The Changes And Clinical Significance Of T Helper Lymphocyte Subsets And Inflammatory Factors Of The Patients With HBV-associated Subacute-on-chronic Liver Failure

Background In China, as a major cause of Subacute-on-chronic liver failure（SACLF）, CHB accounted for80%of all SACLF etiology. Currently it considered that theoutcome of HBV infection is influenced by many factors, and the host’s immune played asignificant role, and the cytokines also played a key role in regulating the immune response.According to the secretion of cytokines, T helper cells were divided into: Th0, Th1, Th2,Th3, Studies suggested that in viral hepatitis infection, Th1cells favored the removal of thevirus while Th2cells were primarily associated with tissue damage and chronic. Recently,a new effecter Th17belonging to CD4+subsets rewritted the classic Th1/Th2cell reactionmode, which was a strong pro-inflammatory factor characterized by secretion ofinterleukin17. In2005,Kim et al found IL-32,which produced by T cells, NK cells,monocytes, epithelial cells.Further studies showed it could promote the characteristics ofinflammatory cytokines. IL-10as a strong immune and inflammatory inhibitor wasproduced by Th2cells, macrophages, dendritic cells （Dendritic cells, DC）, and B cells, etc.It could reduce the activity of T cells and then reduced the immune response, making thebody to get rid of the virus diminished capacity. Above cells and cytokines had beenreported t in CHB, whether the dynamic changes of the above cells and cytokines in thehepatitis B-related SACLF （HBV-SACLF）in different stages and the correlation of theirbetween ALT had not been reported.Objective To investigate the expression，dynamic change and clinical significance ofTh1、Th2、Th17in peripheral blood and IL-32、IL-10in serum of the patients with SACLF during different periods.Methods Detected the ratio of Th1、Th2、Th17from peripheral blood cells in38HBV-SACLF patients,46pre-liver failure patients,20CHB patients and20health adultsby fluorescence-activated cell sorter; compared the above indicators among the four groups;observed dynamic changes of Th1、Th2and Th17during the nonage, metaphase andadvanced stage of HBV-SACLF; studied the expression level changes of Th1, Th2, ofTh17in infection group and non-infected group, survival group and non-survival group;analyzed the correlation of Th1, Th2,Th17and ALT. Detected the expression ofIL-32,IL-10from the serum of38HBV-SACLF patients,46Pre-liver failure patients,20CHB patients and20health adults by ELISA; observed dynamic changes of IL-32,IL-10during the nonage, metaphase and advanced stage of HBV-SACLF.Results1. The ratios of Th1, Th2,Th17on peripheral blood cells in38HBV-SACLF patients,46Pre-liver failure patients,20CHB patients and20health adults were as follows:â‘ Th1：（22.58±3.86）%、（20.80±3.32）%、（5.23±1.51）%、（6.45±1.27）%;the ratios of Th1in HBV-SACLF group were significantly higher than CHB group and control group（P₂=0.04，P3=0.032）.â‘¡T h2：（1.73±0.64）%、（1.03±0.34）%、（6.15±0.97）%、（1.98±0.46）%; the ratios of Th2in HBV-SACLF group were significantly lower than CHB group andcontrol group（P₂=0.007，P3=0.041）③Th17：（3.48±0.80）%、（3.61±1.20）%、（1.09±0.4）%、（0.72±0.11）%,;the ratios of Th17in HBV-SACLF group were significantly higherthan CHB group and control group（P₂=0.003，P3<0.001）.2. The ratios of Th1, Th2and Th17cells in the nonage, metaphase and advanced stageof38HBV-SACLF patients were as follows:â‘ T h1：（26.11±5.19）%、（22.45±4.06）%、（18.33±3.21）%;The ratios of Th1decreased gradually, There were also significantdifferences among the three periods（P1=0.001, P₂=0.004）.â‘¡Th2：（0.95±0.20）%、（1.66±0.41）%、（2.54±1.03）%ï¼›The ratios of Th2increased gradually, There were alsosignificant differences among the three periods（P1=0.003, P₂=0.048）.â‘¢T h17：（2.71±0.34）%、（3.39±0.73）%、（4.45±1.22）%; The ratio of Th17increased gradually, There were also significant differences among the three periods（P1=0.002, P₂=0.007）.3.The ratios of Th1,Th2,Th17cells between the infection group and the non-infectedgroup in HBV-SACLF patients were as follows:â‘ T h1：（23.59±3.91）%、（21.44±3.51）%; The difference was not statistically significant between the two groups.â‘¡Th2：（1.92±0.70）%、（1.76±0.55）%; The difference was not statistically significant betweenthe two groups.â‘¢Th17：（4.65±1.33）%、（3.92±1.27）%; There was significantly differencebetween the two groups （P=0.032）.4. The ratios of Th1,Th2,Th17cells between the survival group and the death group inHBV-SACLF patients were as follows:â‘ Th1：（20.78±3.37）%、（25.61±4.05）%; Thedifference was not statistically significant between the two groups.â‘¡T h2：（1.65±0.59）%、（1.88±0.63）%; The difference was not statistically significant between the two groups.â‘¢T h17：（3.21±1.02）%、（4.53±1.29）%; There was significantly difference between thetwo groups （P=0.029）.5. Correlation analysis of Th1,Th2,Th17and ALT of HBV-SACLF patients: Th17hadsignificant positive correlation with ALT（r=0.616， P=0.044）. Th1and Th2hadnon-significant correlation with ALT.6. The expression of IL-32, IL-10in38HBV-SACLF patients,46Pre-liver failurepatients,20CHB patients and20health adults were as follows:â‘ IL-32：（500.98±152.33）pg/ml、（486.45±129.06）pg/ml、（281.72±99.28）pg/ml、（178.16±50.54）pg/ml; The ratiosof IL-32in HBV-SACLF group were significantly higher than CHB group and controlgroup（P₂=0.021，P3=0.033）.â‘¡IL-10：（2.82±1.03）pg/ml、（3.05±1.83）pg/ml、（13.15±3.37）pg/ml、（7.62±2.17）pg/ml; The ratios of IL-10in HBV-SACLF group weresignificantly lower than CHB group and control group （P₂=0.024，P3=0.019）.7. The ratios of IL-32, IL-10in the nonage, metaphase and advanced stage of38HBV-SACLF patients were as follows:â‘ I L-32：（540.69±155.71） pg/ml、（498.43±135.56）pg/ml、（450.77±102.33）pg/ml; The ratios of IL-32decreased gradually,There were also significant differences among the three periods（P1=0.046, P₂=0.001）.â‘¡I L-10：（1.94±0.44）pg/ml、（2.83±0.97）pg/ml、（3.69±1.23）pg/ml; The ratios of IL-10 increased gradually, There were also significant differences among the three periods（P1=0.004, P₂=0.032）.Conclusion The Th1and IL-32in HBV-SACLF patients were significantly increasedand there was a gradual downward trend with the progression of the disease. Th2,Th17andIL-10were significantly higher and upward gradually with the progression of SACLF. Theratios of Th17in infection group were significantly higher than non-infected group;however, it was lower in survival group than death group and had significant positivecorrelation with ALT. In our studies, the disorders of Th1,Th2,Th17and IL-32, IL-10werekey factors in the development of HBV-SACLF. By detecting their dynamic changes inHBV-SACLF, we can judge patients’ immune status and offer theoretical basis for theclinical treatment of immune regulation.