scholarly journals Ischemic-Free Liver Transplantation Reduces the Recurrence of Hepatocellular Carcinoma After Liver Transplantation

2021 ◽  
Vol 11 ◽  
Author(s):  
Yunhua Tang ◽  
Tielong Wang ◽  
Weiqiang Ju ◽  
Fangcong Li ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Cox Regression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Serum Lactate ◽  
Lower Serum ◽  
Cox Regression Analysis ◽  
Entire Cohort ◽  
Hcc Recurrence

Ischemia reperfusion injury (IRI) is an adverse factor for hepatocellular carcinoma (HCC) recurrence after liver transplantation. Ischemic-free liver transplantation (IFLT) is a novel transplant procedure that can largely reduce or even prevent IRI, but the clinical relevance of IFLT and the recurrence of HCC after liver transplantation are still unknown. This retrospective study compared survival outcomes, HCC recurrence, perioperative data and IRI severity following liver transplantation (LT). 30 patients received IFLT and 196 patients received conventional liver transplantation (CLT) were chosen for the entire cohort between June 2017 and August 2020. A 1:3 propensity score matching was performed, 30 IFLT recipients and 85 matched CLT patients were enrolled in propensity-matched cohorts. An univariate and multivariate Cox regression analysis was performed, and showed surgical procedure (CLT vs IFLT) was an independent prognostic factor (HR 3.728, 95% CI 1.172-11.861, P=0.026) for recurrence free survival (RFS) in HCC patients following liver transplantation. In the Kaplan–Meier analysis, the RFS rates at 1 and 3 years after LT in recipients with HCC in the IFLT group were significantly higher than those in the CLT group both in the entire cohort and propensity-matched cohort (P=0.006 and P=0.048, respectively). In addition, patients in the IFLT group had a lower serum lactate level, lower serum ALT level and serum AST level on postoperative Day 1. LT recipients with HCC in the IFLT group had a lower incidence of early allograft dysfunction than LT recipients with HCC in the CLT group. Histological analysis showed no obvious hepatocyte necrosis or apoptosis in IFLT group. In conclusion, IFLT can significantly reduce IRI damage and has the potential to be a useful strategy to reduce HCC recurrence after liver transplantation.

scholarly journals Glutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kevin Tak-Pan Ng ◽  
Oscar Wai-Ho Yeung ◽  
Yin Fan Lam ◽  
Jiang Liu ◽  
Hui Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Early Phase ◽  
Epithelial Mesenchymal Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Significant Risk ◽  
Glutathione S Transferase ◽  
Mesenchymal Transition ◽  
Hcc Recurrence

AbstractHepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H2O2-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial–mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation.

scholarly journals Factors influencing early recurrence of hepatocellular carcinoma after curative resection

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094555
Author(s):  
Yu Zhu ◽  
Lingling Gu ◽  
Ting Chen ◽  
Guoqun Zheng ◽  
Chao Ye ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Curative Resection ◽  
Cox Regression ◽  
Postoperative Recurrence ◽  
Early Recurrence ◽  
Tumor Diameter ◽  
Cox Regression Analysis ◽  
Factors Influencing ◽  
Linear Manner ◽  
Hcc Recurrence

Objective To identify the factors influencing early recurrence in patients with hepatocellular carcinoma (HCC) after curative resection. Methods Clinical data for 99 patients with HCC undergoing curative resection were analyzed. The clinicopathological factors influencing early recurrence were analyzed by Cox regression. Results Twenty-five of 99 patients (25.3%) suffered from early recurrence. There were significant differences between patients with and without recurrence in terms of tumor diameter, tumor capsular integrity, and preoperative alpha fetoprotein level. Cox regression analysis revealed that a tumor diameter >2.6 cm and preoperatively increased total bilirubin (TBL) level were risk factors for postoperative recurrence, while tumor capsular integrity had a protective effect on postoperative recurrence. After adjusting for preoperative TBL level and tumor capsular integrity, the risk of HCC recurrence was markedly increased in line with increasing tumor diameter in a non-linear manner. Conclusion Tumor diameter >2.6 cm and preoperatively increased TBL level are associated with a higher risk of early recurrence after curative resection in patients with HCC, while tumor capsular integrity is associated with a lower risk of early recurrence.

scholarly journals Indication of Liver Transplantation for Hepatocellular Carcinoma Should Be Reconsidered in Case of Microvascular Invasion and Multilocular Tumor Occurrence

2021 ◽  
Vol 10 (6) ◽  
pp. 1155
Author(s):  
Jan-Paul Gundlach ◽  
Stephan Schmidt ◽  
Alexander Bernsmeier ◽  
Rainer Günther ◽  
Victor Kataev ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Microvascular Invasion ◽  
Simultaneous Occurrence ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Disease Free

Liver transplantation (LT) is routinely performed for hepatocellular carcinoma (HCC) in cirrhosis without major vascular invasion. Although the adverse influence of microvascular invasion is recognized, its occurrence does not contraindicate LT. We retrospectively analyzed in our LT cohort the significance of microvascular invasion on survival and demonstrate bridging procedures. At our hospital, 346 patients were diagnosed with HCC, 171 patients were evaluated for LT, and 153 were listed at Eurotransplant during a period of 11 years. Among these, 112 patients received LT and were included in this study. Overall survival after 1, 3 and 5 years was 86.3%, 73.9%, and 67.9%, respectively. Microvascular invasion led to significantly reduced overall (p = 0.030) and disease-free survival (p = 0.002). Five-year disease-free survival with microvascular invasion was 10.5%. Multilocular tumor occurrence with simultaneous microvascular invasion revealed the worst prognosis. In our LT cohort, predominant bridging treatment was transarterial chemoembolization (TACE) and the number of TACE significantly correlated with poorer overall survival after LT (p = 0.028), which was confirmed in multiple Cox regression analysis for overall and disease-free survival (p = 0.015 and p = 0.011). Microvascular tumor invasion is significantly associated with reduced prognosis after LT, which is aggravated by simultaneous occurrence of multiple lesions. Therefore, indication strategies for LT should be reconsidered.

Value of HCC-MELD Score in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation

2017 ◽  
Vol 28 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Gian Piero Guerrini ◽  
Domenico Pinelli ◽  
Elena Marini ◽  
Vittorio Corno ◽  
Michela Guizzetti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Cox Regression ◽  
Prognostic Score ◽  
Disease Free Survival ◽  
Meld Score ◽  
Poor Overall Survival ◽  
Cox Regression Analysis ◽  
Improve Risk Stratification

Context: Liver transplantation (LT) is considered the ideal therapy for patients with hepatocellular carcinoma (HCC) having cirrhosis but the shortage of liver donors and the risk of dropout from the wait list due to tumor progression severely limit transplantation. A new prognostic score, the HCC-model for end-stage liver disease (HCC-MELD), was developed by combining α-fetoprotein (AFP), MELD, and tumor size, to improve risk stratification of dropout in patients with HCC. Objectives: In this study, we investigated the ability of the HCC-MELD score in predicting the posttransplant for patients fulfilling Milan criteria (MC). Design: Two hundred patients with stage II tumor were retrospectively reviewed from a total of 1290 transplants performed at our institution from October 1997 through April 2015. Cox regression analysis was performed to identify the prognostic factors impacting the posttransplant survival. Results: Overall survival at 1, 5, and 10 years was 89.3%, 71.1%, and 67.2%, whereas disease-free survival was 86.4%, 66.5%, and 52.4%, respectively. Multivariate analysis showed HCC-MELD score (hazard ratio [HR] 39.6, P < .001) and microvascular invasion (HR 2.41, P = .002) to be independent risk factors for recurrence, whereas HCC diameter (HR 1.15, P = .041), HCC-MELD (HR 15.611, P = .006), and grading (HR 2.17, P = .03) proved to be predictive factors of poor overall survival. Conclusion: Our study showed the validity of the HCC-MELD equation in the evaluation of patients undergoing LT for HCC. This score offers a reliable method to assess the risk of waiting list dropout and predict posttransplantation outcomes.

scholarly journals Methods of Attenuating Ischemia-Reperfusion Injury in Liver Transplantation for Hepatocellular Carcinoma

2021 ◽  
Vol 22 (15) ◽  
pp. 8229
Author(s):  
Łukasz Masior ◽  
Michał Grąt
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Relevant Literature ◽  
Machine Perfusion ◽  
Invasive Approach ◽  
Non Invasive ◽  
Search Terms

Hepatocellular carcinoma (HCC) is one of the most frequent indications for liver transplantation. However, the transplantation is ultimately associated with the occurrence of ischemia-reperfusion injury (IRI). It affects not only the function of the graft but also significantly worsens the oncological results. Various methods have been used so far to manage IRI. These include the non-invasive approach (pharmacotherapy) and more advanced options encompassing various types of liver conditioning and machine perfusion. Strategies aimed at shortening ischemic times and better organ allocation pathways are still under development as well. This article presents the mechanisms responsible for IRI, its impact on treatment outcomes, and strategies to mitigate it. An extensive review of the relevant literature using MEDLINE (PubMed) and Scopus databases until September 2020 was conducted. Only full-text articles written in English were included. The following search terms were used: “ischemia reperfusion injury”, “liver transplantation”, “hepatocellular carcinoma”, “preconditioning”, “machine perfusion”.

scholarly journals Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Raphael Iglesias de Oliveira Vidal ◽  
Edison Iglesias de Oliveira Vidal ◽  
Basilio de Bragança Pereira ◽  
Cachimo Combo Assane ◽  
Alexandre Ribeiro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Regression Model ◽  
Cox Regression ◽  
Microvascular Invasion ◽  
University Hospital ◽  
Explanted Liver ◽  
Hcc Recurrence

Purpose. We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). Methods. This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. Results. Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603 ), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190 ), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006 ), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001 ). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001 ). Conclusion. In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.

scholarly journals Rare Malignant Indications for Liver Transplantation: A Collaborative Transplant Study Report

2021 ◽  
Vol 8 ◽  
Author(s):  
Philipp Houben ◽  
Simon Schimmack ◽  
Christian Unterrainer ◽  
Bernd Döhler ◽  
Arianeb Mehrabi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Cox Regression ◽  
Patient Survival ◽  
Statistical Significance ◽  
Graft Loss ◽  
Limited Information ◽  
Cox Regression Analysis ◽  
Decision Making Processes ◽  
Hepatic Malignancies

Introduction: Hepatocellular carcinoma (HCC) is by far the leading malignant indication for liver transplantation (LT). Few other malignancies, including cholangiocellular carcinoma (CCC), metastases from neuroendocrine tumors (NET), and sarcomas of the liver (LSAR), also are commonly accepted indications for LT. However, there is limited information on their outcome after LT.Methods: Graft and patient survival in 14,623 LTs performed in patients with hepatocellular carcinoma, CCC, NET, and LSAR from 1988 to 2017 and reported to the Collaborative Transplant Study were analyzed.Results: The study group consisted of 13,862 patients who had HCC (94.8%), 498 (3.4%) who had CCC, 100 (0.7%) who had NET, and 163 (1.1%) who had LSAR. CCC patients showed a 5-year graft survival rate of 32.1%, strikingly lower than the 63.2% rate in HCC, 51.6% rate in NET, and 64.5% rate in LSAR patients (P &lt; 0.001 for all vs. CCC). Multivariable Cox regression analysis revealed a significantly higher risk of graft loss and death due to cancer during the first five post-transplant years in CCC vs. HCC patients (HR 1.77 and 2.56; P &lt; 0.001 for both). The same risks were increased also in NET and LSAR patients but did not reach statistical significance.Conclusion: Among patients with rare malignant indications for LT, CCC patients showed significantly impaired graft as well as patient survival compared to HCC patients. The observed differences might challenge traditional decision-making processes for LT indication and palliative treatment in specific hepatic malignancies.

scholarly journals Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae Hyun Yoon ◽  
Won Jae Lee ◽  
Sun Min Kim ◽  
Kwang Tack Kim ◽  
Sung Bum Cho ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Predictive Factors ◽  
Cox Regression ◽  
Surgical Margin ◽  
Low Risk ◽  
Extrahepatic Recurrence ◽  
Cox Regression Analysis ◽  
Hcc Recurrence ◽  
Curative Hepatectomy

AbstractExtrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

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