TY - JOUR
T1 - Donor graft steatosis influences immunity to hepatitis C virus and allograft outcome after liver transplantation
AU - Subramanian, Vijay
AU - Seetharam, Anil B.
AU - Vachharajani, Neeta
AU - Tiriveedhi, Venkataswarup
AU - Angaswamy, Nataraju
AU - Ramachandran, Sabarinathan
AU - Crippin, Jeffrey S.
AU - Shenoy, Surendra
AU - Chapman, William C.
AU - Mohanakumar, Thalachallour
AU - Anderson, Christopher D.
PY - 2011/12/15
Y1 - 2011/12/15
N2 - 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 postoperative outcome. The aim of this study was to test the hypothesis that allograft steatosis alters immune responses to HCV and self-antigens promoting allograft fibrosis. METHODS.: Forty-eight HCV OLT recipients (OLTr) were enrolled and classified based on amount of allograft macrovesicular steatosis at time of OLT. Group 1: no steatosis (0%-5% steatosis, n=21), group 2: mild (5%-35%, n=16), and group 3: moderate (>35%, n=11). Cells secreting interleukin (IL)-17, IL-10, and interferon gamma (IFN-γ) in response to HCV antigens were enumerated by Enzyme Linked Immunospot Assay. Serum cytokines were measured by 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%, r=0.157, P<0.05). OLTr from groups 2 and 3 had increased HCV-specific IL-17 (P<0.05) and IL-10 (P<0.05) with reduced IFN-γ (P<0.05) secreting cells when compared with group 1. This was associated with increase in serum IL-17, IL-10, IL-1β, IL-6, IL-5, and decreased IFN-γ. In addition, there was development of antibodies to Collagen I, II, III and V in OLTr with increased steatosis (P<0.05). 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.
AB - 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 postoperative outcome. The aim of this study was to test the hypothesis that allograft steatosis alters immune responses to HCV and self-antigens promoting allograft fibrosis. METHODS.: Forty-eight HCV OLT recipients (OLTr) were enrolled and classified based on amount of allograft macrovesicular steatosis at time of OLT. Group 1: no steatosis (0%-5% steatosis, n=21), group 2: mild (5%-35%, n=16), and group 3: moderate (>35%, n=11). Cells secreting interleukin (IL)-17, IL-10, and interferon gamma (IFN-γ) in response to HCV antigens were enumerated by Enzyme Linked Immunospot Assay. Serum cytokines were measured by 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%, r=0.157, P<0.05). OLTr from groups 2 and 3 had increased HCV-specific IL-17 (P<0.05) and IL-10 (P<0.05) with reduced IFN-γ (P<0.05) secreting cells when compared with group 1. This was associated with increase in serum IL-17, IL-10, IL-1β, IL-6, IL-5, and decreased IFN-γ. In addition, there was development of antibodies to Collagen I, II, III and V in OLTr with increased steatosis (P<0.05). 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.
KW - Allograft Steatosis
KW - Fibrosis
KW - Hepatitis C
KW - Liver transplantation
KW - Recurrence
UR - http://www.scopus.com/inward/record.url?scp=81855170240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81855170240&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e318235a1ab
DO - 10.1097/TP.0b013e318235a1ab
M3 - Article
C2 - 22011763
AN - SCOPUS:81855170240
SN - 0041-1337
VL - 92
SP - 1259
EP - 1268
JO - Transplantation
JF - Transplantation
IS - 11
ER -