Adjuvant Adenovirus-Mediated Delivery of Herpes Simplex Virus Thymidine Kinase Administration Improves Outcome of Liver Transplantation in Patients with Advanced Hepatocellular Carcinoma

Abstract Purpose: Previous poor results of liver transplantation (LT) have been confirmed in patients with advanced hepatocellular carcinoma (HCC). Adenovirus-mediated delivery of herpes simplex virus thymidine kinase (ADV-TK) therapy is an established adjuvant treatment in cancer, and we evaluated its potential as an adjuvant treatment for HCC patients who underwent LT. Experimental Design: Forty-five HCC patients with tumors >5 cm in diameter participated in the study over a follow-up period of 50 months. Among these patients, 22 received LT only, and 23 received LT combined with ADV-TK therapy. All HCC patients enrolled in this study had tumors >5 cm in diameter and no metastasis in lungs or bones was detected by computed tomography or magnetic resonance imaging scans. Results: The recurrence-free survival and the overall survival in the LT plus ADV-TK therapy group were 43.5% and 69.6%, respectively, at 3 years; both values were significantly higher than those in the LT-only group (9.1% and 19.9%, respectively). In the nonvascular invasion subgroup, overall survival was 100% and recurrence-free survival was 83.3% in the patients receiving LT plus ADV-TK, significantly higher than the patients receiving LT only. Conclusions: HCC patients with no vascular invasion could be selected for LT followed by adjuvant ADV-TK therapy, regardless of intrahepatic huge or diffuse tumor. We propose that the current criteria for LT based on tumor size may be expanded if accompanied by ADV-TK therapy due to improved prognosis.