A recent study published in Engineering has shed light on the impact of alcoholic liver disease (ALD) on post-transplant hepatitis B virus (HBV) reactivation and survival outcomes in patients with hepatocellular carcinoma (HCC). The research, conducted by a team of medical experts from various institutions in China, highlights the significant role of ALD in exacerbating HBV reactivation and worsening surgical outcomes in liver transplant recipients with a history of HBV infection.

The study retrospectively analyzed a cohort of 453 liver transplant recipients with HBV-related HCC, of whom 113 had concurrent pre-transplant diagnoses of ALD and HBV infection, while the remaining 340 had HBV infection alone. Using propensity score matching (PSM) and sensitivity analyses, the researchers assessed the influence of ALD on surgical outcomes. They found that patients with ALD had a significantly higher risk of HBV reactivation and liver metastasis compared to those without ALD. Specifically, the five-year HBV reactivation-free survival rate was 74.9% in the ALD group, compared to 85.4% in the non-ALD group. Similarly, overall survival (OS) and tumor recurrence-free survival (RFS) were also lower in the ALD group, with rates of 56.2% and 47.8%, respectively, compared to 70.5% and 63.3% in the non-ALD group.

The researchers employed a machine learning approach to predict post-transplant HBV reactivation, identifying the surv.cforest model as the optimal predictor. This model achieved an area under the receiver operating characteristic (AUC) curve of 0.914 in internal validation and 0.884 in external validation, outperforming the previously published Cox model (AUC = 0.78). The SHapley Additive ExPlanation (SHAP) algorithm was used to rank features and interpret the model, revealing that metabolic parameters such as total cholesterol (TC), high-density lipoprotein (HDL), and triglyceride (TG) levels were key determinants of HBV reactivation risk.

To further stratify patients based on their risk of HBV reactivation, the researchers developed the Alcohol-Modified HBV Reactivation Index (AMBRI). Patients were divided into three risk subgroups: low risk (AMBRI < 45), intermediate risk (AMBRI 45–90), and high risk (AMBRI ≥ 90). The study found that intermediate- and high-risk groups exhibited significantly worse OS and RFS compared to the low-risk group. Notably, the presence of ALD was strongly correlated with higher AMBRI scores, indicating a greater likelihood of adverse outcomes.

The findings of this study underscore the importance of considering ALD as a significant risk factor for HBV reactivation in liver transplant recipients with HBV-related HCC. The researchers recommend intensified surveillance and enhanced HBV treatment regimens, particularly for recipients with a pre-transplant history of ALD. They also suggest that future clinical guidelines should incorporate metabolic parameters and ALD-related clinical indicators to improve risk prediction and management in this patient population.

This study provides valuable insights into the complex interplay between ALD and HBV reactivation in liver transplant recipients, highlighting the need for personalized risk assessment and management strategies to optimize clinical outcomes.

Ethical approval for the HBV reactivation cohort was obtained from the Ethics Committee of two centers (Shulan (Hangzhou) Hospital and The First Affiliated Hospital, Zhejiang University School of Medicine), consistent with prior research (approval IDs: No. 2020-510 and No. KY2021014).

The paper “Post-Transplant Hepatitis B Virus Reactivation and Survival in Hepatocellular Carcinoma Patients with Alcoholic Liver Disease,” is authored by Renyi Su, Huigang Li, Xuanyu Zhang, Linping Cao, Zhe Yang, Jinyan Chen, Shusen Zheng, Xiao Xu, Di Lu, Xuyong Wei. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.03.016. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.