ABSTRACT
Liver transplantation (LT) is an important treatment of unresectable hepatocellular carcinoma (HCC). However, the prognosis of tumor recurrence remains poor.If patients with a high risk of tumor recurrence after LT can be predicted preoperatively, suitable recipients are screened so that individualized monitoring and treatment protocols may be formulated for high-risk patients.Then better outcomes are obtained.Therefore it is imperative to accurately identify the relevant risk factors and select appropriate parameters for evaluate the risks of tumor recurrence before LT.This review summarized the latest researches of preoperative clinical predictors for recurrent HCC after LT.It was intended to provide references for selecting recipients and a proper management of high-risk patients.
ABSTRACT
Objective:To investigate the value of aspartate aminotransferase/lymphocyte ratio (ALR), γ-glutamyltranspeptidase/lymphocyte ratio (GLR) and aspartate aminotransferase/alanine aminotransferase ratio (AAR) in predicting the recurrence of hepatocellular carcinoma after liver transplantation.Methods:The retrospective cohort study was conducted. The clinicopathological data of 178 patients with hepatocellular carcinoma who underwent liver transplantation in Tianjin First Central Hospital from July 2014 to June 2018 were collected. There were 156 males and 22 females, aged (54±9)years. All patients received the first time of orthotopic liver transplantation. Observation indicators: (1) follow-up; (2) the predictive value and cutoff value of each index for tumor recur-rence of patients with hepatocellular carcinoma after liver transplantation; (3) analysis of risk factors for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation; (4) cons-truction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and the Log-rank test was used for survival analysis. Factors with P<0.05 in univariate analysis were included in multivariate analysis. Univariate analysis and multivariate analysis were performed by COX proportional risk regression model with forward method. The regression coefficient was used to build the prediction model. The receiver operating characteristic curve was drawn, and the area under curve (AUC) was used to evaluate the predictive ability of prediction model. Results:(1) Follow-up. All 178 patients with hepatocellular carcinoma were followed up for 36(range, 1?74)months after liver transplantation. During the follow-up, there were 41 patients died, 61 patients with tumor recurrence and 117 cases without tumor recurrence. The 3-, 5-year overall survival rates and 3-, 5-year tumor recurrence free survival rates of patients after liver transplantation were 72.8%, 69.9% and 57.3%, 52.8%, respectively. (2) The predictive value and cutoff value of each index for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. The AUC of preoperative serum alpha fetoprotein (AFP), tumor diameter, ALR, GLR, neutrophil to lymphocyte ratio, AAR in recipients were 0.76, 0.70, 0.69, 0.65, 0.64, 0.65 (95% confidence interval as 0.68?0.83, 0.61?0.79, 0.61?0.77, 0.57?0.74, 0.56?0.73, 0.56?0.74, P<0.05), and the corresponding best cutoff value of each index were 228.00 μg/L, 5.25 cm, 92.90, 122.40, 3.00, 2.42. (3) Analysis of risk factors for tumor recurrence of patients with hepato-cellular carcinoma after liver transplantation. Results of multivariate analysis showed the preoperative serum AFP >228.88 μg/L, number of tumor as multiple, tumor diameter >5.25 cm, ALR >92.90, AAR >2.42 were indepen-dent risk factors for tumor recurrence of hepatocellular carcinoma after liver transplantation ( hazard ratio=3.13, 1.90, 2.66, 2.40, 2.75, 95% confidence interval as 1.81?5.41, 1.08?3.35, 1.49?4.74, 1.40?4.11, 1.54?4.91, P<0.05). (4) Construction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. According to the results of multivariate analysis, the preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR were used to construct the predictive model for tumor recurrence of hepatocellular carcinoma after liver transplantation. The AUC, best cutoff value, specificity and sensitivity of the predictive model were 0.83 (95% confidence interval as 0.76?0.89, P<0.05), 5.5, 80.3% and 73.8%. Of the 178 patients, there were 110 patients with low risk of tumor recurrence (scoring as 0?5) and 68 patients with high risk of tumor recurrence (scoring as 6?16) after liver transplantation. The 1-, 3-, 5-year tumor recurrence free survival rates and 1-, 3-, 5-year overall survival rates of patients with high risk of tumor recurrence were 27.7%, 18.2%, 18.2% and 63.7%, 48.9%, 48.9%, respectively. The above indicators of patients with low risk of tumor recurrence were 92.3%, 82.4%, 74.6% and 90.4%, 87.7%, 83.6%, respectively. There were significant differences of the above indicators between patients with high risk of tumor recurrence and low risk of tumor recurrence ( χ2=67.83, 21.95, P<0.05). Conclusions:The preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR are independent influencing factors for tumor recurrence of hepato-cellular carcinoma after liver transplantation. The predictive model constructed based on the above indexes has a good prediction efficiency.
ABSTRACT
Objective To develop a new model for predicting recurrence after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria based on related preoperative and postoperative indicators. Methods A retrospective analysis was performed for the clinical data of the patients with HCC beyond Milan criteria who underwent orthotopic liver transplantation for the first time in Tianjin First Central Hospital from August 2014 to July 2018, and according to the presence or absence of recurrence during follow-up, the patients were divided into recurrence group and no-recurrence group. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the risk factors for recurrence-free survival after surgery. A new model was developed for recurrence after liver transplantation in the patients with HCC beyond Milan criteria based on the risk factors identified. The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive performance, and the Hosmer-Lemeshow test was used to assess the goodness of fit of the model. Results A total of 117 patients with HCC beyond Milan criteria were enrolled in this study, with a median follow-up time of 24 (1-74) months. A total of 53 patients (45.3%) experienced recurrence after surgery, among whom 52 (98.1%) had recurrence within 3 years after surgery, with a median time to recurrence of 6 (1-52) months. The Cox proportional hazards regression analysis showed that preoperative serum alpha-fetoprotein (AFP) >769 ng/mL, neutrophil-lymphocyte ratio (NLR) >3.75, and ki67 index >0.25 were independent risk factors for recurrence-free survival after liver transplantation. The model established based on these three risk factors had an AUC of 0.843, with good sensitivity (88.7%) and specificity (70.3%). The optimal cut-off value was selected according to the maximization of Youden index, and then the patients were divided into low-risk group (0-1 point) and high-risk group (1.5-4 points). The log-rank test showed that the low-risk group had significantly higher 3-and 5-year recurrence-free survival rates than the high-risk group (84.1%/72.0% vs 10.9%/10.9%, χ 2 =29.425, P < 0.001). Conclusion Liver transplantation for HCC beyond Milan criteria should be performed with caution, and the predictive model established based on preoperative AFP, NLR, and ki67 index can accurately assess the indication for liver transplantation in such patients.