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Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatic cirrhosis and hepatocellular carcinoma, and HCV genotype 1 is the most prevalent genotype and is resistant to current standard therapy. We performed this meta-analysis to evaluate the efficacy and safety of telaprevir-based therapy for chronic HCV genotype 1 infection. Methods: We included randomized controlled trials with no year or language restriction. All data were analyzed using a random-effects model by Review Manager v5.0. The primary outcome was the proportion of patients achieving sustained virologic response (SVR), and the secondary outcomes were HCV relapse rate, incidence of severe adverse events (SAEs), and discontinuation due to adverse events. Results: The proportion of achieving SVR was significantly higher in the telaprevir group (odds ratio [OR] = 3.40 [1.92, 6.00], P<0.0001; I² = 87%) regardless of a patients' previous treatment status. It was also significantly higher in the 24-week and 48-week treatment groups (OR = 4.52 [2.08, 9.81], P<0.001; I² = 85%, and OR = 4.05 [1.56, 10.56], P = 0.004; I² = 92%, respectively), while it was comparable in the 12-week treatment group (OR = 1.32 [0.63, 2.75], P = 0.46; I² = 35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR = 0.28 [0.16, 0.49], P<0.001; I² = 76%). However, the incidence of SAE (OR = 1.56 [1.15, 2.10], P = 0.004; I² = 0%) and study discontinuation due to adverse events (OR = 2.24 [1.43, 3.50], P<0.001; I² = 37%) were significantly higher in the telaprevir group. Conclusion: Despite its higher incidence of SAEs and discontinuation due to adverse events, telaprevir-based therapy can increase the proportion of achieving SVR in both previously treated and untreated chronic HCV-1 infected patients. [ABSTRACT FROM AUTHOR]

Objective: To summarize the experience with salvage liver transplantation (SLT) for patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic resection in a single center. Methods: A total of 376 adult patients with HCC underwent orthotopic liver transplantation (OLT) at Organ Transplantation Center, the First Affiliated Hospital of Sun Yat-sen University, between 2004 and 2008. Among these patients, 36 underwent SLT after primary liver curative resection due to intrahepatic recurrence. During the same period, one hundred and fortyseven patients with HCC within Milan criteria underwent primary OLT (PLTW group), the intra-operative and post-operative parameters were compared between these two groups. Furthermore, we compared tumor recurrence and patient survival of patients with SLT to 156 patients with HCC beyond Milan criteria (PLTB group). Cox Hazard regression was made to identify the risk factors for tumor recurrence. Results: The median interval between initial liver resection and SLT was 35 months (1-63 months). The intraoperative blood loss (P<0.05) and transfusion volume (P<0.05) were larger in the SLT group than in the PLTW group. The operation time was longer in the SLT group (P<0.05). The post-operative complications incidence, tumor recurrence rate, patients' survival rate, and tumor-free survival rate were comparable between these two groups (all P>0.05). When compared to those patients with HCC beyond Milan criteria undergoing primary OLT, patients undergoing SLT achieved a better survival and a lower tumor recurrence. Cox Proportional Hazards model showed that vascular invasion, including macrovascular and microvascular invasion, as well as AFP level >400 IU/L were risk factors for tumor recurrence after LT. Conclusions: In comparison with primary OLT, although SLT is associated with increased operation difficulties, it provides a good option for patients with HCC recurrence after curative resection. [ABSTRACT FROM AUTHOR]

Background: Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance. Methodology/Principal Findings: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88); pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90); diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97); and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance. Conclusions/Significance: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal rejection. These results suggest a great diagnostic potential for perforin mRNA detection as a reliable marker of acute rejection in renal allograft recipients. [ABSTRACT FROM AUTHOR]

Background: Inadequate liver regeneration (LR) is still an unsolved problem in major liver resection and small-for-size syndrome post-living donor liver transplantation. A number of microRNAs have been shown to play important roles in cell proliferation. Herein, we investigated the role of miR-26a as a pivotal regulator of hepatocyte proliferation in LR. Methodology/Principal Findings: Adult male C57BL/6J mice, undergoing 70% partial hepatectomy (PH), were treated with Ad5-anti-miR-26a-LUC or Ad5-miR-26a-LUC or Ad5-LUC vector via portal vein. The animals were subjected to in vivo bioluminescence imaging. Serum and liver samples were collected to test liver function, calculate liver-to-body weight ratio (LBWR), document hepatocyte proliferation (Ki-67 staining), and investigate potential targeted gene expression of miR-26a by quantitative real-time PCR and Western blot. The miR-26a level declined during LR after 70% PH. Down-regulation of miR-26a by anti-miR-26a expression led to enhanced proliferation of hepatocytes, and both LBWR and hepatocyte proliferation (Ki-67+ cells %) showed an increased tendency, while liver damage, indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (T-Bil), was reduced. Furthermore, CCND2 and CCNE2, as possible targeted genes of miR-26a, were up-regulated. In addition, miR-26a over-expression showed converse results. Conclusions/Significance: MiR-26a plays crucial role in regulating the proliferative phase of LR, probably by repressing expressions of cell cycle proteins CCND2 and CCNE2. The current study reveals a novel miRNA-mediated regulation pattern during the proliferative phase of LR. [ABSTRACT FROM AUTHOR]

Background: Introduction of calcineurin-inhibitor (CNI) has made transplantation a miracle in the past century. However, the side effects of long-term use of CNI turn out to be one of the major challenges in the current century. Among these, renal dysfunction attracts more and more attention. Herein, we undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction. Methods: We included randomized trials with no year and language restriction. All data were analyzed using random effect model by Review Manager 5.0. The primary endpoints were glomerular filtration rate (GFR), serum creatinine level (sCr) and creatinine clearance rate (CrCl), and the secondary endpoints were acute rejection episodes, incidence of infection and patient survival at the end of follow-up. Results: GFR was significantly improved in CNI minimization group than in routine CNI regimen group (Z = 5.45, P<0.00001; I2 = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I2 = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I2 = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I2 = 0%; survival: Z = 0.28, P = 0.78; I2 = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I2 = 0%). Conclusion: CNI minimization can preserve or even improve renal function in liver transplant patients with renal impairment, while sharing similar short term acute rejection rate and patient survival with routine CNI regimen. [ABSTRACT FROM AUTHOR]

Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that downregulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity. [ABSTRACT FROM AUTHOR]