Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Comparison of Tacrolimus and Cyclosporine Combined With Methotrexate for Graft Versus Host Disease Prophylaxis After Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: After patients receive hematopoietic stem cell transplantation (HSCT), both cyclosporine (CsA) and tacrolimus (TAC) in combination with methotrexate (MTX) are recommended as the standard prophylaxis strategy for graft versus host disease (GVHD) by the European Group of Blood and Marrow Transplantation. However, the advantage of TAC combined with MTX lacks conclusive evidence. METHODS: We searched online databases for studies comparing CsA + MTX and TAC + MTX in patients who received HSCT. The odds ratio (OR) and 95% confidence interval (CI) were applied to compare the pooled data. RESULTS: We found a significant reduction in the grade II to IV acute GVHD (aGVHD) rate (OR, 0.42; CI, 0.28-0.61; P < 0.00001), grade III to IV aGVHD rate (OR, 0.59; CI, 0.38-0.92; P = 0.02), chronic GVHD rate (OR, 0.79; CI, 0.62-1.00; P = 0.05), and nonrelapse mortality rate (OR, 0.62; CI, 0.40-0.95; P = 0.03) and an increase in the overall survival (OS) rate (only in those received from unrelated donor) (OR, 1.30; CI, 1.15-1.48; P < 0.0001) in the TAC + MTX group. Similar outcomes occurred for the relapse rate and disease-free survival rate in both groups. CONCLUSIONS: TAC + MTX has a superior effect in the prevention of aGVHD in patients who received HSCT and further prolongs the OS in patients who received from unrelated donor transplants. CsA + MTX prolongs the OS in patients who received HSCT from HLA-identical sibling donors. The leukemic relapse and disease-free survival rate were not different between the 2 regimens. Thus, we conclude that TAC + MTX was superior to CsA + MTX, especially for HSCT patients with nonmalignant disorders. Further studies are still required to evaluate the effect of TAC or CsA combined with other suppressors in the treatment regimen following HSCT.

Accuracy of computed tomography for detecting hepatic steatosis in donors for liver transplantation: A meta-analysis.

BACKGROUND: The accuracy of computed tomography (CT) for detecting donor hepatic steatosis (HS) before liver transplantation is not well established. METHODS: A meta-analysis was performed to determine the accuracy of CT for HS detection in liver donor candidates. Pooled sensitivity, specificity, positive and negative likelihood ratios, hierarchical summary receiver operating characteristic (HSROC) curves, and the area under the curve (AUC) were estimated using HSROC and bivariate random-effects models. RESULTS: Twelve studies involving 1782 subjects were eligible for this meta-analysis. For detecting significant HS (>10%-30% steatosis in liver pathology) with CT in liver donors, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 0.81 (95% confidence interval [CI]: 0.70-0.89), 0.94 (95% CI: 0.90-0.96), 13.7 (95% CI: 8.1-23.1), and 0.20 (95% CI: 0.12-0.33). The AUC was 0.95 (95% CI: 0.92-0.96). For detecting the presence of HS, these corresponding diagnostic estimates were 0.50 (95% CI: 0.36-0.64), 0.90 (95% CI: 0.83-0.95), 5.2 (95% CI: 3.1-8.9), 0.55 (95% CI: 0.42-0.72), and 0.80 (95% CI: 0.76-0.83). Moderate-to-high heterogeneity was detected. CONCLUSION: Computed tomography shows high accuracy in detecting significant HS while poor accuracy in detecting the presence of HS in liver donors. Donors estimated to have significant HS by CT may avoid unnecessary liver biopsy.

Accuracy of MR Imaging and MR Spectroscopy for Detection and Quantification of Hepatic Steatosis in Living Liver Donors: A Meta-Analysis.

Purpose To determine the accuracy of magnetic resonance (MR) imaging for detection and quantification of hepatic steatosis (HS) in living liver donor candidates. Materials and Methods A systematic search of the literature was performed to find studies on the diagnostic and quantitative accuracy of MR imaging for assessment of HS in liver donors. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used, and patient selection, index text, reference standard, and study flow and timing were assessed to evaluate the quality of each included study. Pooled sensitivity, specificity, positive and negative likelihood ratios, hierarchical summary receiver operating characteristic (ROC) curves, and the area under the curve were estimated by using hierarchical summary ROC and bivariate random-effects models. Results Eight studies involving 934 subjects were eligible for the meta-analysis. For detection of HS with MR imaging and/or MR spectroscopy in living liver donors, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio, respectively, were 0.89 (95% confidence interval [CI]: 0.75, 0.95), 0.84 (95% CI: 0.76, 0.89), 5.53 (95% CI: 3.71, 8.25), and 0.14 (95% CI: 0.06, 0.31). The area under the curve was 0.92 (95% CI: 0.89, 0.94). For detection of substantial HS (>10% to >30% HS at liver pathologic examination, as defined in each study), these corresponding diagnostic estimates were 0.91 (95% CI: 0.82, 0.95), 0.89 (95% CI: 0.84, 0.93), 8.30 (95% CI: 5.47, 12.59), 0.10 (95% CI: 0.05, 0.21), and 0.96 (95% CI: 0.93, 0.97), respectively. Moderate heterogeneity was detected. No publication bias was detected (P = .12). Conclusion MR imaging and MR spectroscopy show high sensitivity and specificity for detection of HS, especially when HS is substantial, and may be useful for noninvasive evaluation of HS in living liver donors. © RSNA, 2016 Online supplemental material is available for this article.

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.

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.

Liver transplantation versus liver resection in the treatment of hepatocellular carcinoma: a meta-analysis of observational studies.

BACKGROUND: A number of cohort studies have compared the outcomes of liver transplantation (LT) and liver resection (LR) in hepatocellular carcinoma (HCC) patients. However, the effects of LT versus LR remain unclear. We searched electronic databases and reference lists for relevant articles published before February 2013. METHODS: The primary endpoints were pooled using random-effects models to model potential heterogeneity, including overall survival (OS), disease-free survival, and recurrence rate. RESULTS: We found similar 1-year OS (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.81-1.43; P=0.61) yet significantly better 3-year OS (OR, 1.47; 95% CI, 1.18-1.84; P<0.001) and 5-year OS (OR, 1.77; 95% CI, 1.45-2.16; P<0.001) after LT compared with LR with relative risk differences of 9% (P<0.001) and 14% (P<0.001), respectively. The 1-, 3-, and 5-year difference-free survival were 13%, 29%, and 39% higher (P<0.001 in all) in LT recipients than LR patients. Additionally, recurrence rate was 30% less (P<0.001) in LT than LR. Furthermore, better 5-year difference-free survival (P<0.001) and recurrence rates (P<0.05) were yielded after LT when patients from the entire HCC population were included. CONCLUSIONS: When including all the 62 previous studies comparing LT and resection, LT provides increased survival and lower recurrence rates than LR for HCC patients. These results of disease-free survival and recurrence rate are similar among early HCC patients with Child-Turcotte-Pugh class A cirrhosis. However, summary ORs and risk differences cannot be interpreted as causal effects of LT versus LR.