Impaired Pre-transplant Cholesterol Metabolism Predicts Tumor Recurrence After Liver Transplantation For Hepatocellular Carcinoma

Background The 5-year tumor recurrence rate ranges from 20.0% to 57.8% after liver transplantation(LT)for hepatocellular carcinoma.In order to improve the LT outcome,precise recurrence risk prediction is necessary.Cholesterol metabolism takes an important role in regulating proliferation,energy supply and signal transduction of malignant tumors such as hepatocellular carcinoma(HCC).We aim at exploring the tumor recurrence risk predicting capacity of pre-transplant circulating clinical cholesterol metabolism-related biomarkers in liver transplantation for HCC.Method Current research enrolled clinical and pathological data as well as follow-up information of 209 HCC-related LT recipients.Retrospective analysis was conducted to explore the correlation between pre-transplant plasma cholesterol metabolic status and post-transplant tumor recurrence after LT.Survival analysis was carried out based on the pre-transplant cholesterol metabolism-related factors and tumor recurrence,important perioperative clinical biomarkers and commonly-used transplantation criteria were also enrolled to evaluate the recurrence risk prediction ability.We aim at establishing cholesterol relevant prognostic model to optimize existing tumor recurrence prediction system for HCC-related LT.Results The univariate analysis of cholesterol biomarkers and prognosis showed that triglyceride(TG),total cholesterol(TC)and low-density protein-cholesterol/high-density protein-cholesterol(LDL-C/HDL-C)ratio significantly elevated in recipients with tumor recurrence after LT.Then we established a cholesterol related index called TLH index(TLH index=TC*LDL-C/HDL-C).The AUROC of TLH index was 0.67(p<0.001).The 3-year tumor recurrence free survival(RFS)rate was significantly higher in low TLH group(low TLH group vs high TLH group=75.5% vs 43.5%,p<0.001).The multivariate COX regression analysis showed that pre-transplant plasma TLH index(p<0.001)and Hangzhou criteria(p<0.001)were independent risk factors of tumor recurrence after LT for HCC patients.When combined with TLH index,patients within Hangzhou criteria were subdivided into two groups with significantly different 3-year RFS rate: low TLH within Hangzhou criteria vs high TLH within Hangzhou criteria=90.1% vs 76.0%(p<0.001).Conclusion Impaired cholesterol metabolism contributes to increased tumor recurrence risk in liver transplantation for HCC patients.Based on cholesterol metabolism relevant biomarkers,we established TLH index which effectively predicted post-transplant tumor recurrence.When combined with Hangzhou criteria,this index might be useful to optimize candidate selection in liver transplantation for HCC patients.