| ObjectiveTo investigate the changes of serum IFN-gamma,IL-4 and IL-21 levels in patients with chronic hepatitis B virus carrier(AsC)treated with entecavir and their clinical significance.Methods94 subjects including 41 AsC,32 chronic hepatitis B(CHB)and 21 healthy persons(NC)were enrolled.NC group did not receive treatment but only followed up.Both AsC group and CHB group received entecavir for 24 weeks.Peripheral blood samples were collected every 12 weeks before and after treatment.The levels of interferon-gamma(IFN-γ),interleukin(IL)-4 and interleukin(IL)-21 were detected by enzyme-linked immunoassay(ELISA).Results1.HBV-DNA(log10)levels: the levels in AsC and CHB groups were 7.80±1.27 、7.22±1.67 at baseline,4.62±1.49 、4.03±0.76 at 12 weeks of treatment,and 2.86±1.01 and 2.61±0.96 at 24 weeks of treatment.There was no significant difference between the transverse groups at 3 time points(P<0.05).Longitudinal analysis showed that the levels at 12 weeks and 24 weeks of treatment were significantly lower than those at baseline in AsC and CHB groups(P < 0.05).2.IFN-γ(pg/mL)level: the levels in NC group、AsC group and CHB group were 217.35± 11.94 、 253.64±59.16 、 299.94±47.21 at baseline.There was significant difference between the transverse groups(P < 0.05).The levels in AsC and CHB were 279.51±48.30、336.59±75.60 at 12 weeks,the levels of AsC and CHB groups were 325.05± 87.01、395.21±76.00 at 24 weeks.There was significant difference between the two groups at two time points(P < 0.05).Longitudinal analysis showed that the levels at 12 weeks and 24 weeks of treatment were significantly higher than those at baseline in AsC and CHB groups(P < 0.05).3.IL-4(pg/mL)level: the levels in NC group,AsC group and CHB group were 19.61± 2.55、50.39±15.49 、39.25±12.58 at baseline.There was significant difference between transverse groups(P < 0.05).At 12 weeks,the levels in AsC and CHB groups were 44.20±9.68 、34.31±9.97.At 24 weeks,the levels in AsC and CHB groups were 39.51± 11.20、25.76±3.22.There was significant difference between the two groups at two time points(P < 0.05).Longitudinal analysis showed that the levels at 12 weeks and 24 weeks of treatment were significantly lower than those at baseline in AsC and CHB groups(P < 0.05).4.IFN-γ/IL-4 ratio: the levels in NC group,AsC group and CHBgroup were 11.22±1.65 、 6.39±2.79 、 8.74±3.70 at baseline.There was significant difference between transverse groups(P < 0.05).At 12 weeks,the levels in AsC and CHB groups were 7.22±2.58、10.73±4.37.At 24 weeks,the levels of AsC and CHB were 10.14±5.23,15.70±5.01.There was significant difference in the ratio of two time points between the two groups(P < 0.05).Longitudinal analysis showed that the levels at 12 weeks and 24 weeks of treatment were significantly higher than those at baseline in AsC and CHB groups(P < 0.05).5.IL-21(pg/mL)level: the levels in NC group,AsC group and CHB group were 356.40±91.74,351.05±85.80,484.27±102.74 at baseline.There was significant difference between the transverse groups(P < 0.05).At 12 weeks,the levels in AsC and CHB groups were 307.05±109.39,328.59±109.39.At 24 weeks,the levels in AsC and CHB groups were456.17±140.73、305.60±40.39.The expression of IL-21 in the two groups was irregular at 12 and 24 weeks after treatment.However,two HBeAg negative patients were found to have elevated serum IL-21 at 12 weeks after treatment.6.The correlation analysis showed that HBV-DNA was negatively correlated with IFN-γ(r=-0.54,P=0.000;r=-0.48,P=0.002;r=-0.46,P=0.002)and IFN-γ/IL-4 、 r=-0.496,r=-0.362,r=-0.589)in AsC group,while HBV-DNA was negatively correlated with IFN-γ(r=-0.39,P=0.029;r=-0.66,P=0.000;r=-0.53,P=0.002)and IFN-γ/IL-4(r=-0.50,P=0.004;r=-0.59,P=0.000;r=-0.37,P=0.037)in CHB group.Il-4and IL-21 were not correlated with each index in AsC and CHB groups at all time points(P > 0.05).Conclusion1.In the course of antiviral therapy for AsC patients,a higher response rate to hepatitis B virus was obtained,and there was no significant difference between AsC patients and CHB patients.2.During the course of antiviral therapy for patients with CHB,the level of serum IFN-γ gradually increased,and the level of IFN-γ was negatively correlated with the level of HBV-DNA,suggesting that the increased level of IFN-γ may be positively correlated with the inhibition or even elimination of HBV.3.During the course of AsC patients treatment,the serum IFN-γ/IL-4ratio gradually increased,and the level of IFN-γwas negatively correlated with the level of HBV-DNA,suggesting that the increase of IFN-γ,the enhancement of Th1 type reaction,the decrease of IL-4 level and the decrease of Th2 type reaction may be positively correlated with HBV suppression or even elimination.4.During antiviral therapy for chronic hepatitis B virus carriers,the increase of serum IL-21 level may be related to the negative transformation of HBeAg and its serological transformation. |
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