The Role Of Th17and Treg Cells In HBeAg Positive CHB Patients Treated With Peg-interferon

Objective: chronic hepatitis B caused by HBV infection is our commonchronic infectious diseases, it become one of the major risk factors thatendanger public health. Immune function plays an important role in theprocess to clear the hepatitis B virus. The persistence of the virus to induceimmune response, while clearing the virus, immune response can damageliver cells. Antiviral therapy is an effective treatment for chronic hepatitis Btreated with peg-interferon. The function of newly discovered Th17andTreg cell, respectively, for the promotion and suppression of the immuneresponse. In normal circumstances, two cells should be in an immune stateof balance, but studies have shown that this balance in patients with chronichepatitis B was broken. This study was designed to explore in the processof pegylated interferon treatment of chronic hepatitis B, the changecharacteristic of T helper cells, as well as dynamic variation in the processof antiviral therapy, and analyze the role of Th17/Treg cell immune balancein HBV persistence infection.Methods: Select11cases without take the anti-virus treatment of HBeAg-positive chronic hepatitis B patients, give them pegylatedinterferon antiviral therapy according to conventional doses and methodsfor48weeks, and collection of peripheral blood of patients at baseline,treatment4,8,12,24,32,40,48weeks, the cells were stained by streamingantibody. Flow cytometry were used to detect the ratio of Th17cells, Tregcells, Th1cells, Th2cells in peripheral blood, and then, analysis the trendof the cells in the anti-viral treatment process, observe the correlationbetween them and the correlation with the HBV-DNA quantitative and ALTlevels.Results:1. The change trend of Th17, Treg, Th1, Th2cells in the peripheralblood of interferon treatment process at each time point: In the early4weeks treated by interferon, Th1cells declined rapidly, during4-24weeks,it express a slow trend of fluctuations, and become significantly higherafter24weeks. Th2cells appear a level fluctuation trend during thetreatment, have no significant change. Th17cells showed an upward trendin the first eight weeks in therapy, Treg cells is rapid increase in theprevious four weeks, after this, it appear the rapid decline trend, to theeighth week, two cells reach to the similar levels, followed by, Treg cellsdecreased slowly, and Th17was broken line fluctuations, to48weeks oftreatment, both reach to a similar level again.2. For the48weeks treatment of HBeAg dropped to1COI is divided into Group A:<1COI; Group B:>1COI. There are no significant differnceof Th1and Th2in those two groups. But in the4th week of treatment,Th1/Th2level showed a fast decline, after the state was continuing lowlevel in both two groups. No significant difference of Treg cells betweenGroup A and Group B. However, There were significant differences ofTh17and Th17/Treg between the two groups, group B showed an upwardtrend in the first eight weeks, followed by gradual decline, group A showeda gradual increase state. In addition, we found Th1/Th17, Th2/Th17in first16weeks are all showed a low level states, in the24th week of Group B itremained low, while in group A showed a significant higher level. Nosignificant differences of Th1/Treg, Th2/Treg between the two groups. Forthe48weeks treatment of HBV-DNA down to103copy/ml is divided intotwo groups, we found that there are similar changes.3. Analysis the correlation of the Th1/Th2, Th17/Treg ratios andHBV-DNA load, ALT in the process of PegIFN treatment: Aoccording toPearson correlation anlysis, Th1cells and Treg cells have the positivelycorrelated (p<0.001), Th2cells and Th17cells have the positivelycorrelated (p<0.05), Th17and Treg cells, Th1and Th2cells showed theopposite trend in the course of treatment, there is a negatively correlationbetween Th17/Treg proportion and HBV-DNA (p<0.05), but no significantcorrelation between Th1/Th2ratio and HBV-DNA, however, there is apositive correlation between Th1cells and HBV-DNA load (p <0.05). Conclusions: Treg cells in the peripheral blood of chronic hepatitis Bvirus infection have a low expression, and in the inhibition state, but Th17cells in a functionally active state, this balance disorders maybe related tothe severity of the disease in a certain extent. In the process of Interferonanti-viral treatment, Th17and Treg cells, Th1and Th2cells showed theopposite trend in the course of treatment, there is a negatively correlationbetween Th17/Treg proportion and HBV-DNA, so we speculate that theimbalance Th17/Treg played an important role in the process of hepatitisB virus persistence.