1.
Efficacy of vitamin D supplementation in combination with conventional antiviral therapy in patients with chronic hepatitis C infection: a meta-analysis of randomised controlled trials.
Kim, HB, Myung, SK, Lee, YJ, Park, BJ, ,
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2018;(2):168-177
Abstract
BACKGROUND Although a contributory role of vitamin D levels for the development of chronic hepatitis C has been suggested, the efficacy of vitamin D supplementation in combination with conventional antiviral therapy consisting of pegylated interferon-α (Peg-IFN-α) injection and oral ribavirin (RBV) remains unclear. We investigated its efficacy in the treatment of chronic hepatitis C via a meta-analysis of randomised controlled trials. METHODS We searched PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and the bibliographies of relevant articles to locate additional publications in September 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. RESULTS Of 522 articles meeting our initial criteria, a total of seven open-label, randomised controlled trials involving 548 participants, were included in the final analysis. Vitamin D supplementation in combination with Peg-IFN-α injection and oral RBV significantly increased the rate of viral response for hepatitis C at 24 weeks after treatment in a random-effects meta-analysis (relative risk = 1.30; 95% confidence interval = 1.04-1.62; I2 = 75.9%). Also, its significant efficacy was observed in patients with hepatitis C virus genotype 1, which is known to be refractory to antiviral therapy. CONCLUSIONS In summary, we observed that additional use of vitamin D has a positive effect on sustained viral response rates of patients with chronic hepatitis C infection. However, we cannot establish the efficacy because of substantial heterogeneity, a small sample size and a low methodological quality.
2.
Real-world effectiveness of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in patients with hepatitis C virus genotype 1 or 4 infection: A meta-analysis.
Wedemeyer, H, Craxí, A, Zuckerman, E, Dieterich, D, Flisiak, R, Roberts, SK, Pangerl, A, Zhang, Z, Martinez, M, Bao, Y, et al
Journal of viral hepatitis. 2017;(11):936-943
Abstract
UNLABELLED The direct-acting antiviral regimen of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r)±dasabuvir (DSV)±ribavirin (RBV) demonstrated high rates of sustained viral response at post-treatment week 12 (SVR12) in clinical trials for treatment of hepatitis C virus (HCV) genotypes (GT) 1 and 4. To confirm the effectiveness of this regimen in the real world, we conducted meta-analyses of published literature on 30 April 2016. Freeman-Tukey transformation determined the SVR rate within GTs 1a, 1b and 4, as well as specific SVR rates by cirrhosis or prior treatment experience status. Rates of virologic relapse, hepatic decompensation, drug discontinuation and serious adverse events were also analysed. In total, 20 cohorts across 12 countries were identified, totalling 5158 patients. The overall SVR12 rates were 96.8% (95% CI 95.8-97.7) for GT1 and 98.9% (95% CI 94.2-100) for GT4. For GT1a patients, the SVR rates were 94% and 97% for those with or without cirrhosis, and 94% overall. For GT1b patients, the SVR rates were 98% and 99% for those with or without cirrhosis, and 98% overall. The virologic relapse rate of GT1 patients was 1.3%, across 3524 patients in nine studies that reported this parameter. The rate of hepatic decompensation was less than 1% across five studies, including 3440 patients, 70% of which had cirrhosis. CONCLUSIONS Real-world SVR12 rates for OBV/PTV/r±DSV±RBV were consistently high across HCV GT1 and four irrespective of cirrhosis status or prior HCV treatment experience, confirming effectiveness within a diverse patient population across multiple cohorts and countries.
3.
Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naïve Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis.
Suwanthawornkul, T, Anothaisintawee, T, Sobhonslidsuk, A, Thakkinstian, A, Teerawattananon, Y
PloS one. 2015;(12):e0145953
Abstract
BACKGROUND The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR). However, there has been no evidence from randomized controlled trials (RCTs) that directly compare the efficacy among the different regimens of DAAs. AIM: Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1. METHODS Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD). Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue). Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using 'pmeta' command in STATA program. RESULTS Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR) of 1.98 (95% CI 1.24, 3.14), 1.46 (95% CI: 1.22, 1.75), and 1.68 (95% CI: 1.14, 2.46), respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with/without ribavirin, SOF plus SMV with/without ribavirin, SOF plus DCV with/without ribavirin, and PrOD with/without ribavirin, (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone. In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of having SVR12 was not significantly different between these two regimens, with the pooled RR of 0.99 (95% CI: 0.97, 1.01). Regarding adverse drug events, risk of serious adverse drug events, anemia and fatigue were relatively higher in treatment regimens with PR than the treatment regimens without PR. The main limitation of our study is that a subgroup analysis according to dosages and duration of treatment could not be performed. Therefore, the dose and duration of recommended treatment have been suggested in range and not in definite value. CONCLUSIONS Both DAA plus PR and dual DAA regimens should be included in the first line drug for treatment naïve HCV genotype 1 because of the significant clinical benefits over PR alone. However, due to high drug costs, an economic evaluation should be conducted in order to assess the value of the investment when making coverage decisions.