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Annals of Hepatology 2017
Meta-Analysis Review
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Benzimidazoles; Chi-Square Distribution; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepacivirus; Hepatitis C; Humans; Male; Middle Aged; Odds Ratio; Ribavirin; Sofosbuvir; Sustained Virologic Response; Time Factors; Treatment Outcome; Young Adult
PubMed: 28233739
DOI: 10.5604/16652681.1231562 -
Daru : Journal of Faculty of Pharmacy,... Apr 2017Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding Sofosbuvir (SOF), an HCV polymerase inhibitor to the conventional therapy of Pegylated-interferon (PegIFN) plus Ribavirin (RBV) can increase the rate of sustained virologic response (SVR) among HCV-infected patients. This study was conducted to determine the effect of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using systematic review with meta-analysis.
METHODS
In this study, electronic databases including PubMed, Scopus, Science Direct, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the efficacy of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection were included in the meta-analysis.
RESULTS
After screening of 757 records, we included five articles with total sample size of 411 to the meta-analysis. Based on the fixed-effect model (χ = 5.29, P = 0.26 and I = 24.4%), pooled SVR rate for treatment regimen of PegIFN and RBV plus SOF was calculated as 88.54% (95% CI = 85.77%-91.32%).
CONCLUSIONS
Combination therapy with PegIFN and RBV plus SOF results in high treatment response in patients with HCV genotype 1 infection.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Ribavirin; Sofosbuvir
PubMed: 28427463
DOI: 10.1186/s40199-017-0177-x -
The Pan African Medical Journal 2019approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In...
INTRODUCTION
approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment.
METHODS
data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles' government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer's perspective and combined into incremental cost effectiveness ratios (ICERs).
RESULTS
the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds.
CONCLUSION
treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection.
Topics: Antiviral Agents; Benzimidazoles; Cost-Benefit Analysis; Female; Fluorenes; Hepatitis C, Chronic; Humans; Male; Markov Chains; Quality-Adjusted Life Years; Sex Factors; Seychelles; Sofosbuvir; Substance Abuse, Intravenous; Uridine Monophosphate
PubMed: 31384341
DOI: 10.11604/pamj.2019.33.26.17742 -
Virology Journal Mar 2019Whether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the safety and effectiveness of SOF-based regimen in the setting of stage 4 and 5 chronic kidney disease (CKD).
METHODS
We conducted a systematic literature search in PubMed, Web of Science, EMBASE and Google Scholar with searching strategy: (sofosbuvir OR Sovaldi OR Harvoni OR Epclusa OR Vosevi) AND (severe kidney impairment OR severe renal impairment OR end-stage renal disease OR dialysis OR renal failure OR ESRD OR renal insufficiency OR hepatorenal syndrome OR HRS). Sustained virological response (SVR12/24) rate and serious adverse event (SAE) rate with 95% confidence intervals were aggregated. Subgroup analysis was implemented to evaluate the impact of treatment strategy and patient characteristics.
RESULTS
Twenty-one studies met inclusion criteria, totaling 717 HCV infected patients with CKD stage 4 or 5 (58.4% on dialysis). Pooled SVR12/24 was 97.1% (95% CI 93.9-99.3%), and SAE rate was 4.8% (95% CI 2.1-10.3%). There was no significant difference at SVR12/24 (97.1% vs 96.2%, p = 0.72) or SAE rate (8.8% vs 2.9%, p = 0.13) between subgroups applying full or decreased dose of sofosbuvir. Cirrhotic and non-cirrhotic patients achieved comparable sustained virological response (RR 0.93, 95% CI 0.85-1.02). Four studies reported eGFR/serum creatinine pre- and post- treatment, with no significant modification.
CONCLUSIONS
Our study suggests SOF-based regimen might be used safely and effectively in patients living with HCV infection/stage 4-5 CKD, with normal and reduced dose of sofosbuvir. Prospective and well-controlled trials are needed to confirm these findings.
TRIAL REGISTRATION
PROSPERO CRD42018107440 .
Topics: Antiviral Agents; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Insufficiency, Chronic; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 30871566
DOI: 10.1186/s12985-019-1140-x -
Journal of Clinical Pharmacy and... Aug 2022Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to SOF-based medication regimens in several clinical scenarios, despite its well-known toxicities. The aim of our study is to systematically review and analyse the impact of adding RBV to SOF-based medication regimens on clinical outcomes among HCV patients.
METHODS
Included studies were randomized trials comparing the same SOF-based medication regimens with and without RBV in HCV patients and measuring serious adverse events (SAEs) and/or sustained virologic response at 12 weeks post-treatment (SVR-12). Two investigators independently searched PubMed and Cochrane Library through September 2021. The Cochrane Risk of Bias tool was used to assess trials quality. Clinical outcomes were analysed as risk ratios (RR) using a random effects model using R version 4.1.2.
RESULTS AND DISCUSSION
Our study included a total of 26 trials with 5058 HCV patients. Quality assessment showed moderate risk of bias for most trials. Upon adding RBV, there was no significant difference in SAEs (RR 1.07, 95% CI: 0.77-1.48, I = 10%), nor an impact on SVR-12 (RR 1.00, 95% CI: 0.98-1.01, I = 41%). There was no evidence of publication bias for either outcome. Subgroup analysis consistently showed lack of benefit among HCV subgroups. Additionally, NCT01826981 was identified as the main source of heterogeneity in the SVR-12 outcome.
WHAT IS NEW AND CONCLUSION
Our findings suggest nonsignificant differences in safety and efficacy between SOF-based medication regimens with and without RBV which should be considered in clinical practice.
Topics: Antiviral Agents; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Ribavirin; Sofosbuvir; Treatment Outcome
PubMed: 35678040
DOI: 10.1111/jcpt.13698 -
Annals of Medicine Dec 2023The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies.
AIM
To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection.
METHODS
We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109).
RESULTS
Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration.
CONCLUSION
Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.
Topics: Humans; Sofosbuvir; Hepacivirus; Sustained Virologic Response; Antiviral Agents; Hepatitis C; Drug Therapy, Combination; Hyperglycemia; Genotype; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36655629
DOI: 10.1080/07853890.2023.2168745 -
PloS One 2022Contribution of UCP1 single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for... (Meta-Analysis)
Meta-Analysis
Contribution of UCP1 single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for these conditions varies across populations. We tested whether UCP1 SNPs A-3826G, A-1766G, Ala64Thr and A-112C are associated with common CMP and their risk factors across Armenia, Greece, Poland, Russia and United Kingdom. This case-control study included genotyping of these SNPs, from 2,283 Caucasians. Results were extended via systematic review and meta-analysis. In Armenia, GA genotype and A allele of Ala64Thr displayed ~2-fold higher risk for CMP compared to GG genotype and G allele, respectively (p<0.05). In Greece, A allele of Ala64Thr decreased risk of CMP by 39%. Healthy individuals with A-3826G GG genotype and carriers of mutant allele of A-112C and Ala64Thr had higher body mass index compared to those carrying other alleles. In healthy Polish, higher waist-to-hip ratio (WHR) was observed in heterozygotes A-3826G compared to AA homozygotes. Heterozygosity of A-112C and Ala64Thr SNPs was related to lower WHR in CMP individuals compared to wild type homozygotes (p<0.05). Meta-analysis showed no statistically significant odds-ratios across our SNPs (p>0.05). Concluding, the studied SNPs could be associated with the most common CMP and their risk factors in some populations.
Topics: Cardiovascular Diseases; Case-Control Studies; Cytidine Monophosphate; Genetic Predisposition to Disease; Humans; Metabolic Diseases; Polymorphism, Single Nucleotide; Prevalence; Uncoupling Protein 1
PubMed: 35482655
DOI: 10.1371/journal.pone.0266386 -
BMC Infectious Diseases Nov 2017Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions... (Review)
Review
BACKGROUND
Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development.
METHODS
According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016).
RESULTS
Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses.
CONCLUSIONS
On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.
Topics: Antiviral Agents; Carbamates; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Pyrrolidines; Ribavirin; Sofosbuvir; Treatment Outcome; Valine
PubMed: 29145802
DOI: 10.1186/s12879-017-2820-z -
Scientific Reports Aug 2020Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir... (Meta-Analysis)
Meta-Analysis
Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91-98%). The efficacy of the SOF-based regimen was 92% (95% CI 80-99%), 98% (95% CI 96-100%), and 100% (95% CI 95-100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5-29%), followed by anemia 15% (95% CI 3-31%), and nausea or vomiting 14% (95% CI 4-27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33-59%) compared to ribavirin-free regimens (3%, 95% CI 0-9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe.
Topics: Antiviral Agents; Hepatitis C; Humans; Kidney Failure, Chronic; Sofosbuvir
PubMed: 32868869
DOI: 10.1038/s41598-020-71205-5 -
The Cochrane Database of Systematic... Aug 2020Stroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been proposed for the recovery from, and treatment of, ischemic stroke. One of them is citicoline. This review assessed the benefits and harms of citicoline for treating patients with acute ischemic stroke.
OBJECTIVES
To assess the clinical benefits and harms of citicoline compared with placebo or any other control for treating people with acute ischemic stroke.
SEARCH METHODS
We searched in the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS until 29 January 2020. We searched the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. Additionally, we also reviewed reference lists of the retrieved publications and review articles, and searched the websites of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in any setting including participants with acute ischemic stroke. Trials were eligible for inclusion if they compared citicoline versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
We selected RCTs, assessed the risk of bias in seven domains, and extracted data by duplicate. Our primary outcomes of interest were all-cause mortality and the degree of disability or dependence in daily activities at 90 days. We estimated risk ratios (RRs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed-effect and random-effects model meta-analyses. We assessed the overall quality of evidence for six pre-specified outcomes using the GRADE approach.
MAIN RESULTS
We identified 10 RCTs including 4281 participants. In all these trials, citicoline was given either orally, intravenously, or a combination of both compared with placebo or standard care therapy. Citicoline doses ranged between 500 mg and 2000 mg per day. We assessed all the included trials as having high risk of bias. Drug companies sponsored six trials. A pooled analysis of eight trials indicates there may be little or no difference in all-cause mortality comparing citicoline with placebo (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07; I² = 0%; low-quality evidence due to risk of bias). Four trials found no difference in the proportion of patients with disability or dependence in daily activities according to the Rankin scale comparing citicoline with placebo (21.72% versus 19.23%; RR 1.11, 95% CI 0.97 to 1.26; I² = 1%; low-quality evidence due to risk of bias). Meta-analysis of three trials indicates there may be little or no difference in serious cardiovascular adverse events comparing citicoline with placebo (8.83% versus 7.77%; RR 1.04, 95% CI 0.84 to 1.29; I² = 0%; low-quality evidence due to risk of bias). Overall, either serious or non-serious adverse events - central nervous system, gastrointestinal, musculoskeletal, etc. - were poorly reported and harms may have been underestimated. Four trials assessing functional recovery with the Barthel Index at a cut-off point of 95 points or more did not find differences comparing citicoline with placebo (32.78% versus 30.70%; RR 1.03, 95% CI 0.94 to 1.13; I² = 24%; low-quality evidence due to risk of bias). There were no differences in neurological function (National Institutes of Health Stroke Scale at a cut-off point of ≤ 1 points) comparing citicoline with placebo according to five trials (24.31% versus 22.44%; RR 1.08, 95% CI 0.96 to 1.21; I² = 27%, low-quality evidence due to risk of bias). A pre-planned Trial Sequential Analysis suggested that no more trials may be needed for the primary outcomes but no trial provided information on quality of life.
AUTHORS' CONCLUSIONS
This review assessed the clinical benefits and harms of citicoline compared with placebo or any other standard treatment for people with acute ischemic stroke. The findings of the review suggest there may be little to no difference between citicoline and its controls regarding all-cause mortality, disability or dependence in daily activities, severe adverse events, functional recovery and the assessment of the neurological function, based on low-certainty evidence. None of the included trials assessed quality of life and the safety profile of citicoline remains unknown. The available evidence is of low quality due to either limitations in the design or execution of the trials.
Topics: Activities of Daily Living; Acute Disease; Aged; Aged, 80 and over; Bias; Brain Ischemia; Cause of Death; Cytidine Diphosphate Choline; Humans; Middle Aged; Nootropic Agents; Randomized Controlled Trials as Topic; Recovery of Function; Stroke
PubMed: 32860632
DOI: 10.1002/14651858.CD013066.pub2