Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir

Younossi, Zobair M.; Stepanova, Maria; Gordon, Stuart C.; Zeuzem, Stefan; Mann, Michael P.; Jacobson, Ira M.; Bourlière, Marc; Cooper, Curtis; Flamm, Steven L.; Reddy, K. Rajender; Kowdley, Kris V.; Younossi, Issah; Hunt, Sharon

doi:10.1016/j.cgh.2017.11.023

Cited by 25 publications

(35 citation statements)

References 43 publications

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“…In this study, we used the PRO data collected from participants of a deferred treatment substudy of POLARIS‐1, a multicentre multinational phase 3 placebo‐controlled clinical trial of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in direct‐acting antiviral (DAA)‐experienced patients (clinicaltrials.gov #NCT02607735) . Originally, in POLARIS‐1, patients were randomized in a blinded manner to receive either a fixed‐dose combination of SOF/VEL/VOX or placebo once daily for 12 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Originally, in POLARIS‐1, patients were randomized in a blinded manner to receive either a fixed‐dose combination of SOF/VEL/VOX or placebo once daily for 12 weeks. Then, for the deferred treatment substudy, patients who had completed treatment with placebo received open‐label therapy with SOF/VEL/VOX for 12 weeks, the treatment must have started within 60 days of unblinding in the primary study which was post‐treatment week 4 after cessation of treatment with placebo …”

Section: Methodsmentioning

confidence: 99%

“…The trial was conducted in the United States, Canada, Australia, New Zealand, Germany, France and Great Britain in 2015‐2017. The safety and efficacy outcomes of POLARIS‐1, as well as PRO results of the primary study, have been published …”

Section: Methodsmentioning

confidence: 99%

“…Patient‐reported outcomes were collected prospectively using 4 self‐administered PRO instruments: the Short‐Form‐36 (SF‐36), the Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F), the Chronic Liver Disease Questionnaire‐HCV Version (CLDQ‐HCV), and the Work Productivity Activity Index: Specific Health Problem (WPAI:SHP) at baseline (the first day of active treatment), at treatment weeks 4 and 12, and at week 4, 12, and 24 follow‐up visits. Together, these 4 PRO instruments return 26 scores which include individual HRQL domains (such as physical functioning, fatigue, or emotional well‐being), the instruments’ summary scores, and one preference‐based utility score (SF‐6D), all calculated as described before . In all PRO domains, greater scores reflect better health status except for the domains of WPAI:SHP in which greater scores indicate more impairment.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Viral eradication is required for sustained improvement of patient‐reported outcomes in patients with hepatitis C

Younossi

Stepanova

Reddy

et al. 2018

Liver International

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Viral eradication is required for sustained improvement of patient‐reported outcomes in patients with hepatitis C

Younossi

Stepanova

Reddy

et al. 2018

Liver International

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“…The introduction of well‐tolerated second generation DAAs has subsequently shown excellent SVR rates and improvement in HRQOL scores post‐SVR . These studies have also suggested that interferon‐free regimens lead to improvement in PROs which are sustained after achieving SVR …”

Section: Introductionmentioning

confidence: 98%

Cytokine balance is restored as patient‐reported outcomes improve in patients recovering from chronic hepatitis C

Avila

Weinstein

Estep

et al. 2019

Liver International

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Background & Aims Chronic hepatitis C (CHC) has a negative impact on patient‐reported outcomes (PROs). Although most CHC patients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHC patients who achieve SVR. Methods Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed‐dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form‐36 (SF‐36), Fatigue Severity Scale (FSS), Beck Depression Inventory‐II (BDI‐II), Chronic Liver Disease Questionnaire‐HCV (CLDQ‐HCV) and Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow‐up week 24. Results Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF‐36 physical health summary score (rho = −0.34, P < 0.05), SF‐36 physical functioning (rho = −0.34, P < 0.05), SF‐36 bodily pain (rho = −0.39, P < 0.05) and FACIT‐F physical well‐being (rho = −0.54, P < 0.001). Changes in emotional well‐being (FACIT‐F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = −0.4, P = 0.01, and rho = −0.35, P < 0.05 respectively). Conclusions These data indicate relationships between PROs and serum biomarkers pre‐ and post‐SVR in CHC. These concomitant changes may have important clinical relevance.

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Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

et al. 2019

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The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion : Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.

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Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir

Cited by 25 publications

References 43 publications

Viral eradication is required for sustained improvement of patient‐reported outcomes in patients with hepatitis C

Viral eradication is required for sustained improvement of patient‐reported outcomes in patients with hepatitis C

Cytokine balance is restored as patient‐reported outcomes improve in patients recovering from chronic hepatitis C

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

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