Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-epidemic HCV genotypes in low- and middle-income countries and the risk of resistance to current direct-acting antiviral regimens.

ABSTRACT: The hepatitis C virus (HCV) is an extremely diverse virus, subtypes of which are distributed variably around the world. Viral genotypes may be divided into epidemic subtypes; those that have become prevalent globally, and endemic subtypes that have a more limited distribution, mainly in Africa and Asia. The high variability of endemic strains reflects evolutionary origins in the locations where they are found. This increased genetic diversity raises the possibility of resistance to pan-genotypic direct-acting antiviral regimens. While many endemic subtypes respond well to direct-acting antiviral therapies, others, for example genotypes 1l, 3b and 4r, do not respond as well as predicted. Many genotypes that are rare in high-income countries but common in other parts of the world have not yet been fully assessed in clinical trials. Further sequencing and clinical studies in sub-Saharan Africa and Asia are indicated to monitor response to treatment and to facilitate the World Health Organization's 2030 elimination strategy.

SUBMITTER: Shah R

PROVIDER: S-EPMC8310923 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study.

Project description:BackgroundThe majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands.MethodsWe performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation.ResultsWe included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3-infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS.ConclusionsThe DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.

| S-EPMC7881754 | biostudies-literature

Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV-TARGET study.

Project description:Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2.ConclusionIn a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

| S-EPMC5756478 | biostudies-literature

Direct-Acting Antiviral Agents for HCV Infection.

Project description: Not available

| S-EPMC5938327 | biostudies-literature

Early View of the Effectiveness of New Direct-Acting Antiviral (DAA) Regimens in Patients with Hepatitis C Virus (HCV).

Project description:IntroductionClinical trials have demonstrated the efficacy of all-oral direct-acting antiviral (DAA) regimens in the treatment of patients infected with hepatitis C virus (HCV). This study assessed real-world effectiveness of two recently approved regimens; paritaprevir/ritonavir/ombitasvir; dasabuvir (3D), and sofosbuvir/ledipasvir (SOF/LDV) in patients with HCV genotype 1.MethodsA retrospective analysis of administrative claims data (IMS Health Patient-Centric Data Warehouse/Medivo database) from October 1, 2013 to August 14, 2015 was conducted. Patients ≥19 years of age with a HCV genotype 1 infection, a prescription fill for 3D or SOF/LDV, and ≥1 HCV viral load (VL) assessment from weeks 4-30 post-treatment were selected for analysis. Percentages of patients achieving sustained virologic response (SVR; defined as HCV RNA ≤43 IU/mL) were determined. Unadjusted SVR rates were compared between treatment groups using Fisher's exact tests. SVR rates were also assessed using multivariate regression with adjustment for age group, sex, and treatment history. Analyses were repeated for a subset of patients with VL assessment from 12 to 30 weeks post-treatment.ResultsA total of 1707 (44 3D and 1663 SOF/LDV) patients were included. The majority (60%) were male, 49% were aged 55-64 years, and 97% were treatment-naïve 1 year prior to index. The unadjusted relative risk (RR) for achieving SVR in patients treated with SOF/LDV compared with 3D was 0.98%, 95% confidence interval (CI): 0.93-1.02. After adjusting for the baseline covariates, the RR was 0.98%, 95% CI: 0.94-1.03.ConclusionsIn this early view of real-world data, effectiveness of all-oral DAA regimens in HCV genotype 1 patients was concordant with results from registration trials. SVR rates were similar for the two regimens. Further studies are needed to confirm these results.FundingAbbVie, Inc.

| S-EPMC4662718 | biostudies-literature

Retreatment Options Following HCV Direct Acting Antiviral Failure.

Project description:Despite the excellent efficacy of direct acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment approaches previously depended on limited clinical trials and expert opinion. In this article, we review the current state of the evidence for HCV retreatment after DAA failure. Based on recent clinical trial data, most patients who fail HCV treatment with DAA agents now have excellent retreatment options. While some patients may benefit from resistance testing after DAA therapy failure to select the optimal treatment and duration, newly approved salvage therapies are not significantly impacted by common mutations and have been approved by the Food and Drug Administration for HCV retreatment without regard for the presence of resistance associated substitutions. While prior retreatment efforts were limited to longer courses of therapy, the addition of ribavirin, or novel combinations of approved therapies based on expert guidance, current DAA options make HCV retreatment in the DAA era more streamlined and evidence-based.

| S-EPMC5726279 | biostudies-literature

Measuring Quality in Colorectal Cancer Surgery in Low- and Middle-income Countries

Project description:To test the applicability of the Clavien-Dindo Classification (CDC) in an LMIC setting and to compare the prevalence and severity of complications in patients <60 and ≥60 years of age a retrospective medical records review is used.

| 2400292 | ecrin-mdr-crc

Perceptions and impact of plain packaging of tobacco products in low and middle income countries, middle to upper income countries and low-income settings in high-income countries: a systematic review of the literature.

Project description:To review the current literature around the potential impact, effectiveness and perceptions of plain packaging in low income settings.A systematic review of the literature.9 databases (PubMed, Global Health, Social Policy and Practice, Applied Social Sciences Index and Abstracts (ASSIA), CINAHL, PsycINFO, British Library for Development Studies (BLDS), Global Health Library and Scopus) were searched. The terms used for searching combined terms for smoking and tobacco use with terms for plain packaging.Studies investigating the impact of plain packaging on the determinants of tobacco use, such as smoking behaviour, appeal, prominence, effectiveness of health warnings, response to plain packs, attitudes towards quitting or likelihood of smoking in low-income settings, were identified. Studies must have been published in English and be original research of any level of rigour.Two independent reviewers assessed studies for inclusion and extracted data.The results were synthesised qualitatively, with themes grouped under four key headings: appeal and attractiveness; salience of health warnings and perceptions of harm; enjoyment and perceived taste ratings; and perceptions of the impact on tobacco usage behaviour.This review has identified four articles that met the inclusion criteria. Studies identified that tobacco products in plain packaging had less appeal than in branded packaging in low-income settings.This review indicates that plain packaging appears to be successful in reducing appeal of smoking and packets, and supports the call for plain packaging to be widely implemented in conjunction with other tobacco control policies. However, there are considerable gaps in the amount of research conducted outside high-income countries.

| S-EPMC4809104 | biostudies-other

Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens.

Project description:BackgroundThe optimal retreatment strategy for chronic hepatitis C virus (HCV) patients who fail directly-acting antiviral agent (DAA)-based treatment is unknown. In this study, we assessed the efficacy and safety of ledipasvir (LDV) and sofosbuvir (SOF) for 12 weeks in HCV genotype-1 (GT-1) patients who failed LDV/SOF-containing therapy.MethodsIn this single-center, open-label, phase 2a trial, 34 participants with HCV (GT-1) and early-stage liver fibrosis who previously failed 4-6 weeks of LDV/SOF with GS-9669 and/or GS-9451 received LDV/SOF for 12 weeks. The primary endpoint was HCV viral load below the lower limit of quantification 12 weeks after completion of therapy (sustained virological response [SVR]12). Deep sequencing of the NS3, NS5A, and NS5B regions were performed at baseline, at initial relapse, prior to retreatment, and at second relapse with Illumina next-generation sequencing technology.ResultsThirty-two of 34 enrolled participants completed therapy. Two patients withdrew after day 0. Participants were predominantly male and black, with median baseline HCV viral load of 1.3 × 10(6) IU/mL and Metavir fibrosis stage 1 and genotype-1a. Median time from relapse to retreatment was 22 weeks. Prior to retreatment, 29 patients (85%) had NS5A-resistant variants. The SVR12 rate was 91% (31/34; intention to treat, ITT) after retreatment. One patient relapsed.ConclusionsIn patients who previously failed short-course combination DAA therapy, we demonstrate a high SVR rate in response to 12 weeks of LDV/SOF, even for patients with NS5A resistance-associated variants.Clinical trials registrationNCT01805882.

| S-EPMC4706633 | biostudies-literature

Hypertension in Low- and Middle-Income Countries.

Project description:In recent decades low- and middle-income countries (LMICs) have been witnessing a significant shift toward raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers, and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity, tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.

| S-EPMC8091106 | biostudies-literature

Disparities in Unintentional Occupational Injury Mortality between High-Income Countries and Low- and Middle-Income Countries: 1990?2016.

Project description:OBJECTIVE:Using estimates from the Global Burden of Disease (GBD) study, we examined differences in unintentional occupational injury mortality rates from 1990 to 2016 between high-income countries (HICs) and low- and middle-income countries (LMICs). METHODS:Unintentional occupational injury mortality rates were obtained through the GBD online visualization tool. We quantified mortality changes over time for common external causes of injury for ages 15?49 years and 50?69 years separately in HICs and LMICs using negative binomial regression models. RESULTS:In 2016, there were 24,396 and 303,999 unintentional occupational injury deaths among individuals aged 15 to 69 years in HICs and LMICs, respectively, corresponding to 3.1 and 7.0 per 100,000 people. Between 1990 and 2016, unintentional occupational injury mortality for people aged 15?69 years dropped 46% (from 5.7 to 3.1 per 100,000 people) in HICs and 42% in LMICs (from 13.2 to 7.0 per 100,000 people). Sustained and large disparities existed between HICs and LMICs for both sexes and both age groups during 1990?2016 (mortality rate ratio: 2.2?2.4). All unintentional occupational injury causes of death displayed significant reduction with one exception (ages 15?49 years in HICs). Country-specific analysis revealed large variations in unintentional occupational injury mortality and changes in occupational injury mortality between 1990 and 2016. CONCLUSIONS:Despite substantial decreases in mortality between 1990 and 2016 for both HICs and LMICs, a large disparity continues to exist between HICs and LMICs. Multifaceted efforts are needed to reduce the disparity.

| S-EPMC6210857 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data