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Alimentary Pharmacology & Therapeutics Jan 2020Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision-making.
AIM
To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC.
METHODS
Bibliographic databases and conference abstracts were searched. Meta-analysis was conducted to pool sustained virologic response (SVR) estimates.
RESULTS
Fifty-six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1-90.4). Twenty-seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0-91.4) and 92.4% (95% CI 91.1-93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43-0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3-92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3-99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1-95.6).
CONCLUSION
Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 31808566
DOI: 10.1111/apt.15598 -
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 -
Acta Bio-medica : Atenei Parmensis May 2019In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild fibrosis and naïve to previous Interferon free regimen are scanty. A meta-analysis has been performed to evaluate the efficacy of velpatasvir plus sofosbuvir combination in these patients.
METHODS
All randomized or non-randomized studies, investigating the sustained virological response rate to sofosbuvir plus velpatasvir without ribavirin for 12 weeks in subjects naïve to previous DAA therapy and with fibrosis F0-F2 or F0-F3, were included in the meta-analysis.
RESULTS
A total of 16 studies enrolling 4,907 subjects met the inclusion criteria and were included in this meta-analysis. The prevalence of SVR by sofosbuvir and velpatasvir was 98% (95% CI 96-99%) in the 4,907 subjects without cirrhosis. The prevalence of SVR was similar considering the 9 clinical studies and the 7 real-world studies (98%, CI 95%: 96-99% and 98%; CI 95%: 96-99%, respectively). Considering the 4 studies enrolling 1,371 subjects without advanced liver fibrosis the prevalence of SVR was also high [96% (95% CI: 94-98%)]. Data indicate a prevalence of SVR ranging to 95-100% according to the different HCV genotypes.
CONCLUSION
Sofosbuvir plus velpatasvir therapeutic regimen was highly effective in HCV patients without advanced liver disease naïve to previous DAA regimen independently the different HCV genotypes.
Topics: Antiviral Agents; Carbamates; Controlled Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Female; Hepacivirus; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Cirrhosis; Male; Prognosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 31124995
DOI: 10.23750/abm.v90i2.8374 -
Journal of Hepatology Sep 2019The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models.
RESULTS
We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66).
CONCLUSION
Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates.
LAY SUMMARY
There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
Topics: 2-Naphthylamine; Adolescent; Adult; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Cyclopropanes; Female; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Isoquinolines; Lactams, Macrocyclic; Liver Neoplasms; Liver Transplantation; Macrocyclic Compounds; Male; Proline; Ritonavir; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Uracil; Valine; Young Adult
PubMed: 31096005
DOI: 10.1016/j.jhep.2019.04.017 -
International Journal of Infectious... Jun 2019With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after... (Meta-Analysis)
Meta-Analysis
A systematic review with meta-analysis: Is ribavirin necessary in sofosbuvir-based direct-acting antiviral therapies for patients with HCV recurrence after liver transplantation?
OBJECTIVES
With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after liver transplantation (LT). Whether ribavirin (RBV) is needed by patients after LT in combination with SOF-based DAAs remains to be determined. This meta-analysis was conducted to evaluate the necessity of RBV with SOF-based DAAs for post-LT patients.
METHODS
PubMed, Web of Science, Cochrane Library and EMBASE databases were systematically searched for eligible studies from the databases' inceptions until November 2018. We accepted the studies that included HCV recurrence in post-LT patients who were treated with SOF-based DAAs ± RBV, and evaluated the rate of sustained virological response 12 weeks (SVR12) after the end of treatment.
RESULTS
Twelve studies, comprising a total of 1466 LT recipients, were included in this study. The pooled SVR12 of these patients was 91% (95% CI: 84% to 95%). There was no statistical difference of SVR12 in the patients treated with SOF-based DAAs + RBV versus -RBV group (risk ratio [RR] = 0.97; 95% CI: 0.92 to 1.03; P = 0.35) by different therapy duration (P = 0.26), with different targets of DAAs (P = 0.13) and in different regions (P = 0.34) but a tendency for a higher incidence of anemia in the +RBV group than in the -RBV group (RR = 5.18; 95% CI: 3.41 to 7.86; p < 0.00001).
CONCLUSION
The addition of RBV may not contribute to a higher SVR rate and could increase the incidence of anemia, so RBV is not necessary in SOF-based DAAs for patients with HCV recurrence after LT.
Topics: Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C; Humans; Liver Transplantation; Male; Middle Aged; Recurrence; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 30959250
DOI: 10.1016/j.ijid.2019.03.038 -
Journal of Comparative Effectiveness... May 2019Hepatitis C virus (HCV) is a positive-stranded RNA virus which belongs to the family of , predominantly infecting liver hepatocytes. HCV infection is a major cause for...
Hepatitis C virus (HCV) is a positive-stranded RNA virus which belongs to the family of , predominantly infecting liver hepatocytes. HCV infection is a major cause for morbidity worldwide. The primary objective was to evaluate the comparative effectiveness of pan-genotypic therapies for the treatment of patients with HCV infection in Bulgaria. The databases MEDLINE, EMBASE, Cochrane Library, PubMed and clinicaltrials.gov were searched to identify studies evaluating the therapeutic efficacy of sofosbuvir/velpatasvir/voxilaprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of HCV patients. The range of sustained virologic response rates among all genotypes achieved after therapy with sofosbuvir/velpatasvir/voxilaprevir was 92-100% (8-week therapy) in treatment-naive patients and 99-100% (12-week therapy) in experienced patients. The range of sustained virologic response rates with glecaprevir/pibrentasvir was 91-100% (12-week therapy) and 97-100% (12-week therapy) with sofosbuvir/velpatasvir. Sofosbuvir/velpatasvir/voxilaprevir is a noninferior therapy offering a simple and short-term treatment regimen with high efficacy, favorable safety profile and good tolerability.
Topics: Aminoisobutyric Acids; Antiviral Agents; Bulgaria; Carbamates; Cyclopropanes; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Lactams, Macrocyclic; Leucine; Macrocyclic Compounds; Proline; Quinoxalines; Sofosbuvir; Sulfonamides; Sustained Virologic Response
PubMed: 30920311
DOI: 10.2217/cer-2018-0143 -
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 -
Value in Health : the Journal of the... Feb 2019This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework.
OBJECTIVE
This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework.
STUDY DESIGN
Taking the example of new direct-acting antivirals against hepatitis C virus, the paper asks whether and how the cost-effectiveness (CE) opinions issued by the French National Health Authority improve the information available to support the pricing decisions.
METHODS
The analysis compares the assessment of these drugs based on three different sources: CE opinions, clinical opinions, and the published cost-utility analyses (CUA) available in the literature and identified through a systematic review.
RESULTS
The results show that CE opinions bring to the fore three issues prone to impact the incremental cost utility ratio and those were not available to the decision maker through clinical opinions or published CUA: the stage of treatment initiation, the modeling of the disease progression, and the uncertainty around the efficacy rates.
CONCLUSIONS
France has introduced the criterion of the cost per QALY gained in the pricing and regulation of innovative pharmaceuticals since 2013. Our analysis shows that the use of CUA does enhance the information available to the decision makers on the value of the treatments.
Topics: Antiviral Agents; Carbamates; Cost-Benefit Analysis; Economics, Medical; France; Hepatitis C; Humans; Imidazoles; Pyrrolidines; Sofosbuvir; Therapies, Investigational; Valine
PubMed: 30711067
DOI: 10.1016/j.jval.2018.08.009 -
Ophthalmic Research 2019A meta-analysis was performed to evaluate the safety and efficacy of topical 3% diquafosol in treating patients with dry eye disease (DED). (Meta-Analysis)
Meta-Analysis
PURPOSE
A meta-analysis was performed to evaluate the safety and efficacy of topical 3% diquafosol in treating patients with dry eye disease (DED).
METHODS
Nine qualified randomized controlled trials incorporating 1,467 patients were included. Two of the reviewers selected the studies and independently assessed the risk of bias. The outcome measures were Schirmer score, tear film break-up time (TFBUT), rose bengal staining score, and corneal fluorescein staining score. To confirm the effect of diquafosol on dryness after cataract surgery, we performed a subgroup analysis according to the presence or absence of surgery.
RESULTS
We observed statistically significant improvements in scores on the Schirmer test (weighted mean difference 0.74 mm at 4 weeks; 95% CI: 0.24-1.24; I2 = 0%), fluorescein stain, rose bengal stain, and TFBUT after treatment with diquafosol compared with the group using other eye drops. As a result of the subgroup analysis of DED after cataract surgery, diquafosol was found to be more effective than the other eye drops with regard to TFBUT and rose bengal staining.
CONCLUSIONS
Topical diquafosol could be an effective treatment for DED, and also for DED after cataract surgery. Further randomized controlled trials with larger sample sizes for the different clinical types of DED are warranted to determine the efficacy and limitations of diquafosol for these different clinical types of DED.
Topics: Cataract Extraction; Dry Eye Syndromes; Humans; Ophthalmic Solutions; Polyphosphates; Randomized Controlled Trials as Topic; Tears; Uracil Nucleotides
PubMed: 30654362
DOI: 10.1159/000492896 -
Clinical Drug Investigation May 2018Hepatitis C treatment has changed considerably in recent years, and many interferon (IFN)-free therapies are now available. Considering the high rates of sustained... (Meta-Analysis)
Meta-Analysis Review
Sustained Virological Response in Special Populations with Chronic Hepatitis C Using Interferon-Free Treatments: A Systematic Review and Meta-analysis of Observational Cohort Studies.
BACKGROUND AND OBJECTIVES
Hepatitis C treatment has changed considerably in recent years, and many interferon (IFN)-free therapies are now available. Considering the high rates of sustained virological response (SVR) presented by clinical trials for these treatments, high rates of effectiveness are also expected in real-world clinical practice. Hence, this study aimed to conduct a systematic review and meta-analysis of observational cohort studies to evaluate the clinical effectiveness and safety of IFN-free therapies for hepatitis C.
METHODS
The search was performed in four electronic databases and included cohort studies that evaluated IFN-free schemes and provided data on SVR at 12 weeks after the end of treatment (SVR12) as the primary outcome. Overall and subgroup meta-analyses of patients' clinical conditions (e.g. co-infection with human immunodeficiency virus (HIV), cirrhosis, liver transplant, specific genotypes, and other conditions) were performed.
RESULTS
Sixty-eight studies encompassing a total of 24,151 patients were included for quantitative and qualitative analyses, evaluating six treatments: sofosbuvir with ledipasvir, daclatasvir, or simeprevir; daclatasvir with asunaprevir; paritaprevir/ritonavir in combination with ombitasvir and dasabuvir; and sofosbuvir with ribavirin. The overall analysis showed SVR rates of 88-96% for all treatments except sofosbuvir combined with ribavirin, which had SVR rates of approximately 80%. The results of subgroup analyses showed that the genotype 3 virus appears to be the most difficult to treat.
CONCLUSION
In order to choose the best treatment option, it is necessary to consider the patients' conditions and characteristics. In conclusion, the use of IFN-free therapies meets the high expectations created by clinical trials, including patients in special clinical conditions.
Topics: 2-Naphthylamine; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cohort Studies; Cyclopropanes; Drug Therapy, Combination; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Ribavirin; Ritonavir; Simeprevir; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Treatment Outcome; Uracil; Valine
PubMed: 29435907
DOI: 10.1007/s40261-018-0624-6