The Increased Th17 Cells In Chronic Hepatitis C Patients And Its Correlations With Antiviral Therapy

Objective:To investigate the characteristics of Th17 cells in HCV-associated chronic hepatitis and liver cirrhosis patients by observing the expression frequency of Th17 cells in peripheral blood and biopsy liver tissue in different populations and different stages of disease. To illustrate the related factors in the expression of Th17 cells and the correlations between Th17 and the Rapid Virological Response (RVR), Early Virological Response (EVR) after combinational administration of Peginterferon alfa-2a plus Ribavirin.Method:Th17 cell frequency were measured in 87 patients with chronic hepatitis C,30 patients with HCV-associated liver cirrhosis and 34 healthy cases as control group. Thl7 cell frequency and liver tissue in situ IL17 expression were compared among the different group patients. Multivariate analysis and multivariate logistic regression were performed to determine the features associated with the Th17 cell frequency. In the following clinical trial,60 patients with CHC were included in combination treatment of peginterferon alfa-2a plus ribavirin. The Th17 frequency changes were detected at different points (before treatment and at 1st week,2nd week,4th week,12th week after antivirual treatment). The correlations betwwen Th17 cell frequency and RVR, EVR were discussed primarily.Results:The Th7 cell frequency in peripheral bloou cf CHC patients were higher than HCV-LC patients(3.20%±1.54%versus 2.68%±1.69%,p=0.1530)and HC cases (3.20%±1.54%versus 2.42%±0.83%,p=0.0063). The frequency of Th17 cell in patients with CHC was correlated with elevated serum transaminases (correlation coefficient with ALT 0.6204, with AST 0.5798), hepatitis C viral load and HCV genotype (p<0.05). Intrahepatic in situ expression of IL-17 in patients with CHC was higher than that of HC. With the increase of liver tissue inflammation grade, more and more IL-17 positive cells in situ expression were founded. This result was consistent with that of peripheral blood. In the combination treatment of peg-interferon alfa-2a plus ribavirin trail, the Th17 cell frequency in patients of RVR group was higher than that of Non-RVR group (4.08%±1.08%versus 2.98%±1.37%,p=0.0105) before treatment; the Th17 cell frequency in patients of EVR group was higher than that of Non-EVR group (3.66%±1.62%versus 2.19%±0.77%,p=0.0156) before treatment. In the further analysis, the Th17 cell frequency returned to normal level gradually 1 week after combination treatment in RVR and EVR group. Nevertheless, the Th17 cell frequency began to increase gradually 1 week after combination treatment in NON-RVR and NON-EVR group. Th17 cell frequency in patients of Non-RVR and Non-EVR group were higher than that of RVR and EVR group in the 2,4,12 week after treatment.Conclusions:Our data show that there is an increase of Th17 cells in patients with chronic HCV infection compared with health control. In particular, the increased Th17 cells are correlated with the severity of liver inflammation. The CHC patients with higher Th17 frequency before combinational treatment of Peginterferon a 2a plus Ribavirin exhibits better RVR and EVR. Th17 cells can be used as an immunological predictor for virological response the in CHC patients with antivirual treatment.