A Preliminary Predictive Model of Post-Transplant Tumor Recurrence in Hepatitis B Virus Associated Hepatocellular Carcinoma-Epidemiological and Therapeutic Implications

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide with hepatitis B virus (HBV) as the most important etiological agent. Unfortunately, the outcome of medical management of HBV related HCC is abysmal and post-transplant tumor recurrence represents a major challenge. However, a robust clinical predictor of disease recurrence in HBV mediated HCC is yet to be established despite several evidences illustrating multiple causative factors. Aim: Here we report a preliminary model that predicted the probability of post-transplant tumor recurrence in patients presenting with HBV related HCC and opting for living donor liver transplantation (LDLT). Methods: Our study prospectively recruited 67 quantitative HBV DNA positive HCC patients and 71 quantitative HBV DNA negative HCC patients, all with documented evidences of chronic HBV infection. A linear model analysis based on minimum Akaike's Information Criterion (AIC) values was computed. This generated a statistical inference about the causal relationship between different pre- and post-transplant clinicopathological variables of the study population and pre-transplant tumor recurrence of HBV related HCC. Additionally, a Cox's proportional hazard modeling showing independent predictors of post transplant tumor recurrence was also illustrated. Results: Several combinations of linear models were assessed and significant parameters like age (b=0.06, p=0.02), alpha-fetoprotein (b=0.02, p=0.01) levels, HBV DNA (b=0.05, p=0.03) levels, total tumor burden (b=0.08, p=<0.001) and Model for End-Stage Liver Disease (MELD) score (b=0.07, p=0.04) predicted probability of post-transplant tumor recurrence. Multivariable analysis through Cox proportional hazard modeling further depicted HBV DNA and AFP levels as predictors of post transplant tumor recurrence in HBV related HCC. Additionally, a novel algorithm proposed a differentiation of patients opting for living donor liver transplantation (LDLT) into low, intermediate and high risk categories for developing recurrence of the disease. Conclusions: The outcome of our study might facilitate improved prognostication, risk stratification and better clinical management of patients with HBV related HCC.