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.
BACKGROUND:Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is universal, often with accelerated allograft fibrosis. Donorliver 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.
Authors: A K Chui; L W Shi; A R Rao; D J Verran; D Painter; D Koorey; G W McCaughan; A G Sheil Journal: Transplant Proc Date: 2000-11 Impact factor: 1.066
Authors: R M Ghobrial; R Steadman; J Gornbein; C Lassman; C D Holt; P Chen; D G Farmer; H Yersiz; N Danino; E Collisson; A Baquarizo; S S Han; S Saab; L I Goldstein; J A Donovan; K Esrason; R W Busuttil Journal: Ann Surg Date: 2001-09 Impact factor: 12.969
Authors: Brian B Borg; Anil Seetharam; Vijay Subramanian; Haseeb Ilias Basha; Mauricio Lisker-Melman; Kevin Korenblat; Christopher D Anderson; Surendra Shenoy; William C Chapman; Jeffrey S Crippin; Thalachallour Mohanakumar Journal: Liver Transpl Date: 2011-07 Impact factor: 5.799
Authors: G V Papatheodoridis; S Davies; A P Dhillon; R Teixeira; J Goulis; B Davidson; K Rolles; G Dusheiko; A K Burroughs Journal: Transplantation Date: 2001-08-15 Impact factor: 4.939
Authors: P W Baron; D Sindram; D Higdon; D N Howell; M R Gottfried; J E Tuttle-Newhall; P A Clavien Journal: Liver Transpl Date: 2000-07 Impact factor: 5.799
Authors: E J Gane; N V Naoumov; K P Qian; M U Mondelli; G Maertens; B C Portmann; J Y Lau; R Williams Journal: Gastroenterology Date: 1996-01 Impact factor: 22.682