Global epidemiology of HCV subtypes and resistance-associated substitutions evaluated by sequencing-based subtype analyses

Welzel, Tania M.; Bhardwaj, Neeru; Hedskog, Charlotte; Chodavarapu, Krishna; Camus, Grégory; McNally, John; Brainard, Diana M.; Miller, Michael D.; Mo, Hongmei; Svarovskaia, Evguenia S.; Jacobson, Ira M.; Zeuzem, Stefan; Agarwal, Kosh

doi:10.1016/j.jhep.2017.03.014

Cited by 119 publications

(147 citation statements)

References 40 publications

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“…In the present study, both patients with treatment failure had NS5A L31 M, but not NS5B RASs at baseline. However, RAS analysis showed that almost all patients (94–97%) with subtype 2a and 39–89% of those with subtype 2b originally had NS5A L31 M at baseline . In addition, the SVR rate for patients with NS5A RASs was extremely high (97.6%, 165/169) in clinical trials .…”

Section: Discussionmentioning

confidence: 99%

Ledipasvir and sofosbuvir for 12 weeks for hepatitis C virus genotype 2 infection: A propensity score matched analysis

Ogawa

Nomura

Nakamuta

et al. 2019

Hepatology Research

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Aim Hepatitis C virus genotype 2 is common in East Asia, sub‐Saharan Africa, and Latin America. However, many countries in these areas lag behind other areas of the world in government approval for new direct‐acting antivirals. The aim of this study was to evaluate the treatment outcome of ledipasvir/sofosbuvir (LDV/SOF) for patients with chronic hepatitis C virus genotype 2 infection. Methods This is a two‐part multicenter, real‐world cohort study. Study 1 consisted of 58 consecutive patients who were treated with LDV/SOF for 12 weeks. Study 2 used propensity score matching for LDV/SOF (n = 58) and glecaprevir/pibrentasvir (n = 207) treatment groups (1:1) with a set of clinically important variables. Sustained viral response 12 weeks after the end of treatment (SVR12) and adverse events were evaluated in both studies. Results In study 1, the overall SVR12 rates of the intention‐to‐treat and modified intention‐to‐treat populations were 94.8% (55/58) and 96.5% (55/57), respectively. High SVR12 rates were observed in almost all subgroups, including older age, compensated cirrhosis, and treatment experience. In study 2, propensity score matching of the entire study population yielded 52 matched pairs with similar baseline characteristics. There were no statistically significant differences between the LDV/SOF (96.1%) and glecaprevir/pibrentasvir (98.0%) groups in the overall SVR12 rates of the modified intention‐to‐treat populations, and their rates of treatment discontinuation and adverse events were similar. Conclusions Treatment with LDV/SOF for hepatitis C virus genotype 2 resulted in a high rate of SVR12 and excellent tolerability. The outcomes of LDV/SOF were very similar to those of glecaprevir/pibrentasvir.

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Section: Discussionmentioning

confidence: 99%

Ledipasvir and sofosbuvir for 12 weeks for hepatitis C virus genotype 2 infection: A propensity score matched analysis

Ogawa

Nomura

Nakamuta

et al. 2019

Hepatology Research

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“…While the SVR12 rate for non‐4a, non‐4d GT4 subtypes was numerically lower, virologic failures in this group occurred only among participants with one of two uncommon subtypes, 4b and 4r. Extensive HCV genetic variability exists at multiple key NS5A resistance‐associated amino acid positions, both across and within different HCV subtypes . Recent studies have shown that reduced susceptibility to ledipasvir for some GT 4b and 4r isolates is associated with the presence of NS5A resistance‐associated substitutions, which may explain occurrences of ledipasvir/sofosbuvir virologic failure among patients with these subtypes .…”

Section: Discussionmentioning

confidence: 99%

HCV genotype 4, 5 and 6: Distribution of viral subtypes and sustained virologic response rates in clinical trials of approved direct‐acting antiviral regimens

Boyd

Harrington

Komatsu

et al. 2018

Journal of Viral Hepatitis

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Multiple direct-acting antiviral (DAA)-based regimens are now available for all hepatitis C virus (HCV) genotypes (GTs). Because HCV GT 4, 5 and 6 are less common in the United States (US) and worldwide, relatively small numbers of participants with these GTs were evaluated in individual clinical trials. To provide a comprehensive description of subtype diversity and treatment outcomes in clinical trials for these less common GTs, we analysed data from 744 participants with HCV GT4 (n = 573), GT5 (n = 81), or GT6 (n = 90) across 18 clinical trials of DAA regimens. These data are from US New Drug Applications submitted between 2014 and 2017, and our analyses included only approved regimens. Excluding unresolved or mixed subtypes, the distribution of reported GT4 subtypes was 49% 4a, 31% 4d and 16% for one of 14 other subtypes. The distribution of GT6 subtypes was 39% 6a, 27% 6e, 8% 6 L and 23% for one of 11 other subtypes. Across approved regimens, sustained virologic response rates 12 weeks post-treatment (SVR12) for GT 4, 5 and 6 ranged from 91% to 100%, 93% to 97% and 96% to 100%, respectively. SVR12 by GT4 subtype ranged from 96% to 100% for 4a and 81% to 100% for 4d. Virologic failures occurred in GT 4a, 4b, 4d and 4r. For GT6, SVR12 was 100% for all subtypes except 6 L, for which 1 of 7 participants experienced virologic failure. To our knowledge, this is the largest compilation of HCV GT 4, 5 or 6 clinical trial data. These analyses may be useful for clinicians treating HCV GT 4, 5 or 6.

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“…The frequency of naturally occurring G1 NS3-resistant variants has been reported to range between 0.1 and 3.1%, with the exception of the Q80K variant that has a good replicative fitness and is present from 19 to 48% of isolates belonging to clade I of HCV G1a, which is reported to be typically diffused in North America [5,6,[8][9][10].…”

Section: Hepatitis C Virus (Hcv) Infection Ismentioning

confidence: 99%

NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Naïve Patients with Chronic Hepatitis C

D’Aliberti

Cacciola²,

Musolino³

et al. 2018

Intervirology

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Background: Hepatitis C virus (HCV) NS3 resistance-associated substitutions (RASs) reduce HCV susceptibility to protease inhibitors. Little is known about NS3 RASs in viral isolates from the liver of chronic hepatitis C (CHC) patients infected with HCV genotype-1a (G1a). Aim: The objective of this work was to study NS3 variability in isolates from the serum and liver of HCV-G1a-infected patients naïve to direct-acting antivirals (DAAs). Methods: NS3 variability of HCV-G1a isolates from the serum and liver of 11 naïve CHC patients, and from sera of an additional 20 naïve CHC patients, was investigated by next-generation sequencing. Results: At a cutoff of 1%, NS3 RASs were detected in all the samples examined. At a cutoff of 15%, they were found in 54.5% (6/11) and 27.3% (3/11) of the paired liver and serum samples, respectively, and in 22.5% (7/31) of the overall serum samples examined. Twenty-six out of thirty-one (84%) patients showed NS3 variants with multiple RASs. Phylogenetic analysis showed that NS3 sequences clustered within 2 clades, with 10/31 (32.2%) patients infected by clade I, 15/31 (48.8%) by clade II, and 6/31 (19.3%) by both clades. Conclusions: Though the number of patients examined was limited, NS3 variants with RASs appear to be major components of both intrahepatic and circulating viral quasispecies populations in DAA-naïve patients.

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Global epidemiology of HCV subtypes and resistance-associated substitutions evaluated by sequencing-based subtype analyses

Cited by 119 publications

References 40 publications

Ledipasvir and sofosbuvir for 12 weeks for hepatitis C virus genotype 2 infection: A propensity score matched analysis

Ledipasvir and sofosbuvir for 12 weeks for hepatitis C virus genotype 2 infection: A propensity score matched analysis

HCV genotype 4, 5 and 6: Distribution of viral subtypes and sustained virologic response rates in clinical trials of approved direct‐acting antiviral regimens

NS3 Variability in Hepatitis C Virus Genotype 1A Isolates from Liver Tissue and Serum Samples of Treatment-Naïve Patients with Chronic Hepatitis C

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