What Is the Optimal Bridging Therapy for Patients with Hepatitis C-associated Hepatocellular Carcinoma Awaiting Liver Transplant? An Analysis of the United States HCC Liver Transplantation Consortium

Abstract

Introduction: Patients with hepatitis C (HCV)-associated hepatocellular carcinoma (HCC) often receive bridging therapy in the form of liver-directed therapy (LDT) while awaiting liver transplant (LT). The optimal modality of LDT, with respect to both cancer outcomes and response to direct-acting antiviral (DAA) therapy, remains unknown. Methods: The United States HCC Liver Transplantation Consortium was queried for patients with primary HCV-associated HCC within Milan criteria who completed DAA therapy and underwent LT. Primary outcomes were HCC recurrence-free survival (RFS) and overall survival (OS). Secondary outcome was sustained virologic response (SVR) as indicator of efficacy of DAA therapy. Results: Of 857 patients, 753 met inclusion criteria. LDT consisted of radiofrequency ablation (RFA,13.3%,N=100), transarterial chemoembolization (TACE,44.1%,N=332), yttrium-90 (Y90,4.8%,N=36), and stereotactic body radiation therapy (SBRT,2.9%,N=22). Eighty-one(10.8%) patients received no LDT and 182(24.2%) received multiple modalities. SBRT patients had the highest 5-year RFS(100%) followed by those receiving TACE(94%), Y90(91.4%), RFA(89.9%), and multiple therapies(88.2%) (p=0.048, Figure 1A). OS was higher among patients who received SBRT, but not statistically significant (p=0.685, Figure 1B). SVR rate was lower among radiation-based therapy groups (Y90 73.5%, SBRT 78.9%, others≥88%; p=0.046). Conclusions: In a homogeneous population of HCV-associated HCC patients within Milan criteria who received bridging therapy while awaiting LT, SBRT was associated with increased RFS and trended towards increased OS. However, radiation-based therapy was associated with decreased efficacy of DAA as measured by lower SVR rates. The optimal choice of bridging therapy to liver transplant must balance oncologic and virologic outcomes, but these findings seem to favor SBRT.