Adjuvant chemotherapy for patients with primary hepatocellular carcinoma: a meta-analysis.

Numerous studies have investigated the effects of adjuvant chemotherapy for primary hepatocellular carcinoma (HCC) patients. We conducted this analysis to evaluate the efficacy of adjuvant chemotherapy in HCC patients after hepatectomy. PubMed/MEDLINE, EMBASE, Cochrane, and other databases were searched for eligible studies. The major endpoints were overall survival (OS) and disease-free survival (DFS). The pooled odds ratio (OR) was calculated using a random-effects model to summarize the results. In the meta-analysis of 13 randomized control trials (RCTs) and 35 observational studies with 4747 patients, hepatectomy plus adjuvant chemotherapy showed superiority over hepatectomy alone in 1-year DFS (OR = 1.86, 1.38-2.51, p < 0.001), 3-year DFS (OR = 2.37, 1.73-3.24, p < 0.001) and 5-year DFS (OR = 1.99, 1.55-2.55, p < 0.001), as well as 1-year OS (OR = 2.16, 95% confidence interval 1.75-2.68, p < 0.001), 3-year OS (OR = 1.77, 1.48-2.13, p < 0.001) and 5-year OS (OR = 1.92, 1.44-2.56, p < 0.001). Subgroup and sensitivity analysis revealed that only adjuvant TACE had significant survival benefits. The meta-analysis of studies involving patients with portal vein tumor thrombus (PVTT), but not other factors related to recurrence risk, revealed favorable outcomes of the Treatment arm over the Control arm. The present study shows that adjuvant chemotherapy can improve outcomes for HCC patients. The benefits of adjuvant TACE have been confirmed whereas the effects of other adjuvant chemotherapy modalities remain uncertain. Adjuvant chemotherapy is likely to be more applicable to certain patient populations for instance those with PVTT, but further research in identifying these patient factors is of importance for tailoring adjuvant therapies to individual patients in the future.

Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: a meta-analysis.

Sirolimus (SRL) is a novel immunosuppressant with antitumor properties. We performed a meta-analysis to determine whether SRL can improve patient survival and decrease the risks of tumor recurrence in patients with a pretransplant diagnosis of hepatocellular carcinoma (HCC). We searched databases for controlled clinical trials assessing the survival and oncological benefits of SRL for liver transplant recipients with pretransplant HCC. Five studies with a total of 2950 participants were included in this study. In comparison with SRL-free regimens, SRL-based regimens improved overall survival at 1 [odds ratio (OR) = 4.53, 95% confidence interval (95% CI) = 2.31-8.89], 3 (OR = 1.97, 95% CI = 1.29-3.00), and 5 years (OR = 2.47, 95% CI = 1.72-3.55). The pooled results showed that in comparison with SRL-free regimens, SRL-based regimens decreased tumor recurrence (OR = 0.42, 95% CI = 0.21-0.83). No significant differences in the frequencies of episodes of major posttransplant complications were observed between the groups. In conclusion, SRL is generally safe and prolongs patient survival in liver transplant recipients with pretransplant HCC.

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: a meta-analysis.

Because of the severe organ shortage, living donor liver transplantation (LDLT) offers a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatocellular carcinoma (HCC). However, the higher recurrence rate of HCC after LDLT and the indication criteria remain controversial. By conducting a quantitative meta-analysis, we sought to compare the survival outcomes and recurrence rates with LDLT and DDLT for patients with HCC. Comparative studies of LDLT and DDLT for HCC, which were identified by a comprehensive literature search, were included in this study. The evaluated outcomes included patient survival, recurrence-free survival (RFS), and recurrence rates at defined time points. Seven studies with a total of 1310 participants were included in this study. For LDLT and DDLT recipients, we found comparable patient survival rates [1 year, odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.62-1.73; 3 years, OR = 1.07, 95% CI = 0.77-1.48; and 5 years, OR = 0.64, 95% CI = 0.33-1.24] and RFS rates (1 year, OR = 0.86, 95% CI = 0.54-1.38; 3 years, OR = 1.04, 95% CI = 0.69-1.58; and 5 years, OR = 1.11, 95% CI = 0.70-1.77). Moreover, we found no significant differences in the 1-, 3-, or 5-year recurrence rates between LDLT and DDLT recipients (1 year, OR = 1.55, 95% CI = 0.36-6.58; 3 years, OR = 2.57, 95% CI = 0.53-12.41; and 5 years, OR = 1.21, 95% CI = 0.44-3.32). A subgroup analysis revealed similar outcomes for patients with HCC meeting the Milan criteria. These findings demonstrate that for HCC patients (especially those within the Milan criteria), LDLT represents an acceptable option that does not compromise patient survival or increase HCC recurrence in comparison with DDLT.

Outcomes of Technical Variant Liver Transplantation versus Whole Liver Transplantation for Pediatric Patients: A Meta-Analysis.

OBJECTIVE: To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation. METHODS: To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model. RESULTS: The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61). CONCLUSIONS: Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation.

Performance of polymerase chain reaction techniques detecting granzyme B in the diagnosis of acute renal rejection: a meta-analysis.

BACKGROUND: Studies have shown that granzyme B expression was up-regulated during acute renal rejection, which provides hopes for a noninvasive and reliable diagnostic method. However, the diagnostic performance has not been assessed systematically so far. METHODS: Relevant materials were searched from electronic databases before February 1, 2012. Clinical studies that reported the diagnostic performance of detecting granzyme B mRNA using polymerase chain reaction techniques in acute renal rejection patients were included. The data of true-positive, true-negative, false-positive, and false-negative cases identified by granzyme B detection were extracted from each data set of the relevant materials. The publication year, sample origin, mRNA quantification method, and housekeeping gene were extracted as potential confounding variables. RESULTS: Fourteen studies with a total of 514 cases were included. The overall diagnostic performance of granzyme B was pooled sensitivity of 0.76 (95% confidence interval [CI], 0.69-0.81), pooled specificity of 0.87 (95% CI, 0.83-0.90), diagnostic odds ratio of 19.27 (95% CI, 1.20-195.00), and area under the summary receiver operating characteristic curve value of 0.8900±0.0270. The univariate analysis of potential variables showed no statistically significant variations. CONCLUSIONS: Despite interstudy variability, granzyme B mRNA demonstrated both sensitivity and specificity in the diagnosis of acute rejection and showed consistency under circumstances of methodologic changes. However, the clinical practice requires careful consideration and other supplementary tests.

Can immune cell function assay identify patients at risk of infection or rejection? A meta-analysis.

BACKGROUND: The Cylex ImmuKnow cell function assay (CICFA) is being considered as a possible tool for identification of infection and rejection in transplant recipients. However, the predictive capability of CICFA is still unclear. METHODS: Herein, we performed a meta-analysis to assess the efficacy of CICFA in identifying risks of infection and rejection posttransplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of CICFA were pooled. Summary receiver operating characteristic curves were used to represent the overall test performance. RESULTS: Nine studies met the inclusion criteria. The pooled estimates for CICFA in identification of infection risk were poor, with a sensitivity of 0.58 (95% confidence interval [CI]: 0.52-0.64), a specificity of 0.69 (95% CI: 0.66-0.70), a positive likelihood ratio of 2.37 (95% CI: 1.90-2.94), a negative likelihood ratio of 0.39 (95% CI: 0.16-0.70), and a diagnostic odds ratio of 7.41 (95% CI: 3.36-16.34). The pooled estimates for CICFA in identifying risk of rejection were also fairly poor with a sensitivity of 0.43 (95% CI: 0.34-0.52), a specificity of 0.75 (95% CI: 0.72-0.78), a positive likelihood ratio of 1.30 (95% CI: 0.74-2.28), a negative likelihood ratio of 0.96 (95% CI: 0.85-1.07), and a diagnostic odds ratio of 1.19 (95% CI: 0.65-2.20). CONCLUSION: The current evidence suggests that CICFA is not able to identify individuals at risk of infection or rejection. Additional studies are still needed to clarify the usefulness of this test for identifying risks of infection and rejection in transplant recipients.

Efficacy and tolerability of telaprevir for chronic hepatitis virus C genotype 1 infection: a meta-analysis.

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; I(2) =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; I(2) =85%, and OR=4.05 [1.56, 10.56], P=0.004; I(2) =92%, respectively), while it was comparable in the 12-week treatment group (OR=1.32 [0.63, 2.75], P=0.46; I(2) =35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR=0.28 [0.16, 0.49], P<0.001; I(2) =76%). However, the incidence of SAE (OR=1.56 [1.15, 2.10], P=0.004; I(2) =0%) and study discontinuation due to adverse events (OR=2.24 [1.43, 3.50], P<0.001; I(2) =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.

Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

BACKGROUND: The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. METHODS: PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. RESULTS: Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. CONCLUSIONS: The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

Performance of polymerase chain reaction techniques detecting perforin in the diagnosis of acute renal rejection: a meta-analysis.

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.

Calcineurin-inhibitor minimization in liver transplant patients with calcineurin-inhibitor-related renal dysfunction: a meta-analysis.

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; I(2) = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I(2) = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I(2) = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I(2) = 0%; survival: Z = 0.28, P = 0.78; I(2) = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I(2) = 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.