HBsAg致敏自体树突状细胞治疗乙肝病毒相关性慢加急性肝衰竭患者的临床效果

The clinical effects of HBsAg sensitized autologous dendritic cells in patients with HBV-related acute-on-chronic liver failure

目的观察乙型肝炎(乙肝)表面抗原(HbsAg)致敏自体树突状细胞(抗HBV-DCs)治疗乙肝病毒相关性慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)患者临床效应及对肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素-4(IL-4)水平的影响。方法选择住院治疗的64例ACLF患者为研究对象,抗HBV-DCs联合恩替卡韦(entecavir,ETV)治疗者为联合治疗组,ETV单独治疗者为单独治疗组,健康志愿者为对照组。观察治疗前后治疗组在外周血树突状细胞数量、频率、T淋巴细胞亚群及TNF-α、IFN-γ、IL-4水平的变化。结果两治疗组患者治疗前树突状细胞数量及频率较对照组水平低(P<0.05);联合治疗组与单独治疗组患者在治疗前树突状细胞数量及频率比较差异无统计学意义(P>0.05)。治疗后联合治疗组较单独治疗组上调明显(P<0.05);两治疗组在治疗前TNF-α、IFN-γ水平较对照组高,IL-4水平较对照组低,差异有统计学意义(P<0.05)。联合治疗组与单独治疗组在治疗前TNF-α、IFN-γ、IL-4水平间差异无统计学意义(P>0.05),治疗后联合治疗组TNF-α、IFN-γ水平下调较单独治疗组明显,联合治疗组IL-4水平上调水平较单独治疗组显著(P<0.05)。两治疗组治疗后TNF-α、IFN-γ水平下降明显,IL-4水平逐渐升高,治疗24周后复常,较治疗前比较差异有统计学意义(P<0.05)。治疗前两治疗组外周血CD3^+T淋巴细胞、CD4^+T淋巴细胞水平低于对照组,CD^8+T淋巴细胞水平高于对照组(P<0.05)。治疗前联合治疗组与单独治疗组间CD3^+T淋巴细胞、CD4^+T淋巴细胞、CD8^+T淋巴细胞水平差异无统计学意义(P>0.05)。治疗后联合治疗组CD3^+T淋巴细胞、CD4^+T淋巴细胞水平较单独治疗组上调明显(P<0.05)。ACLF患者治疗前外周血树突状细胞数量与CD3^+T淋巴细胞、CD4^+T淋巴细胞水平呈正相关(P<0.05),与CD8^+T淋巴细胞水平呈负相关(P>0.05)。结论抗HBV-DCs对调节树突状细胞数量及频率提升、激活T淋巴细胞、调节机体免疫失衡具有一定作用,可能成为HBV相关性肝病治疗的一种新路径。

Objective To observe the clinical effects of HBsAg sensitized autologous dendritic cells(anti-HBV-DCs)in patients with HBV-related acute-on-chronic liver failure(ACLF)and to observe the influence on TNF-α,IFN-γ and IL-4.Methods A total of 64 hospitalized patients with HBV-related ACLF were enrolled.The effects of anti-HBV-DCs combined with entecavir(ETV)and ETV alone on the number and frequency of peripheral blood dendritic cells,T lymphocyte subsets and TNF-α,IFN-γand IL-4 levels were compared.Results The number and frequency of dendritic cells in the treatment group before treatment were significantly lower than those in the control group(P<0.05).There was no significant difference in the number and frequency of dendritic cells between the two treatment groups(P>0.05).The number and frequency of peripheral blood dendritic cells in the treatment group were significantly higher than those before treatment(P<0.05).The number and frequency of peripheral blood dendritic cells in the combined treatment group were significantly higher than those in the treatment group(P<0.05).The levels of TNF-α and IFN-γin the treatment group were significantly higher than those in the control group,and the level of IL-4 was significantly lower than that in the control group(P<0.05).There was no significant difference in the levels of TNF-α,IFN-γ and IL-4 before treatment(P>0.05).The levels of TNF-α and IFN-γin the combined treatment group were significantly lower than those in the treatment group.The level of IL-4 in the combination group was significantly higher than that in the treatment group(P<0.05).The levels of TNF-α and IFN-γsignificantly decreased after treatment in the two treatment groups,and the level of IL-4 gradually increased.After treatment for 24 weeks,the difference was statistically significant(P<0.05).The levels of CD3^+T and CD4^+T in peripheral blood of the control group were significantly higher than those in the pretreatment group,and CD8^+T was significantly lower than the level of the treatment group(P<0.05).After treatment,the levels of CD3^+T and CD4^+T were significantly increased,and the level of CD8+T was significantly decreased(P<0.05).The levels of CD3^+T and CD4^+T in the combined treatment group were significantly higher than those in the treatment group after treatment(P<0.05).The number of peripheral blood dendritic cells in patients with ACLF was positively correlated with CD3^+T and CD4^+T levels(P<0.05),and negatively correlated with CD8^+T levels(P>0.05).Conclusion Anti-HBV-DCs plays an important role in regulating the number and frequency of dendritic cells,activating T lymphocytes,and regulating immune imbalance.It may become a new path for the treatment of HBV-related liver disease.