RASs were detected in GT6a strains. Meanwhile, baseline NS5A RASs fingerprints were also evaluated in 185 DAA treatment-naive GT1b patients with next generation sequencing method. Patients presenting with Y93H had statistically higher entropy of HCV NS5A sequences. Taken together, subtype-specific distribution patterns of NS5A RASs were observed. GT1b patients with higher HCV complexity tend to have a greater chance of Y93H presence, while GT3b patients are naturally resistant to current NS5A inhibitors and their treatment may pose a challenge to real-world DAA application.

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Section: Resultsmentioning

confidence: 99%

Subtype-Specific Prevalence of Hepatitis C Virus NS5A Resistance Associated Substitutions in Mainland China

Feng

Chen

et al. 2019

Front. Microbiol.

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“…The current recommendations for GT6 from the guidelines are based on small number of patients in clinical trials [ 14 , 15 ]. In addition, different from other provinces, GT6a accounts for about 20.2% and 35.0% in Guangdong province and Hainan province (the two main study centers of this study), respectively [ 16 , 17 ]. An important finding in this study was that the SOF-based regimens in patients infected with HCV GT 6a were as effective as those infected with GT 1b, and SVR12 was achieved by 98% and 100% in GT 1b and 6a patients (P=0.322), respectively.…”

Section: Discussionmentioning

confidence: 99%

Sofosbuvir-Based Therapies for Patients with Hepatitis C Virus Infection: Real-World Experience in China

Yuan

Liu

et al. 2018

Canadian Journal of Gastroenterology and Hepatology

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Background and Aims There is scarcity of data in literature regarding the treatment response to sofosbuvir- (SOF-) based therapies in Chinese patients with chronic Hepatitis C Virus (HCV) infection. The aim of this study was to evaluate the efficacy and safety of SOF-based regimens for chronic hepatitis C (CHC) patients without cirrhosis in a real-world setting in mainland China. Methods A total of 226 patients receiving SOF plus daclatasvir (DCV), ledipasvir (LDV), or velpatasvir (VEL) were enrolled from December 2014 to June 2017. The primary observation point was the percentage of patients with a sustained virologic response (SVR) at posttreatment week 12 (SVR12), and all adverse events were monitored during treatment and follow-up period. Results The overall SVR12 rate was 96% (216/226), and individual SVR12 ranged from 93% to 100% in different treatment groups. No significant differences of efficacy were detected between genotypes 1b and 6a (98% for GT 1b versus 100% for GT 6a, P=0.322). Comparing the high success rates in GT 1b and 6a patients, SVR12 was relatively low in GT 3a and 3b patients. A significant difference in efficacy was observed between GT 3 and not GT 3 patients (77% versus 98%, respectively, P<0.001). No significant differences in efficacy were detected among different regimens (93% versus 97% versus 100%, respectively, P=0.153), gender (95% for male versus 96% for female, P=0.655), or baseline HCV RNA lever (96% versus 95%, respectively, P=0.614). Similar SVR rates were also obtained in naïve and previously treated patients (98% versus 93%, respectively, P=0.100). Conclusions NS5B polymerase inhibitor SOF plus one of the NS5A inhibitors, such as DCV, LDV, or VEL for 12 weeks was associated with high SVR12 rates and well tolerated in HCV-infected patients without cirrhosis. Moreover, patients with DAAs failure should be retreated with more effective regimens like SOF/VEL.

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“…The high prevalence of genotype 3, which is considered difficult to cure, remains a challenge because many oral DAAs are less effective for this genotype, particularly subtype 3b than for others . The current guidance generally recommends sofosbuvir (SOF)/velpatasvir (VEL)±ribavirin (RBV), glecaprevir/pibrentasvir, and SOF/VEL/voxilaprevir as first‐line therapy for genotype 3, and an interferon‐based regimen—SOF plus pegylated interferon and RBV—is still recommended as an alternative treatment option . These recommendations are based on clinical data generated in regions where genotype 3a predominates.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the efficacy of sofosbuvir plus ribavirin in Chinese patients with genotype 3a or 3b HCV infection

Huang

Rao

Xie

et al. 2019

Journal of Medical Virology

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Background and Aim: Genotype 3b hepatitis C virus (HCV) infection represents approximately 50% of patients with genotype 3 in China. We compared the efficacy of sofosbuvir (SOF) plus ribavirin (RBV) in Chinese patients with genotype 3a and 3b HCV. Methods: The analyzed data are from a phase 3, open-label study of SOF plus RBV for 24 weeks conducted in China. The primary endpoint for the trial was sustained virologic response at 12 weeks after the end of therapy (SVR12).Results: Of 126 patients included in this analysis, 58 (46%) had genotype 3a and 68 (54%) had genotype 3b. Both the subtypes were similar in age, sex, body mass index, IL28B, and baseline HCV RNA. However, more treatment-experienced and cirrhotic patients were in the genotype 3b group. All 100% of patients with genotype 3a (95% confidence interval [CI], 94-100), and 91% (95% CI, 82-97) of patients with genotype 3b achieved SVR12 (P = 0.030). For treatment-experienced patients with genotype 3b, the SVR12 rate was 73% (95% CI, 39-94) and 88% (95% CI, 64-99) among patients with and without cirrhosis (P = 1.00), respectively.Conclusion: SOF plus RBV for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of SVR. However, the SVR12 rate among patients with genotype 3b was lower than that observed in patients with genotype 3a infection, particularly among treatment-experienced patients with cirrhosis.

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Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Guangzhou, China: Predominance of Genotype 1b and Increasing Incidence of Genotype 6a

Cited by 14 publications

References 33 publications

Subtype-Specific Prevalence of Hepatitis C Virus NS5A Resistance Associated Substitutions in Mainland China

Subtype-Specific Prevalence of Hepatitis C Virus NS5A Resistance Associated Substitutions in Mainland China

Sofosbuvir-Based Therapies for Patients with Hepatitis C Virus Infection: Real-World Experience in China

Comparison of the efficacy of sofosbuvir plus ribavirin in Chinese patients with genotype 3a or 3b HCV infection

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