Meta-analysis

Abstract

Background The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ~20–70%. However, many of these studies are limited by different study designs and small sample sizes. Aim Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative fashion. Methods A comprehensive literature search in MEDLINE and EMBASE for ‘genotype 4’ was conducted in November 2013. Abstracts from AASLD, APASL, DDW, and EASL in 2012/2013 were reviewed. Inclusion criteria were original studies with ≥25 treatment-naïve HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were co-infection with HIV, HBV, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (p-value <0.05) and I-squared statistic (>50%). Results We included 51 studies (11,102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% (95% CI: 50–55%) (Q-statistic = 269.20, p<0.05; I2 = 81.43). On sub-group analyses, SVR was significantly associated with lower viral load, OR 3.05 (CI 1.80–5.17, p<0.001); mild fibrosis, OR 3.17 (CI 2.19–4.59, p<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI 2.87–7.69, p<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI 2.31–11.73, p<0.001). Conclusions HCV-4 patients treated with PEG IFN+RBV may expect SVR rate of ~50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis

“…Also, a previous meta-analysis on HCV-4 reported an association with SVR with favorable IL28B polymorphisms (rs12979860 CC and rs8099917 TT genotypes) [11]. The 2 studies on IL28B in our subgroup analyses showed a favorable association between SVR and rs8099917 TT genotype versus GT/GG (p = 0.014, OR: 15.0, 95% CI: 2.0-112.1) [21].…”

“…Except for a previous study about HCV-4 [11], this is the first systematic review and meta-analysis to evaluate the influence of host and viral factors in patients with chronic HCV-6 treated with PEG-IFN+RBV. In our analysis, which included 14 studies comprising a total of 819 HCV-6 patients treated with PEG-IFN+RBV, the pooled SVR rate was 79.8% (95% CI: 0.77-0.83).…”

“…PEG-IFN+RBV combination therapy continues to be a predominant option in resource-limited settings due to the high costs associated with new agents. To date, only one study reported on the influence of host and viral factors in HCV-4 [11]. Moreover, this treatment option remains elusive for patients in developing countries, such as Asia, where HCV-6 infection is high and funding for medications is inadequate.…”

Re-treatment of patients with chronic hepatitis C virus genotype 4 infection with pegylated interferon and ribavirin: a meta-analysis

“…Baseline patient characteristics, treatment protocol, and treatment responses of each study were recorded, including age, sex, prior relapser versus non-responder, treatment duration, rapid virological response (RVR), early virological response (EVR), and SVR. The extraction form initially contained a number of possible prognosticators of treatment success, as discussed by Yee et al , 3 but were removed after their omission from most articles we reviewed in-depth. Data extractions were performed by two authors (BZ and BEY).…”

“…2 Treatment success using pegylated interferon and ribavirin (P/R), defined by achieving sustained virological response (SVR), is estimated at 53% for treatment-naïve patients with HCV-4 infection. 3 This means that approximately half of the patients who undergo such regimen experience failure due to null-response or relapse. While newer direct-acting antiviral (DAA) medications have demonstrated remarkable efficacy in patients with HCV-1 infection who had experienced prior failure with P/R, 4 their cost and accessibility pose barriers to rapid worldwide adoption.…”