Excessive intraoperative blood loss independently predicts recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Several studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear. METHODS: A total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan-Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis. RESULTS: The median follow-up was 28 months (range, 1-131 months). Kaplan-Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60-3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64-3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L. CONCLUSIONS: Excessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.

Validation of a criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation.

The aim of this study was to validate a criteria-specific long-term survival prediction model (MHCAT) in a large cohort of hepatocellular carcinoma (HCC) patients after liver transplantation (LT) in China. Independent risk factors in MHCAT were retrospectively analysed for HCC patients recorded in the China Liver Transplant Registry. Survival predictions for each patient were calculated using MHCAT scores and the Metroticket formula separately, and the prediction efficacy of MHCAT and Metroticket was compared using the area under ROC curve (c-statistic). A total of 1371 LTs for HCC were analysed in the study, with a median follow-up of 22.2 months (IQR 6.1-72.4 months). The proportions meeting the Milan, UCSF, Fudan and Hangzhou criteria were 34.4%, 39.7%, 44.2% and 51.9%, respectively. The c-statistics for MHCAT predictions of 3- and 5-year survival rates of HCC recipients were 0.712-0.727 and 0.726-0.741, respectively. Among these patients, 1298 LTs for HCC were ultimately selected for the comparison analysis for prediction efficacy. The c-statistic of MHCAT for predictions of 3-year survival with reference to the Milan, UCSF and Fudan criteria was significantly increased compared with that for Metroticket (p < 0.05). In conclusion, MHCAT can effectively predict long-term survival for HCC recipients after LT.

Suppression of allograft rejection by Tim-1-Fc through cross-linking with a novel Tim-1 binding partner on T cells.

Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4(+) effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4(+) T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4(+) T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3(+) cells in splenic CD4(+) T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4(+)CD25(-) T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection.

Prediction of survival after liver transplantation for chronic severe hepatitis B based on preoperative prognostic scores: a single center's experience in China.

BACKGROUND: The aim of this study was to estimate the utility of a preoperative model of end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score in predicting the prognosis after othotopic liver transplantation (OLT) for chronic severe hepatitis B (CSHB) and explore the prognostic factors. METHODS: The outcome of 137 patients who underwent OLT using donors after cardiac death (DCDs) for CSHB in our center was reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method; the log-rank test was used for univariate analysis; and the Cox proportional hazards regression model was used for prognostic factors screening. RESULTS: The overall mortality rate was 33.6% (46/137); and 1-month, 6-month, 1-year, and 5-year patient survival rates were 75.8, 72.0, 71.0, and 60.1%, respectively. Most patients (33/46) died during the first month after OLT. The area under the curve values generated by the receiver operating characteristics curves were 0.82 [95% confidence interval (CI) 0.72-0.92] and 0.68 (95% CI 0.58-0.79), respectively (P < 0.01), for the MELD and CTP models in predicting 1-month mortality after OLT. Patients with a preoperative MELD score <33.8 or a CTP score <12.5 had significantly better prognosis than those with higher scores (P < 0.05). Other mortality predictors include hepatic encephalopathy, preoperative infection, serum creatinine > or = 1.5 mg/dl. CONCLUSIONS: The MELD score was more efficient than the CTP score for evaluating the short-term prognosis in patients with CSHB undergoing OLT using DCDs, which should be taken into consideration during graft allocation.

Report of 8 cases of liver retransplantation.

BACKGROUND: Retransplantation of the liver is required for several complications of primary grafting, such as primary allograft non-function, hepatic artery thrombosis, biliary problems, or chronic ductopenic rejection. Surgeons usually take regrafting as the only pathway to treat those patients who are considered to have a poor outcome after the first operation. Whether the retransplantation is early or late, further attempts at rescue with a second or more grafts are associated with higher mortality and morbidity. However, retransplantation plays a role in improving survival of the patients. Therefore, it is necessary to summarize the experiences in liver retransplantation, as well as the factors influencing operative effects. METHOD: The clinical data of 8 patients who received liver retransplantation in our center were analyzed retrospectively. RESULTS: Complications of the biliary tract occurred in 5 of the 8 patients, chronic rejection in 2, and embolism in the hepatic artery in 1. Infections occurred in 7 patients before engraftment. Patient 1 had developed renal failure before the surgery, and he died of severe infection and multi-organ failure after transplantation. Patient 4 had a massive hemorrhage during the operation and also died of multi-organ failure after transplantation. Patient 7 developed intracranial hemorrhage and abdominal infection and died soon after transplantation. The other 5 patients recovered and discharged from the hospital. CONCLUSIONS: Liver retransplantation is the only measure that can be taken to save the lives of patients whose liver allograft fails to function. It is very important that the indications and time of retransplantation are carefully selected. Factors leading to harmful effects on retransplantation include the preoperative condition of the recipient, a difficult and prolonged operation, massive hemorrhage during the operation, and severe complications after the surgery.