Role of the criteria based on preoperative serological indexes of AFP and GGT in predicting long-term survival of patients with hepatocellular carcinoma after liver transplantation / 器官移植

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

Liver transplantation in China: Achievements over the past 30 years and prospects for the future.

Over the last three decades, liver transplantation (LT) in China has made breakthroughs from scratch. Now, new techniques are being continuously incorporated. However, LT in China differs from that in other countries due to cultural differences and the disease burden. The advances made in and the current issues with LT in China need to be summarized. Living donor LT (LDLT) has developed dramatically in China over the last 30 years, with the goal of increasing transplant opportunities and dealing with the shortage of donors. Western candidate selection criteria clearly are not appropriate for Chinese patients. Thus, the current authors reviewed the literature, and this review has focused on the topics of technological advancements in LDLT and Chinese candidate selection. The Milan criteria in wide use emphasize tumor morphology rather than pathology or biomarkers. α-fetoprotein (AFP) and pathology were incorporated as predictors for the first time in the Hangzhou criteria. Moreover, Xu et al. divided the Hangzhou criteria into type A (tumor size ≤ 8 cm or tumor size > 8 cm but AFP ≤ 100 ng/mL) and type B (tumor size > 8 cm but AFP between 100 and 400 ng/mL), with type B serving as a relative contraindication in the event of a liver donor shortage. In addition, surgeons in Chengdu and Shanghai have the ability to perform a laparoscopic hepatectomy for right and left lobe donors, respectively. China has established a complete LT system, including recipient criteria suitable for Chinese people, a fair donor allocation center, a transplant quality monitoring platform, and mature deceased donor or living donor LT techniques.

Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation.

BACKGROUND: Long-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) patients remains poor because of tumor recurrence. To improve the prognosis of HCC patients after LT, we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center. METHODS: In total, data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis. The patients were divided into the following three groups: Group 1, within the Milan and Hangzhou criteria (n = 51); Group 2, beyond the Milan but within the Hangzhou criteria (n = 36); and Group 3, beyond the Milan and Hangzhou criteria (n = 112). Survival probabilities for the three groups were calculated using multivariate Cox regression analysis. The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis. RESULTS: Child-Pugh stage C and hepatitis B virus (HBV) infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria. The overall survival rates of the 199 patients showed statistically significant differences among the three groups (P < 0.001). Moreover, no significant difference was noted in the survival rate between Group 1 and Group 2 (P > 0.05). Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria (OR = 0.478; 95% CI: 0.308-0.741; P = 0.001). CONCLUSIONS: Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT. The Hangzhou criteria were effective and analogous compared with the Milan criteria. Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.

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.

Expansion of the Milan criteria without any sacrifice: combination of the Hangzhou criteria with the pre-transplant platelet-to-lymphocyte ratio.

BACKGROUND: The Hangzhou criteria expand the Milan criteria safely and effectively in selecting hepatocellular carcinoma (HCC) candidates for liver transplantation (LT), but some patients exceeding the Milan but fulfilling the Hangzhou criteria still show poor outcomes due to early tumor recurrence. In this study, the platelet-to-lymphocyte ratio (PLR) was employed to differentiate high-risk tumor recurrence recipients, and a new method combining PLR and the Hangzhou criteria was established. METHODS: The clinical data of 343 LT for HCC were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was used to determine the PLR cut-off value to stratify patients exceeding the Milan but fulfilling the Hangzhou criteria. The recurrence-free survival (RFS) of recipients was compared after stratification. The Hangzhou criteria & PLR method was proposed and its feasibility was validated by ROC analysis. RESULTS: PLR 120 was the most significant cut-off value when comparing RFS of patients exceeding the Milan but fulfilling the Hangzhou criteria. After stratification, the 1-, 3-, and 5-year RFS of patients exceeding the Milan but fulfilling the Hangzhou criteria with PLR < 120 were 84.2%, 73.3%, and 73.3%, respectively, comparable with 85.7%, 73.9%, and 72.8%, respectively, in patients fulfilling the Milan criteria (P = 0.885). Patients exceeding the Milan but fulfilling the Hangzhou criteria with PLR ≥ 120 showed poor outcomes, which were similar in patients exceeding the Hangzhou criteria; 1-, 3-, and 5-year RFS were only 37.5%, 12.5%, and 12.5% vs. 32.3%, 17.6%, and 15.1%, respectively (P = 0.887). ROC analysis demonstrated that the ROC area of the Hangzhou criteria & PLR method was 0.768 for RFS. Multivariate analysis confirmed that PLR ≥ 120 was independently associated with RFS of patients exceeding the Milan but fulfilling the Hangzhou criteria. CONCLUSIONS: The Hangzhou criteria combined with the pre-transplant PLR can accurately exclude high-risk tumor recurrence recipients; this approach expands the Milan criteria effectively without any sacrifice.

Comparison of survival and tumor recurrence rates in patients undergoing liver transplantation for hepatitis B-related hepatocellular carcinoma using Milan, Shanghai Fudan and Hangzhou criteria.

OBJECTIVES: To assess the performance of the Milan, Shanghai Fudan and Hangzhou criteria based on a preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: Using a prospectively collected database, the data of consecutive patients with hepatitis B-related HCC undergoing LT at the Department of Liver Surgery of Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilling the Milan, Shanghai Fudan and Hangzhou criteria were compared using log-rank test. RESULTS: Altogether 148 patients were enrolled in the study, among whom 88 fulfilled the Milan criteria and 24 and 39 were beyond Milan but within the Shanghai Fudan or Hangzhou criteria, respectively. After a median follow-up of 44 months, survival rates did not differ among the three groups (P = 0.8780). Recurrence rates were significantly higher for newly eligible patients by the Shanghai Fudan or Hangzhou criteria compared with those within the Milan criteria. CONCLUSIONS: The Milan criteria should be used as the preferred criteria for the selection of hepatitis B-related HCC for LT. Considering the high tumor recurrence rates and donor scarcity, a moderate expansion of the Milan criteria must be performed cautiously until high-quality clinical trials are conducted.

Clinical value of Hangzhou Criteria in selection of patients with hepatocellular carcinoma for living donor liver transplantation / 中华器官移植杂志

Objective To investigate the clinical value of Hangzhou Criteria in selection of patients with hepatocellular carcinoma(HCC)for living donor liver transplantation(LDLT)and their effects on recipient's post-transplant survival.Methods A retrospective analysis was conducted on 43 patients with HCC who underwent LDLT in our center.All of the recipients were classified into subgroups according to Milan Criteria,Up-to-Seven Criteria and Hangzhou Criteria,and post-transplant total survival rate and tumor-free survival rate were compared among the criteria.Results The number of patients within Hangzhou Criteria was 61.5 %(8/13)more than that within Milan Criteria and 23.5 %(4/17)more than that within Up-to-Seven Criteria.The 1-,and 3-years total survival rate and tumor-free survival rate of the recipients within Milan Criteria(n=13)were 100 %,80.0 % and 84.6 %,84.6 %,those of the recipients within Up-to-Seven Criteria(n=17)were 100 %,75.2 % and 87.5 %,81.2 %,and those of the recipients within Hangzhou Criteria(n=21)were 100 %,80.0 % and 89.5 %,84.2 %,respectively.There was no significant difference among the three criteria in total survival rate and tumor-free survival rate(P>0.05).Conclusion Hangzhou Criteria further enrolled more liver transplantation candidates without decline of total survival rate and tumor-free survival.It is a more effective selection of HCC recipients for LDLT.