[1]First Affiliated Hospital, Kunming Medical University, Kunming, China.
Background: To explore the impact of longtime antiviral therapy with entecavir on the Peripheral Th17/Treg Cytokines and specific transcription factor (RORγt, Foxp3) in patients with chronic hepatitis B. Methods: Sixty-one patients with chronic hepatitis B, who received entecavir therapy for 48 weeks, were enrolled the study. 20 normal individuals were as control group. Serum HBVDNA load was measured by Real-Time-PCR, and the HBV markers were detected with ELISA during 48 weeks of the treatment. Serum levels of IL-17, TGF-β, IL-10 and IL-23 were measured using an enzyme-linked immunosorbent assay (ELISA). RT-qPCR method was applied to determine the expressions of RORγt and Foxp3 mRNA of peripheral blood. Result: Of the 61 patients, all HBeAg positive and with detectable HBVDNA, the majority (82.0%) had serum levels of HBVDNA over 10s(7) copies per milliliter. Chronic hepatitis B patients had significantly increased serum levels of IL-17, TGF-β, IL-10 and IL-23 compared with normal individuals (all p less than 0.001). At baseline, 12 weeks, 24 weeks and 48 weeks after treatment were significantly different in the levels of ALT, AST, TBIL, HBVDNA (all p less than 0.05). HBV viral load dropped sharply during the first two weeks. Along with the extension of treatment time, the clinical indexes gradually reduced. The rates of HBVDNA undetectable in 12 weeks, 24 weeks and 48 weeks after treatment were accounted for 31.1% (19/61), 45.9% (28/61) and 78.7% (48/61), respectively. The rates of HBeAg clearance were accounted for 14.8% (9/61), 19.7% (12/61) and 31.1% (19/61), respectively. The rates of HBeAg seroconversion were accounted for 3.3% (2/61), 4.9% (3/61) and 19.7% (12/61), respectively. Compared with pre-therapy level, a significant decrease in serum levels of IL-17, TGF-β, IL-10, IL-23 and RORγt and Foxp3 expression were found from week 48 (all p less than 0.001). Conclusion: Antiviral therapy with entecavir can improve liver function, inhibit virus replication and lower the levels of the cytokines of Th17 and Treg, and control the progress of liver disease.