Abstract:

AIM: To explore the relationship between surface costimulatory molecules and T lymphocyte subsets in peripheral blood of HBV infected patients and HBV-DNA, and its role in the development of HBV infection, especially in severe liver failure（such as ACLF）. METHODS: 120 cases with chronic HBV infection which were selected from the first affiliated hospital The First Affiliated Hospital,School of Medicine,Zhejiang University and Zhejiang Province Youth Hospital, 60 cases with chronic hepatitis B（CHB group）, 30 cases with hepatitis B-induced livercirrhosis（LC group）, 30 cases with acute-on-chronic liver failure（ACLF group）. The CHB group was further divided into the HBeAg positive group(n=30) and the HBeAg negative group(n=30) , 30 healthy subjects served as control group.The peripheral blood CD+4 and CD+8T cells programmed cell death (PD-1),cytotoxic T lymphocyte associated antigen-4(CTLA-4),T cell immunoglobulin mucin-3 (Tim3),T lymphocyte (CD+3) ,T helper T cells (CD+4) and inhibition of T cells (CD+8) level were detectd by flow cytometry.The HBV-DNA load of each group was detected by PCR. Pearson was used to analyze the correlation. RESULTS: The expressions of CD+4CTLA-4 and CD+8CTLA-4 in HBV infected patients were lower than those in the control group, and the expressions of CD+4CTLA-4,CD+8CTLA-4,CD+8PD1,CD+4Tim3 and CD+8Tim3 in CHB group were all higher than those in the LC group and the ACLF group(P<0.05).The expression of CD+3,CD+4and CD+4/CD+8 in patients with HBV infection was lower than that in control group, and the expressions of CD+8 was higher in CHB group than those in LC group and ACLF group , CD+8expressions were lower than those in the LC group and ACLF group. The level of HBV-DNA in CHB group was higher than that in LC group and ACLF group.All were statistically significant (P<0.05). The expression of CD+4CTLA-4,CD+8CTLA-4,CD+3,CD+4 and CD+4/CD+8 in HBeAg-positive group was lower than that in HBeAg-negative group, while the expression of CD+4PD1,CD+8PD1,CD+4Tim3,CD+8Tim3 and CD+8 in HBeAg-positive group was higher than that in HBeAg-negative group (P<0.05).In patients infected with HBV, HBV-DNA is positively correlated with CD+8PD1, CD+8Tim3 (P<0.05), but not with CD+4CTLA-4,CD+8CTLA-4,CD+4Tim3,CD+4PD1,CD+3,CD+4 and CD+8(P>0.05).Compared with the LC group, the expression level of CD+4PD-1 in the ACLF group was increased, while the expression level of CD+8CTLA-4  was decreased. CONCLUSION: Peripheral blood T-lymphocyte surface co-stimulatory molecules and T-lymphocyte subpopulation proportion are associated with the development of HBV infection, especially the progression of severe disease (such as ACLF), which has certain clinical application value for the curative effect and prognosis of the disease.

Key words: HBV infection, co-stimulatory molecules, T-lymphocyte subsets, HBV-DNA