Abstract
Hepatitis C virus (HCV) recurrence following liver transplantation (OLT) is associated with increased allograft fibrosis. Severe donor graft steatosis results in poor early post-operative outcomes but steatosis resolves within 3 weeks. Goal of this study is to characterize the role of donor liver steatosis on HCV immunity, fibrosis and outcome post OLT. Methods: HCV OLT recipients were enrolled at 1 year. Based on donor steatosis, grafts were divided into: Group 1-No steatosis (0-5% steatosis, n=18), Group 2 - Mild (5-33% steatosis, n=15), Group 3 - moderate (>33% steatosis, n=10). Mononuclear cells were stimulated with HCV antigens, and IL-17 and IL-10 cells were enumerated by ELISpot. Serum antibodies (abs) to Collagen (Col) 3 were measured by ELISA. Results: Patient demographics were similar in all groups. Group 3 OLT had a higher incidence of fibrosis (Batts Ludwig grades 3 or 4) when compared to groups 2 and 1 (93%, 34%, 15%, p<0.05). Group 3 demonstrated higher HCV specific IL17 (10±2.1, 12.2±5.2, 23±3.3 spots per million cells (spm) p<0.05) and IL10 secreting cells (107±23.1, 259.6±30.5, 402.3±37.3 spm, p<0.05). Groups 2 and 3 also had higher abs to Col 3 (11±1.1, 13±1.7, 17±1.5 µg/ml, p=0.05). Patient survival at 2 years was 100%, 95% and 84% among the three groups. Conclusion: Donor graft steatosis significantly influenced immune responses to HCV following OLT leading to increased IL17 and IL10 as well as increased incidence of autoimmunity and poorer outcome.