Treatment of hepatitis C virus infection with direct‐acting antiviral agents: 100% cure?

Asselah, Tarik; Marcellin, Patrick; Schinazi, Raymond F.

doi:10.1111/liv.13673

Cited by 156 publications

(128 citation statements)

References 24 publications

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“…In response to the high burden of chronic hepatitis C virus (HCV) disease, the World Health Organization has set a goal of eliminating chronic HCV infection as a major global public health threat by 2030 . Well‐tolerated, simple, short‐duration, pan‐genotypic direct‐acting antiviral (DAA) regimens with high cure rates as measured by sustained virological response at post‐treatment week 12 (SVR12) will play an important role in realizing this goal . Adequate adherence to treatment is believed to be a key component of treatment success because non‐adherence can potentially result in treatment failure and the emergence of resistant viral variants…”

Section: Introductionmentioning

confidence: 99%

“…1 Well-tolerated, simple, short-duration, pan-genotypic directacting antiviral (DAA) regimens with high cure rates as measured by sustained virological response at post-treatment week 12 (SVR12) will play an important role in realizing this goal. [2][3][4] Adequate adherence to treatment is believed to be a key component of treatment success because non-adherence can potentially result in treatment failure and the emergence of resistant viral variants. 5 Previous analyses of DAA regimens have demonstrated high adherence to treatment in the overall chronic HCV-infected patient population, [6][7][8] including those who were on opioid substitution therapy (OST) and people who use drugs [9][10][11][12][13][14] (≥95% and ≥90% respectively).…”

Section: Introductionmentioning

confidence: 99%

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Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Brown

Welzel

Conway

et al. 2019

Liver International

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Background & Aims Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non‐adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non‐adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non‐adherence on sustained virological response at post‐treatment week 12 (SVR12) rates in HCV genotype (GT) 1‐6‐infected patients. Methods Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit. Exploratory logistic regression modelling assessed predictors of non‐adherence to G/P therapy. SVR12 rates by treatment adherence were assessed in the intent‐to‐treat (ITT) population and modified ITT (mITT) population, which excludes non‐virological failures. Results Overall, 97% (2024/2091) of patients were adherent to G/P therapy at all consecutive study visits. Alcohol use was the only baseline characteristic independently associated with non‐adherence to G/P therapy (OR: 2.38; 95% CI: 1.13‐5.01; P = .022). In the mITT population, overall SVR12 rates were high both in patients who were adherent to G/P therapy and those who were not (99% [1983/2008] and 95% [58/61] respectively; P = .047). Corresponding SVR12 rates in the ITT population were 98% (1983/2024) and 87% (58/67) respectively. Conclusions Most patients adhered to G/P therapy. SVR12 rates were high both in patients who were adherent to G/P treatment and those who were not. Patient education on treatment adherence should remain an important part of HCV treatment. Clinical trials registration NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, NCT02243293, NCT02446717.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Brown

Welzel

Conway

et al. 2019

Liver International

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“…NS5A inhibitors include velpatasvir, elbasvir, ledipasvir, daclatasvir, and ombitasvir. IFN‐free DAA combinations have revolutionized the area of HCV therapeutics, and 95% of patients with CHC have been reported to achieve end treatment response in contrast to which we have observed increasing rate of late HCV relapse even after DAA drug therapy …”

Section: Introductionmentioning

confidence: 65%

Prevalence of thyroid stimulating hormone dysfunction among sofosbuvir‐treated HCV‐infected patients: A real‐world clinical experience

Wahid

Waqar

Rasool

et al. 2018

Journal of Medical Virology

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Thyroid dysfunctions occur frequently among hepatitis C virus (HCV)-infected patients. Accumulating evidence has shown the higher incidence of thyroid dysfunctions in interferon-treated patients that was previously the standard of care therapy. However, the prevalence of thyroid disorders has not been studied in the recently developed interferon-free regimens or direct-acting antiviral (DAA) drugs-treated patients. We recruited 37 patients who had just completed 6 months long sofosbuvir-based treatment, and 26 interferon-treated patients were also included in the study. Serum thyrotropin level of all participants was measured using VIDAS. We observed thyroid dysfunctions in both pegylated interferon-experienced and DAA drug-experienced patients but the prevalence of hyperthyroidism was found significantly higher in patients treated with interferon-based regimen as compared with interferon-free regimens. This high prevalence of hypothyroidism in patients with HCV posttreatment highlights the need for regular periodic screening of patients during the treatment.

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“…The advent of the new interferon-free DAAs regimens has drastically changed the course of chronic hepatitis C infection, making it a curable disease for an impressive number of patients (>95%) (21). DAAs are targeted against NS3, NS5A, and NS5B viral proteins display different GB and, in some cases, can induce the selection of pre-existing resistance mutants (22).…”

Section: Discussionmentioning

confidence: 99%

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Dinu

Țârdei

Ceauşu

et al. 2018

Revista Romana De Medicina De Laborator

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Background: Severe complications of chronic hepatitis C -i.e. cirrhosis and hepatocellular carcinoma -are important causes of morbidity and mortality worldwide. Despite the overwhelming rates of sustained virologic response achieved after therapy with different combinations of direct-acting antiviral drugs (DAAs), treatment failure is still recorded, and is due to the mutations harboured by hepatitis C virus (HCV) resistance associated variants (RAVs) selected during therapy. Baseline RAVs testing was found significant for guiding treatment in the cases of treatment failure and, sometimes, in naïve patients.Methods: Romanian chronic hepatitis C patients unexposed to DAAs and infected with subtype 1b HCV were studied. Serum samples were used for Sanger population sequencing of a fragment containing NS3 viral protease, known to harbour resistance mutation against protease inhibitors (PIs).Results: Catalytic triad and zinc-binding site in the studied sequences were conserved. Low-intermediate resistance mutations to first generation PIs were detected either alone or in conjunction with resistance substitutions associated with second generation PIs. Cross-resistance and reduced susceptibility to certain DAAs were observed.Discussion: This study focused on HCV patients infected with subtype 1b strains, the most prevalent in Romania. The rate of RAVs found in this work is consistent with the results reported by similar studies from other countries. Noticeably, numerous polymorphisms of unknown significance to DAAs resistance, but reflecting the

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Treatment of hepatitis C virus infection with direct‐acting antiviral agents: 100% cure?

Cited by 156 publications

References 24 publications

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Adherence to pan‐genotypic glecaprevir/pibrentasvir and efficacy in HCV‐infected patients: A pooled analysis of clinical trials

Prevalence of thyroid stimulating hormone dysfunction among sofosbuvir‐treated HCV‐infected patients: A real‐world clinical experience

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

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