Acute cellular rejection in hepatitis C recipients following liver transplantation in the era of direct-acting antivirals: chronological analysis of the United Network for Organ Sharing database

Introduction Interferon (IFN) treatment for liver transplant (LT) recipients with hepatitis C virus (HCV) increases acute cellular rejection (ACR) and worsens graft and patient survival. It is unknown if direct-acting antivirals (DAAs) affect rejection rates or post-transplant survival. Method The United Network for Organ Sharing STAR files of December 2017 (n = 25,916) were analyzed. Results Compared with non-HCV-LT, HCV-LT survival was worse in the IFN-era (2007-2008) and IFN+DAA-era (2011), but not in the DAA-era (2014-2015). ACR6m rate has been less frequent in newer eras and was lower in HCV-LT than in non-HCV-LT in both the DAA-era (6.9% vs. 9.3%, P < 0.001) and in the IFN+DAA-era (8.8% vs. 11.8%, P = 0.001), but not in the IFN-era (10.8% vs. 11.0%, P = 0.39). HCV-LT recipients who had ACR6m had worse 2-year survival than those without ACR6m, in the IFN-era (80.0% vs. 88.4%, P < 0.0001) and in the IFN+DAA-era (81.4% vs. 89.2%, P < 0.01) but not in the DAA-era (90.4% vs. 93.2%, P = 0.085). Cox proportional hazard model identified ACR6m as independent risk factor for mortality in HCV-LT in the IFN-era (HR = 1.88, P <= 0.001) and in the IFN+DAA-era (HR = 1.84, P = 0.005), but not in the DAA-era (P = n.s.). Conclusions Two-year survival of HCV-LT recipients were significantly better in the DAA-era; these were associated with reduced rate and impact of ACR6m.