Impact of Baseline Steatosis and Severity of Ischaemia-Reperfusion Injury in Predicting HCV Recurrence Post Liver Transplantation

Abstract

Introduction: Recurrent HCV (rHCV) infection is universal post-transplantation and is associated with significant morbidity and mortality. HCV recurrence is influenced by a combination of donor, recipient, viral and immunosuppressive factors. Methods: We hypothesised that baseline steatosis and the severity of ischaemia-reperfusion (IR) injury can predict slow and rapid fibrosis (F>2) progression at 12 months. IR injury and steatosis was graded as none (0) to severe (3). Predictive ability was assessed using the area under the curve generated by receiver operator characteristic analysis (AUROC). Results: During January 2000 and January 2011, 303 adult patients (> 18 years) with chronic HCV underwent primary liver transplantation at King’s College Hospital NHS Foundation Trust, London. Of these 303 patients, 141 had an IR liver biopsy performed. Median age at transplant was 53 years (19-67), median donor age was 46 years (15-85). Median IR grade was 1(0-3) and median grade of steatosis was 0(0-3). Median peak AST was 1218 IU/ml (236-5045). Patients were followed up for 46 months (4-143). Patients were then divided into groups according to the result of their 12 month biopsy result (slow fibrosis progression rate - F<2 Ishak; fast fibrosis progression rate - F≥2). Patients with slow fibrosis progression at 12 months were male, had younger donors, and a longer time to F≥4 post-LT (p<0.04). Moderate/severe IR injury was a poor predictor of fast fibrosis progression (AUROC 0.54, 95% CI 0.36-0.71, p=0.67), although the presence of steatosis along with moderate/severe IR injury was a sensitive predictor of F≥2 at 12 month (0.79, 0.66-0.89, p<0.0001). Patients with the combination of steatosis and moderate/severe IR injury were more likely to develop F≥2 at 12 months (86% vs. 30%, p<0.0001). Conclusion: The combination of steatosis and moderate/severe degree of IR injury appears to correctly identify patients with rapid fibrosis of rHCV in the post-transplant setting.