Outcomes of liver transplantation for hepatocellular carcinoma in donation after circulatory death compared with donation after brain death: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Due to organ shortages, liver transplantation (LT) using donation-after-circulatory-death (DCD) grafts has become more common. There is limited and conflicting evidence on LT outcomes using DCD grafts compared to those using donation-after-brain death (DBD) grafts for patients with hepatocellular carcinoma (HCC). We aimed to summarize the current evidence on the outcomes of DCD-LT and DBD-LT in patients with HCC. MATERIALS AND METHODS: Online databases were searched for studies comparing DCD-LT and DBD-LT outcomes in patients with HCC and a meta-analysis was conducted using fixed- or random-effects models. RESULTS: Five studies involving 487 (33.4%) HCC DCD-LT patients and 973 (66.6%) DBD-LT patients were included. The meta-analysis showed comparable 1-year [relative risk (RR)=0.99, 95%CI:0.95 to 1.03, p=0.53] and 3-year [RR=0.99, 95%CI:0.89 to 1.09, p=0.79] recurrence-free survival. The corresponding 1-year [RR=0.98, 95%CI:0.93 to 1.03, p=0.35] and 3-year [RR=0.94, 95%CI:0.87 to 1.01, p=0.08] patient survival and 1-year [RR=0.91, 95%CI:0.71 to 1.16, p=0.43] and 3-year [RR=0.92, 95%CI:0.67 to 1.26, p=0.59] graft survival were also comparable. There were no significant differences between the two cohorts regarding the tumor characteristics, donor/recipient risk factors and the incidence of post-operative complications, including acute rejection, primary non-function, biliary complications and retransplantation. CONCLUSIONS: Based on the current evidence, it has been found that comparable outcomes can be achieved in HCC patients using DCD-LT compared to DBD-LT, particularly when employing good quality graft, strict donor and recipient selection, and effective surgical management. The decision to utilize DCD-LT for HCC patients should be personalized, taking into consideration the risk of post-LT HCC recurrence. (PROSPERO ID: CRD42023445812).

Survival outcomes after caudate lobectomy for hepatocellular carcinoma: systematic review and meta-analysis.

BACKGROUND: Caudate lobectomy (CLB) remains the most effective treatment for caudate lobe hepatocellular carcinoma (CL-HCC). However, there is controversy regarding the survival after CLB. This meta-analysis aims to investigate the survival outcomes following CLB for the treatment of CL-HCC. METHODS: In line with PRISMA and MOOSE guidelines, a search for all eligible studies was performed. The pooled estimates of survival rates and hazard ratios (HRs) with their 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. RESULTS: Sixteen studies comprising 864 patients met the inclusion criteria. The pooled estimates of 3- and 5-year overall survival (OS) rates were 62.3% and 42.9% respectively and the pooled estimate of 3- and 5-year recurrence-free survival (RFS) rates were 39.3% and 24.4% respectively. CL-HCC showed inferior OS (HR:1.39, 95% CI: 0.91-1.88, P < 0.001) and RFS (HR:1.33, 95% CI: 1.10-1.56, P < 0.001) than other sites HCC. Isolated CLB showed better OS (HR:0.9, 95% CI:0.39-1.41, p < 0.001) and RFS (HR:0.76, 95% CI: 0.03-1.5, P = 0.04) than combined CLB. CONCLUSIONS: The survival outcomes for CL-HCC after CLB are lower compared to other sites HCC. Isolated CLB offers better survival outcomes compared to combined CLB. However, choosing isolated or combined approaches should be prioritized according to patient and tumour characteristics.

Comparative Analysis of Donor Liver Allograft Outcomes in Hepatocellular Carcinoma Patients Who Underwent Liver Transplant.

OBJECTIVES: Liver transplant for patients with hepatocellular carcinoma involves 3 main types of donor allografts: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Data on this topic are limited, and controversies exist regarding liver transplant outcomes in hepatocellular carcinoma patients who have received these allografts. MATERIALS AND METHODS: Data from 490 hepatocellular carcinoma patients who received liver transplant from 2015 to 2021 at the Shulan (Hangzhou) Hospital were retrospectively analyzed. Participants were divided into 3 cohorts according to allograft type: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Kaplan-Meier and Cox regression methods were used to evaluate patient survival, graft survival, and recurrence-free survival rates after liver transplant. RESULTS: Kaplan-Meier analysis revealed that 3-year patient survival rates were 69.2% for donations after brain death, 69.2% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .42); the 3-year graft survival rates were 53.3% for donations after brain death, 56.4% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .44); and 3-year recurrence-free survival rates were 55% for donations after brain death, 56.6% for donations after cardiac death, and 39.5% for donations after brain and cardiac death (P = .46). Complications were also similar across the 3 cohorts (P = .36). Multivariable analysis showed that intraoperative red blood cell transfusion (hazard ratio: 1.820; P = .042) and early allograft dysfunction (hazard ratio: 3.240; P = .041) were independent risk factors for graft survival. CONCLUSIONS: Similar outcomes can be achieved for hepatocellular carcinoma patients who undergo liver transplant with donations after brain death, donations after cardiac death, or donations after brain and cardiac death allografts, especially when strict donor selection criteria are applied.

Predictors of post-recurrence survival in hepatocellular carcinoma patients following liver transplantation: Systematic review and meta-analysis.

BACKGROUND: Data on predictors of post-recurrence survival (PRS) of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) have not been reviewed and analysed systematically. We aimed to systematically analyse all published data on the predictors for PRS. METHODS: In accordance with PRISMA and MOOSE guidelines, online search of PubMed and EMBASE databases was done for all reports that evaluate the predictors of PRS based on multivariate analyses. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% CIs were conducted to assess the potential predictors of PRS. RESULTS: Twenty-three studies met the inclusion criteria. Among the 11,868 patients involved, 1921 (16%) had HCC recurrence within a median time of 16 months. The following were recurrence and tumour-related predictors: time to recurrence (<1 year; HR: 1.97; p < 0.001), AFP level at recurrence(≥100 ng/ml; HR: 1.82; p < 0.001), multiple recurrence (HR: 1.22; p < 0.001), bone recurrence (HR: 2.10; p < 0.001), poor differentiation (HR: 1.52; p < 0.001), intrahepatic recurrence (HR: 0.91; p = 0.03), extrahepatic recurrence (HR: 1.87; p < 0.001), Milan criteria at LT (HR: 1.34; p < 0.001), microvascular invasion (HR: 1.59; p < 0.001), multiorgan recurrence (HR: 1.28; p < 0.001), and recurrent HCV infection (HR: 1.21; p < 0.001). The treatment-related predictors were as follows: surgical resection (HR: 0.33; p < 0.001), mTOR inhibitors (HR: 0.63; p < 0.001), sorafenib (HR: 1.00; p = 0.01), palliative treatment (HR: 3.07; p < 0.001), RFA (HR: 0.47; p < 0.001), and radiotherapy (HR: 1.19; p < 0.001). CONCLUSIONS: Systematic evaluation of these predictors could guide surgeons to design risk-adapted algorithms for the management of post-LT HCC recurrence to construct reliable predictive models and to design future prospective studies or clinical trials.

Prediction model based on blood urea nitrogen and the leukocyte count for intestinal necrosis in patients with portal vein system thrombosis: a retrospective study.

BACKGROUND: Portal vein system thrombosis (PVST) is a serious and potentially fatal disease. No definite parameter can predict intestinal necrosis in patients with PVST to justify early surgical intervention. The current study aimed to explore a simple and accurate model to predict the occurrence of intestinal necrosis in patients with PVST. METHODS: Records of patients admitted to our emergency department with PVST from January 2010 to October 2018 were reviewed. Clinical parameters, including patient history, physical examination, and the results of laboratory investigations, were analyzed. RESULTS: Sixty-nine patients (27 females) were included. All patients were admitted to our emergency department because of abdominal pain. Fourteen patients required exploratory laparotomy, and intestinal necrosis was confirmed. Seven patients received thrombolytic therapy, and the other 48 patients had completed anticoagulation successfully. According to multivariate logistic regression, high blood urea nitrogen (BUN) (OR: 1.413, P=0.048) and the leukocyte count (OR: 1.180, P=0.005) were associated with intestinal necrosis, and a prediction model for intestinal necrosis (PMIN) based on the BUN and leukocyte count was established. CONCLUSIONS: The PMIN score could effectively predict intestinal necrosis in patients with PVST.

Systematic review: risk prediction models for recurrence of hepatocellular carcinoma after liver transplantation.

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a significant clinical problem associated with poor surgical outcomes. This study aims to summarize the current evidence on risk prediction models of HCC recurrence after LT. PubMed and EMBASE were searched to May 25, 2019, for relevant articles. Studies originally designed to develop or validate a risk prediction model for HCC recurrence after LT were included. Two independent authors summarized the study characteristics and evaluated the risk of bias and applicability concerns in the included studies. From 26 included studies, 18 original risk prediction models were determined, but only five models were externally validated. The average number of predictors involved in the construction of risk models was three. The most frequently employed predictors were alpha-fetoprotein, tumor size, vascular invasion, tumor number, tumor differentiation, and neutrophil-lymphocyte ratio. Most studies showed good discriminatory performance (AUC >0.75). The overall quality of the included studies was generally low. Most of the original models lacked the highly recommended external and prospective validation in diverse populations. The AFP model was the well-validated preoperative risk model that can stratify patients into high- and low-risk groups.

Glutamine synthetase promotes tumor invasion in hepatocellular carcinoma through mediating epithelial-mesenchymal transition.

AIM: Glutamine synthetase (GS) levels increase gradually with the development of hepatocellular carcinogenesis. In this study, we aimed to investigate the clinical significance of GS and the underlying mechanism of GS promoting hepatocellular carcinoma (HCC) invasion. METHODS: Serum concentration of GS and α-fetoprotein (AFP) in HCC patients, liver cirrhosis patients, and healthy individuals were detected. The GS-mRNA level and its prognostic value were explored in an independent HCC cohort from The Cancer Genome Atlas database. GS expression in HCC tissue and matched para-tumor tissue was determined. The effect of GS on HCC invasion was assessed in vitro and in vivo. RESULTS: The serum GS and AFP level in HCC patients was higher than that in healthy controls and liver cirrhosis patients. The area under the receiver operating characteristic curve for HCC diagnosis was 0.848 and 0.861 for GS and AFP, respectively. The area under the receiver operating characteristic curve of GS for diagnosis of AFP-negative HCC was 0.913. Combining GS with AFP achieved a diagnostic sensitivity and specificity of 82.5% and 93%, respectively. The GS level was higher in tumor tissues than that in para-tumor tissues. High GS expression was associated with poor prognosis of moderately differentiated HCC patients. In vitro, GS exerted an influence on HCC cell migration by mediating epithelial-mesenchymal transition. The lung and liver metastatic model of HCC further confirmed that GS expression affected the invasion of HCC cells in vivo. CONCLUSIONS: GS is a useful biomarker for HCC diagnosis, especially for AFP-negative patients. In addition, GS affects HCC metastasis through mediating epithelial-mesenchymal transition.

Preoperative risk stratification for early recurrence of HBV-related hepatocellular carcinoma after deceased donor liver transplantation: a five-eight model development and validation.

BACKGROUND: Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence. METHODS: Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n = 486) and validation(n = 262) cohorts. A multivariate analysis was performed and the five-eight model was developed. RESULTS: A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84% had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5-8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0-5 points), medium-(6-8 points) and high-risk (> 8 points) with 2-year post-LT recurrence rate of (5,20 and 51%,p <  0.001) respectively. The 5-8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort. CONCLUSIONS: The 5-8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT.

Prediction of Early Recurrence of Hepatocellular Carcinoma in Patients with Cirrhosis Who Had Received Deceased Donor Liver Transplantation: A Multicenter Study.

BACKGROUND Early recurrence after liver transplantation (LT) is still a clinical problem. This multicenter study evaluated the Milan, Hangzhou, and AFP model-based criteria for prediction of early recurrence of HCC in patients with cirrhosis who had undergone LT. MATERIAL AND METHODS From the China Liver Transplant Registry (CLTR) database, we analyzed data of 589 HCC patients who had undergone LT between Jan 2015 and Jan 2019. Imaging data and AFP levels were evaluated immediately before LT. Recurrence and overall survival rates at 2 years were tested using the Kaplan-Meier estimate. The Milan criteria, Hangzhou criteria, and AFP model-based criteria were evaluated. RESULTS We found that 62.0%, 91.2%, and 67.6% of patients were within the Milan criteria, Hangzhou criteria, and AFP model-based criteria, respectively. The 2-year recurrence rate was 8.9%, 15.8%, and 11.8% with corresponding overall survival of 85.3%, 82.7%, and 86.5%, respectively. The 2-year recurrence rate was different in patients fulfilling and exceeding the AFP model-based criteria among patients who met either the Milan criteria (7.9% vs. 18.8%, HR=3.83, p=0.006) or Hangzhou criteria (12.0% vs. 27.6%, HR=2.95, p<0.001). However, the 2-year recurrence rate was not significantly different among patients who were beyond either the Milan or Hangzhou criteria. CONCLUSIONS For the prediction of early recurrence of HCC in patients with cirrhosis after liver transplantation, Milan criteria, Hangzhou criteria, and AFP model-based criteria are effective predictive tools for stratification of patients into low- and high-risk groups of recurrence with different prognoses. The AFP model-based criteria can identify a subgroup of patients with high risk of recurrence among patients who met either Milan or Hangzhou criteria.

Middle hepatic vein reconstruction in adult right lobe living donor liver transplantation improves recipient survival.

BACKGROUND: The efficacy and necessity of middle hepatic vein (MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation (LDLT) remain controversial. The present study aimed to evaluate the survival beneficiary of MHV reconstructions in LDLT. METHODS: We compared the clinical outcomes of liver recipients with MHV reconstruction (n = 101) and without MHV reconstruction (n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. RESULTS: The overall survival (OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation (P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments (segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment (segment 5 or segment 8) hepatic vein reconstruction (P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction (P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS (hazard ratio=0.519, 95% CI: 0.282-0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction (28.7% vs 11.6%, P = 0.027). CONCLUSIONS: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries (segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.