Donor graft steatosis influences immunity to hepatitis C virus and allograft outcome after liver transplantation.

Background. Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is universal, often with accelerated allograft fibrosis. Donor liver steatosis is frequently encountered and often associated with poor early postoperativeoutcome.Theaimofthisstudywastotestthehypothesisthatallograftsteatosisaltersimmuneresponses to HCV and self-antigens promoting allograft fibrosis. Methods.Forty-eightHCVOLTrecipients(OLTr)wereenrolledandclassifiedbasedonamountofallograftmacrovesicular steatosis at time of OLT. Group 1: no steatosis (0%–5% steatosis, n21), group 2: mild (5%–35%, n16), and group 3: moderate (35%, n11). Cells secreting interleukin (IL)-17, IL-10, and interferon gamma (IFN- )i n responsetoHCVantigenswereenumeratedbyEnzymeLinkedImmunospotAssay.Serumcytokinesweremeasuredby Luminex, antibodies to Collagen I, II, III, IV, and V by ELISA. Results. OLTr of moderate steatotic grafts had the highest incidence of advanced fibrosis in protocol 1 year post-OLT biopsy (10.8% vs. 15.8% vs. 36.6%, r0.157, P0.05). OLTr from groups 2 and 3 had increased HCV-specific IL-17 (P0.05) and IL-10 (P0.05) with reduced IFN- (P0.05) secreting cells when compared with group 1. This was associated with increase in serum IL-17, IL-10, IL-1, IL-6, IL-5, and decreased IFN-. In addition, there was development of antibodies to Collagen I, II, III and V in OLTr with increased steatosis (P0.05). Conclusion. The results demonstrate that allograft steatosis influences post-OLT HCV-specific immune responses leading to an IL-17 T-helper response and activation of humoral immune responses to liver-associated self-antigens that may contribute to allograft fibrosis and poor outcome.