De Novo Hepatocellular Carcinoma Among Liver Transplant Registrants in the Direct Acting Antiviral Era

The risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) receiving direct acting antivirals (DAAs) has been debated. This study aims to describe the incidence of HCC among patients listed for liver transplantation (LT) in the DAA era. Individuals with cirrhosis listed for LT from January 2003 to December 2015 were identified using the Scientific Registry for Transplant Recipients database. Patients with HCC at listing or HCC exception within 180 days were excluded. Patients were divided into three eras based on listing date: eras 1 (2003-2010), 2 (2011-2013), and 3 (2014-2015). Incidence rates of HCC were calculated by era and compared using incident rate ratios (IRRs). The association between HCC and listing era was evaluated using Cox regression and competing risk analyses, the latter considering death and LT as competing events. Of the 48,158 eligible wait-list registrants, 3112 (6.5%) received HCC exceptions after a median of 493 days. In 20,039 individuals with HCV, the incidence of HCC was 49% higher in era 3 versus era 1 (IRR 1.49, 95% confidence interval [CI] 1.24-1.79). In multivariate analysis, those in era 3 had a higher hazard of HCC compared with era 1 (hazard ratio 1.22, 95% CI 1.01-1.48). However, in multivariable competing risks analysis, with death and LT considered as competing events for de novo HCC, era was no longer associated with HCC (subdistribution hazard ratio 0.83, 95% CI 0.69-1.00). Conclusion: In this large population-based cohort of LT registrants, the incidence of HCC among HCV patients has increased in the DAA era. Competing risks analysis suggests that this may be explained by changes in rates of LT and wait-list mortality in the HCV population during this time. (Hepatology 2018; 00:000-000).