The efficacy and safety of telaprevir-based regimens for treating chronic hepatitis C virus genotype 1 infection: a meta-analysis of randomized trials.

OBJECTIVE: Previous studies have reported that telaprevir is effective for treating chronic hepatitis C virus (HCV) genotype 1 infection; however, the efficacy and safety of telaprevir-based regimens remain uncertain. METHODS: To assess the efficacy and safety of telaprevir in patients with chronic HCV genotype 1 infection, we conducted a meta-analysis of all available randomized controlled trials (RCT) comparing the efficacy and safety of the addition of telaprevir to a standard regimen (combination of telaprevir with peginterferon and ribavirin, TPR group) with the standard regimen alone (peginterferon and ribavirin, PR group). RESULTS: Ultimately, six RCTs involving a total of 2,759 patients with chronic HCV genotype 1 infection were included in this meta-analysis. The outcomes showed that the sustained virologic response (SVR) rate was significantly higher in the TPR group (1,284/1,932, 66.5%) than in the PR group (296/827, 35.8%) with a pooled odds ratio (OR) [3.81, 95% confidence interval (CI) 2.43-5.96, p<0.001]. The results also showed that the relapse rate was significantly lower in the TPR group (190/1,484, 12.8%) than in the PR group (140/425, 32.9%) with a pooled risk ratio (RR) (0.40; 95% CI 0.24-0.66, p<0.001). However, there was an increased risk of serious adverse events in the TPR group (RR=1.45, 95% CI 1.12-1.87, p=0.005). CONCLUSION: Telaprevir-based regimens can significantly increase the SVR rate and reduce the relapse rate in patients with chronic HCV genotype 1 infection. However, the safety of telaprevir-based regimens still requires further study.

Radiosensitivity enhancement by arsenic trioxide in conjunction with hyperthermia in the EC-1 esophageal carcinoma cell line.

OBJECTIVE: To explore the effect on radiosensitivity of arsenic trioxide (As203) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. METHOD: Inhibition of EC-1 cell proliferation at different concentrations of As203 was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC50 value and choice of 20% of the IC50 as the experimental drug concentration. Blank control, As203, hyperthermia, radiotherapy group, As203 + hyperthermia, As203 + radiotherapy, hyperthermia + radiotherapy and As203 + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. RESULTS: As203 exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an IC50 of 18.7 µmol/L. After joint therapy of As203 + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the G2/M phase, and as the ratio of cells in G0/G1 and S phases decreased, cell death became more pronounced. CONCLUSION: As203 and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, As203 and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells.

AIM: To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming growth factor-beta (1) (TGF-beta (1)) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV-GN). METHODS: The levels of serum TGF-beta(1) were measured by specific enzyme linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell (HK-2) was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative (20 cases) and HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer. RESULTS: The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01%+/-5.85% and 17.58%+/-8.35%, HBV DNA negative serum group 8.12%+/-2.80% and 6.96%+/-2.76% than those in control group 4.25%+/-0.65% and 2.33%+/-1.09%, respectively (P<0.01). The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum (P<0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA (r = 0.657). The level of serum TGF-beta (1) in CHB group was 163.05+/-91.35 microg/L, significantly higher as compared with 81.40+/-40.75 microg/L in the control group (P<0.01). CONCLUSION: The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-beta (1) may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.