| Objective:1. To observe the balance of Treg/Th17cell and related cytokines in patients with HBeAg positive chronic hepatitis B and its relativity to liver function, HBV-DNA loads, HBsAg and HBeAg levels, in order to explore the role of Treg/Th17balance in the pathogenesis of HBeAg positive chronic hepatitis B. To provide references for antivirus therapy.2. To observe the change of Treg/Th17cell and related cytokones under telbividine therapy and to explore the effect of telbivudine therapy on cell immunity. And analyze the relationship between the change of Treg/Th17and the HBeAg negative or the HBeAg level, in order to provide the immunology marker for predicting the HBeAg seroconversion.Methods:We collected27HBeAg positive Chronic Hepatitis B(CHB) patients in Tianjin Second People’s Hospital between September2012and September2013, all cases received600mg of telbivudine daily for24week. Flow cytometry was employed to count the Treg and Th17frequency in peripheral blood and the serum TGF-β1and IL-17levels were detected by ELISA at each4weeks. And collected the clinic data in different therapy time point. To compare the difference of Treg/Th17cell between CHB patients and health control, analyse the relationship of between the Treg/Th17cell and clininc data, observe the change of the Treg/Th17cell and related cytokines under telbividine therapy, and analyze the relationship of between the Treg/Th17ration and HBeAg level.Results:1. The peripheral blood Treg cell frequency, Th17cell frequency and the ratio of Treg/Th17increased significantly in CHB patients compared with healthy controls (P<0.05). And the serum TGF-β1and IL-17level were higher significantly than healthy controls in CHB patients (P<0.05).2. The peripheral blood Treg cell frequency, serum TGF-β1level, Treg/Th17ratio and TGF-β1/IL-17ratio positively correlated with the serum HBV-DNA level. Th17cell frequency and serum IL-17level positively correlated with ALT level (P<0.05); however, Treg/Th17ratio and TGF-β1/IL-17ratio negatively correlated with ALT level(P<0.05). Treg cell frequency, serum TGF-β1level and Treg/Th17ratio positively correlated the serum HBsAg level (P<0.05). Treg cell frequency, serum TGF-β1level and TGF-β1/IL-17ratio positively correlated the serum HBeAg level(P<0.05).3. The serum HBV-DNA level, ALT level, HBsAg and HBeAg level decreased significantly at the early period of telbividine therapy, the HBV-DNA negativety rate was88.9%, the ALT normolized in all patients and the level of HBsAg/HBeAg reduced significantly compared with the baseline at24weeks(P<0.05). And there were6patients happened the HBeAg negativity, two of6patients happened the HBeAg seroconversion.4. Durring the treatment of telvibudine, the peripheral blood Treg cell frequency and the serum TGF-β1level decreased significantly at8week,4weeks respectively compared with the baseline (P<0.05). The Th17cell frequencey and IL-17level reached to the maximal peak at8weeks, and were higher significantly than the baseline (P<0.05). But the level decreased from the12weeks and remained higher than those at the baseline. They showed a reverse"V"type change with the maximal peak at the8week. The Treg/Th17ratio and TGF-β1/IL-17ratio were decreased during the treatment, the ratio were less significantly than the baseline at8weeks (P<0.05), and decreased to the lowest at12weeks, and increased slightly from12week to24week.5. At24weeks, the Treg cell frequency and the Treg/Th17ratio were lower in HBeAg negative patients than in HBeAg non-negative patients,(P<0.05). Both the peripheral blood Treg cell frequency and the serum TGF-β1level showed positive correlation with HBeAg level during the telbivudine therapy.Conclusions:1. The imbalance of Treg/Th17and TGF-β1/IL-17was observed in HBeAg positive chronic hepatitis B patients. The Treg cell frequency and TGF-β1level positively correlated with the serum HBV-DNA, HBsAg level and HBeAg level, this suggested that the Treg cell was correlated with the HBV persistly infected. The Th17 cell frequency and IL-17level postitively correlated with the ALT level, this suggested that the Th17cell causeed the immunity injury. Observing the change of Treg/Th17ratio may provide references for antivirus therapy.2. The telbivudine therapy not only suppressed the HBV-DNA replication rapidly but have the immunomodulatory effect on the Treg/Th17balance. The decrease of the Treg cell frequency and TGF-β1level were contributed to break the immune tolerance, The increase of the Th17cell frequency and IL-17level were contributed to the immune injury and to clear the HBV-DNA.3. HBeAg negative patients showed the weaker immune tolerance, the less Treg cell frequency at the baseline, the more HBeAg negative. So the Treg/Th17balance may influence the HBeAg negative. Both the peripheral blood Treg cell frequency and the serum TGF-β1level showed positive correlation with HBeAg level during the telbivudine therapy. So maybe we could predict the HBeAg negative by the change of Treg cell frequency and TGF-β1level. |
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