HBV reactivation and its metabolomic profile after liver transplantation for hepatocellular carcinoma in non-alcoholic steatohepatitis.

[OBJECTIVE] The role of non-alcoholic steatohepatitis (NASH) in hepatitis B virus (HBV) reactivation following liver transplantation for hepatocellular carcinoma (HCC) remains unclear, and the metabolic differences between patients with NASH and those with HBV reactivation are also yet to be elucidated. This study is to investigate the impact of NASH on HBV reactivation risk and prognosis following liver transplantation for HCC, and to develop a predictive model and identify therapeutic targets.

[METHODS] This study included 274 patients who underwent liver transplantation for HCC. The HBV reactivation status of patients with NASH was analyzed, and the metabolic characteristics of peripheral blood were examined to compare NASH and non-NASH patients with or without HBV reactivation.

[RESULTS] The HBV reactivation free survival was better in non-NASH patients (P<0.0001). Furthermore, NASH patients with HBV reactivation had worse recurrence-free survival (RFS) than non-NASH patients with HBV reactivation (P=0.016). In contrast, the RFS of NASH patients without HBV reactivation was comparable to that of non-NASH patients without HBV reactivation (P=0.810). Subsequently, we constructed a model to predict HBV reactivation by incorporating 7 clinical indicators using the Least Absolute Shrinkage and Selection Operator-Cox (LASSO-Cox) approach. The area under the receiver operating characteristic curve (AUROC) values for predictions at 500, 1,000, and 1,500 d were 0.759, 0.809, and 0.814, respectively. Finally, metabolic pathway analysis identified key pathways involved in HBV reactivation, and glutamine was found to be an independent protective factor against HBV reactivation following liver transplantation for HCC.

[CONCLUSIONS] NASH patients are more prone to HBV reactivation following liver transplantation for HCC and exhibit worse recurrence-free survival. Glutamine may serve as a potential therapeutic target or predictive biomarker for HBV reactivation.