Expression Of The Programmed Death-1 In HBV-associated Acute-on-chronic Liver Failure

Characteristics of PD-1/PD-L1 expression in HBV-associated acute-on-chronic liver failureObjectiveTo investigate the expression pattern of programmed death-1(PD-1) and its ligand (PD-L1) in HBV-associated acute-on-chronic liver failure(HBV-ACLF) patients and the relationship between PD-1 expression and the prognosis of HBV-ACLF.To elucidate the impacts of PD-1/PD-L1 on the progression of HBV-ACLF. Methods60 HBV-ACLF,15 liver cirrhosis(LC) and 15 healthy control(HC) were enrolled in this study.For HBV-ACLF,subjects were followed up for one month at least and venous blood was colleted every week.Clinical parameters were collected accordingly, including HBV viral load,ALT,AST,TBIL,PA,WBC et al.We analyzed the expressions of PD-1,CD95,CD45RA,CCR7,Perforin,granzyme A,granzyme B, CD107a on CD8~+T lymphocytes and the expression of PD-L1 on monocytes in peripheral blood by using flow cytometry.CBA(Cytometric Bead Array) kit was employed to measure the concentrations of IL-2(interleukin-2),IL-4,IL-6,IL-10,TNF-αand IFN-γin serum.Paraffin-embedded liver sections from HBV-ACLF liver tissue(10 cases),biopsies of LC patients(10 cased),and healthy donor liver sections(6 cases) were used for immunohistochemical staining,including CD4,CD8,PD-1 and PD-L1.ResultsThe PD-1 expression in HBV-ACLF patients(17.31%±11.28%) was significantly elevated compared with those in HC(11.18%±5.38%) and LC subjects(5.96%±4.19%). PD-1 also up-regulated in the group whose meld score≥20(20.98%±12.28%),compared with＜20 group(13.61%±8.23%).(P＜0.05).PD-1 expression was lower in improved group(12.89%±7.18%) than that in non-improved group(21.19%±11.21%).(P＜0.05), and increased from early stage(13.27%±7.2%),middle stage(18.86%±10.31%) to late stage(29.51%±19.59%).(P＜0.05).Moreover,PD-L1 expression on monocytes was positively correlated with disease progression.(P＜0.05) Both PD-1 and CD95 expressions were higher in dead group than those in improved and non-improved groups.Perforin,granzymes and CD107a expressions on CD8~+T cells significantly increased in dead group compared with those in improved and non-improved groups(P＜0.05).However,PD-1 expressions on these cells were lower,compared with normal persons.ConclusionsThe expression of PD-1 in HBV-ACLF patients was positively correlated with disase progression.PD-1 expression was increased in portal area and PD-L1 was increased on hepatocytes in liver section of HBV-ACLF patients.For HBV-ACLF patients,the PD -1 expression on effector CD8~+ T cells was lower than those in other cells,accounting for the failure in controlling immune injury in liver.