Introduction: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Lenvatinib and sorafenib are the first line choice in untreated advanced hepatocellular carcinoma. However, their efficacy in patients with LT is still unknown. We analyzed our 5-year experience with LT for HBV related HCC to identify predictors of recurrence and potential beneficiaries from targeted therapy of Lenvatinib or sorafenib.
Materials and Methods: A novel clinicopathologic risk score predicting post-transplant HCC recurrence was developed from a multivariate competing-risk Cox regression analysis of 165 LT recipients with HCC between 2014 and 2019 in Huashan hospitals affiliated to Fudan university. The inclusion criteria: 1) histologically proven to be HCC; 2) without extrahepatic metastasis. The exclusion criteria: 1) concurrent malignancy; 2) died within 1 month; 3) other malignancies; 4) without a complete clinicopathologic records. The association of the risk score with recurrence and response to targeted therapy was assessed.
Results and Discussion: The mean follow-up period was 20 months, ranging from 1 to 60 months. A total of 165 cases were included. Overall patient and recurrence-free survivals were 92%, 84%, 77% and 86%, 74%, and 67% at 1-, 2-, and 3-years, respectively. 35 patients experienced tumor recurrence and the median disease-free survival (DFS) was 14 months. Multivariate predictors of recurrence included preoperative AFP (>200ng/ml hazard ratio [HR] 2.76), preoperative GGT(> 96U/L [HR] 2.76) and exceeding Hangzhou criteria (HR 1.98). Thus, AFP_GGT_Hangzhou (AGH) score was established based on the combined scores of AFP, GGT, and Hangzhou criteria. Patients meet at least two factors, defined as high risk, one as medium risk and none as low risk(Figure 1). AGH score, incorporating only known radiographic and laboratory parameters, had improved accuracy in predicting HCC recurrence (C statistic 0.74) compared with both Milan (C statistic 0.63) and UCSF (C statistic0.64) criteria alone. Furthermore, AGH score was the only independent risk factor affecting OS and DFS. AT last, only in the high risk group of HCC patients, can we found an improvement on DFS for taking adjuvant targeted treatment (sorafenib[P=0.043] or lenvatinib[P=0.027] vs. control group, Figure 2). Conclusion: AGH score may have the potential to serve as a predictor of recurrence and beneficiaries from targeted drug therapy in HBV related HCC patients following LT.