| OBJECTIVES1. To observe the expression levesl of Th1/Th2cell related cytokines in patients with HBeAg positive chronic hepatitis B and its relativity to different liver function, HBVDNA loads and HBeAg levels and to explore the antivirus effect of Th1/Th2cell related cytokines in immune defense in patients with HBeAg positive chronic hepatitis B.Try to provide references for antivirus therapy.2. To observe the changes of Th1/Th2cell related cytokines after Telbivudine therapy and to explore the effect of Telbivudine therapy on immunity. Try to predict effectiveness of Telbivudine therapy.METHODS1. We collected clinical data of patients with HBeAg positive chronic hepatitis B in The Second Hospital of Shandong University and Tianjin Infectious Hospital between October2009and January2011and recorded clinical data such as blood routine examination, liver function, renal function, cards cardiac enzymes, HBVDNA loads, HBeAg levels, prothrombin activation and so on. Cases were grouped according to liver function, HBVDNA loads and HBeAg levels.20healthy volunteers were used as control group.2. All cases received600mg of Telbivudine daily for48weeks. Clinical data were recorded in12weeks,24weeks and48weeks after treatment3. Sera were collected before treatment and in12weeks,24weeks and48weeks after treatment.4. ELISA was used to test the levels of IFN-γ, TNF-α, IL-4and IL-10. We analyzed the changes of cytokines and their relations to response degree.5. SPSS17.0was used to do statistics analysis.RESULTS1. A total of58patients was enrolled. There were14cases,24cases and20cases respectively according to liver function. There were16cases,25cases and17cases respectively according to HBVDNA loads. There were16cases,24cases and18cases respectively according to HBeAg levels.2. The levels of cytokines in different liver function groups were as follows:The levels of IFN-y (pg/ml) of severe group(31.94), moderate group(25.19) and mild group(24.53)were lower than that of control group(35.65). The levels of IFN-γ of severe group were higher than of moderate group and mild group (p<0.05). There is no difference between mild group and moderate group (p>0.05). The levels of TNF-a (pg/ml) among severe group (7.58), moderate group (7.43), mild group (7.49) and control group (7.95) had no significant differences (all p>0.05). The levels of IL-4(pg/ml) of severe group(40.77) and control group(43.83) were lower than that of moderate group(46.84)and mild group(52.13)(p<0.05) and there was no difference between severe group and control group(p>0.05). There was no significant difference between mild group and moderate group (p>0.05) either. The levels of IL-10(pg/ml) of severe group (51.28) and control group (51.08) were lower than that of moderate group (56.47) and mild group (54.68)(p<0.05), and there was no significant difference between severe group and control group (p>0.05). There was no significant difference between mild group and moderate group (p>0.05).3. The levels of cytokines in groups of different HBVDNA loads had no significant differences (p>0.05all).4. The levels of cytokines in groups of different HBeAg levels have no significant differences either (p>0.05all).5. Liver function of CHB patients positively correlated with the levels of IFN-y(r=0.59p<0.05) and negatively with the levels of IL-4(r=-0.479p<0.05) and IL-10(r=-0.24p<0.05). There was no correlation between liver function and the levels of TNF-α.6. All58cases required response in varying degrees. Among them,15(25.86%) cases required complete response and43(74.14%) cases required incomplete response. Among different liver function groups there were11(55.00%) cases required complete response which were higher than1(7.10%) case of mild group and3(8.33%) cases of moderate group. There have significant differences among the three groups(x2=27.03p<0.05). Among different HBVDNA loads groups there were 10(58.82%) cases who required complete response in low HBVDNA loads group and there were only2(12.5%) cases in high HBVDNA loads group and3(12.00%) cases in moderate HBVDNA loads group who required complete response. There had significant differences among the three groups(x2=29.10p<0.05). Among different HBeAg levels, there were12(75.00%) cases who required complete response in low HBeAg level group which was higher than1(5.56%) case in high HBeAg levels and2(8.33%) cases in moderate HBeAg levels. There had significant differences among the three groups(x2=39.03p<0.05). The levels of IFN-γ (pg/ml)(z12=-4.62, z24=-4.68, z48=-5.06) of patients who required complete response increased gruduanlly while the levels of IL-4(pg/ml)(z24=-3.28, z48=-4.05) and IL-10(pg/ml)(z24=-3.31, z48=-4.12) decreased gradually. The cytokines of patients who didn’t require complete response had no significant changes.7. Among different liver function groups the levels of IFN-γ in severe group after treatment period of12weeks(z=-4.68, p<0.05) increased significantly and up to24weeks(z=-4.65, p<0.05) increased further and up to48weeks(z=-5.11, p<0.05) still sustained a high level. There were significant differences between before treatment and post treatment. But the changes of the levels of IFN-γ in moderate group and in mild group had no differences. The levels of TNF-α among the three groups had no significant differences after Telbivudine treatment. The levels of IL-4in severe group decreased after treatment period of24weeks and48weeks. While in moderate group and mild group there were no changes after treatment. The levels of IL-10had the same changes as the IL-4.8. Among different HBVDNA loads groups the levels of IFN-γ in low HBVDNA loads group after treatment increased gradually (12weeks z=-2.19,24weeks z=-2.29and48weeks z=-2.91respectively) and there were significant changes after treatment (all p<0.05). There were no significant changes in moderate HBVDNA loads group and in high HBVDNA loads group. The levels of TNF-α among the three groups had no significant changes after treatment. The levels of IL-4in low HBVDNA loads group decreased gradually (12weeks z=-2.19,24weeks z=-2.26and48weeks z=-2.33respectively) and there were significant changes after treatment. There were no significant changes in moderate HBVDNA loads groups and high HBVDNA loads group. The levels of IL-10in low HBVDNA loads group decreased gradually (12weeks z=-2.02,24weeks z=-2.15and48weeks z=-2.02respectively) and there were significant changes after treatment. There were no significant changes in high HBVDNA loads groups and moderate HBVDNA loads group.9. Among different HBeAg levels groups the levels of IFN-γ in low HBeAg levels group after treatment increased gradually(12weeks z=-2.05,24weeks z=-2.22and48weeks z=-2.26respectively) and there were significant changes after treatment(all p<0.05).There were no significant changes in moderate HBeAg levels group and in high HBeAg levels group. The levels of TNF-a among the three groups had no significant changes after treatment. The levels of IL-4in low HBeAg levels group decreased gradually (12weeks z=-2.22,24weeks z=-2.36and48weeks z=-2.22respectively) and there were significant changes after treatment. There were no significant changes in moderate HBeAg levels group and in high HBeAg levels group.The levels of IL-10in low HBeAg levels group decreased gradually (12weeks z=-2.07,24weeks z=-1.99and48weeks z=-2.22respectively) and there were significant changes after treatment(all p<0.05). There were no significant changes in high HBeAg levels groups and in moderate HBeAg levels group (all p>0.05).CONCLUSIONS1. The levels of Th1/Th2cell related cytokines in groups of different liver function in HBeAg positive CHB patients had differences. Liver function of CHB patients positively correlated with the levels of IFN-γ and negatively with the levels of IL-4and IL-10. There was on correlation between liver function and the levels of TNF-α.There was no correlation between cytokines and HBVDNA loads as well as HBeAg levels.The immunity of patients with HBeAg positive chronic hepatitis B could be reflected by the levels of Thl/Th2cell related cytokines and Th1/Th2cell related cytokines could provide reference for antivirus therapy.2. After Telbivudine therapy patients whose liver function were damaged severely, who had low HBVDNA loads and low HBeAg levels would have a good response degree. The levels of IFN-y in patients who had complete response increased gradually. The levels of IL-4and IL-10decreased gradually. The levels of TNF-α had no significant changes. Cytokines of patients who had incomplete response after treatment had no significant changes. The levels of Th1/Th2cells cytokines could be predictors of antivirus effectiveness.3. The levels of IFN-γ increased gradually while the levels of IL-4and IL-10decreased gradually and the levels of TNF-α had no significant changes after Telbivudine therapy in patients who had complete response. All cytokines had no significant changes in patients who had incomplete response. The levels of Th1/Th2cell related cytokines changes could profict antiviral theapy effectiveness. Telbivudine treatment leads to high HBeAg seroconversion which may be related to its immunoregulation. |
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