Predictors, Presentation, and Treatment Outcomes of Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Large Single Center Experience

Background: Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT. Methods: Patients with recurrent HCC after LT between January 1996 and December 2017 were retrospectively reviewed. Results: Of 711 patients, 96 (13.5%) patients had post-LT HCC recurrence. The median time to recurrence was 17.1 months, and the median survival was 10.1 months. Initial recurrence was more often in the graft (34.4%), and most (60.4%) had multiple recurrent lesions, and 26% were in multiple sites. In multivariate analysis, factors associated with shorter survival were poorly differentiated histology in explant (Hazard ratio [HR] = 1.96; p = 0.027), bilirubin >= 1.2 mg/dL (HR = 2.47; p = 0.025), and albumin <3.5 mg/dL (HR = 2.13; p = 0.014) at recurrence, alpha-fetoprotein at recurrence >= 1000 ng/mL (HR = 2.96; p = 0.005), and peritoneal disease (HR = 3.20; p = 0.022). There was an increased survival in patients exposed to sirolimus (HR = 0.32; p < 0.0001). Conclusions: Recurrent HCC after LT is often in extrahepatic sites with a decreased survival in those with poorly differentiated explant pathology, high bilirubin, low albumin, marked elevation of alpha-fetoprotein at recurrence, and peritoneal recurrence. Sirolimus-based immunosuppression may provide benefit.