核苷（酸）类药物应答不佳的慢性乙型肝炎患者优化治疗过程中血清IL-21的动态变化及意义

目的通过检测核苷（酸）类似物治疗应答不佳慢性乙型肝炎患者在优化治疗过程中血清IL-21表达水平,探讨血清IL-21水平的动态变化与患者对抗病毒应答的相关性。 方法检测25例核苷（酸）类似物治疗应答不佳的慢性乙型肝炎患者在接受优化的核苷（酸）类似物抗病毒治疗基线、12周、24周、36周、52周、64周、76周、88周和104周的血清并检测IL-21水平、HBV DNA定量、HBsAg、HBsAb、HBeAg、HBeAb和肝功能等相关指标,分析这些指标的动态变化及其之间的相关性;另选取15例HBV携带者、15例健康志愿者做对照。 结果核苷（酸）类似物治疗应答不佳的慢性乙型肝炎患者优化治疗基线血清IL-21水平与无症状携带者血清IL-21水平差异无统计学意义,但均显著高于健康对照组（P = 0.000、0.003）;核苷（酸）类似物应答不佳的慢性乙型肝炎患者在优化治疗过程中血清HBV DNA、HBsAg、HBeAg、HBeAb均呈下降趋势,且HBV DNA水平及HBsAg浓度于治疗12周内下降速度最快,HBsAg浓度降低速度随治疗时间延长逐渐减慢。基线IL-21水平与优化治疗12～24周时的病毒量变化对数值存在中等强度的负相关性（r =-0.55、P = 0.015）,36周时IL-21水平与36～52周病毒量变化存在中等强度的负相关性（r =-0.62、P = 0.001）。核苷（酸）类药物优化治疗过程中患者血清IL-21浓度呈现先升高后下降的趋势,峰值浓度在36周,为66.41 pg/ml,显著高于基线IL-21浓度（P = 0.001）,治疗至88周及104周时患者血清IL-21水平恢复到基线状态。 结论乙型肝炎病毒感染的患者血清IL-21浓度升高,优化核苷（酸）类抗病毒治疗后,慢性乙型肝炎患者血清IL-21水平呈现一过性升高,峰值与HBV DNA的抑制及HBsAg、HBeAg等变化有一定的相关性。

The dynamic changes and signification of IL-21 in the optimally treated chronic hepatitis B patients with poor response to nucleos(t)ide analogue drugs

ObjectiveTo investigate of the levels of serum interleukin-21 (IL-21) in the optimally treated chronic hepatitis B (CHB) patients with poor response to nucleos(t)ide analogue drugs to investigate the relationship between the the serum IL-21 levels, the dynamic changes and patients’ viral response to antiviral therapy. MethodsThe serum of a total of 25 CHB patients with a poor response to nucleos(t)ide analogue antiviral therapy was detached before and after optimally treated for 12, 24, 36, 52, 64, 76, 88 and 104 weeks, and the levels of IL-21, HBsAg, HBsAb, HBeAg, HBeAb, HBV DNA load and the liver function were dedected, respectively. And then the dynamic changes of these indicators and the correlation were analyzed. Fifteen cases of hepatitis B virus carriers and 15 cases of healthy volunteers were selected as controls. ResultsThere was no significant differences between the levels of the baseline IL-21 of the chronic hepatitis B patients poorly respond to nucleos(t)ide analogue antiviral therapy and the hepatitis B virus carriers, but they all significantly higher than the level of serum IL-21 concentration of the healthy people (P < 0.05). During the optimal therapy of the chronic hepatitis B patients poorly respond to nucleos(t)ide analogue antiviral therapy, the level of the serum HBV DNA, HBsAg, HBeAg and HBeAb all declined, and a rapid decline of HBV DNA during the first 12 weeks of treatment was observed, and the pace of the reduction of HBsAg slowed down with time. There was a moderate negative correlation between the IL-21 concentration of baseline and the logarithmic change of HBV load from 12 weeks to 24 weeks after treatment (r =-0.55, P < 0.05). A moderate negative correlation between the IL-21 concentration at week 36 and the decline of HBV load from week 36 to week 52 was also obversed (r =-0.62, P < 0.01). And the levels of IL-21 of the patients with CHB during treatment with nucleos(t)ide analogues increased at first and then declined and the peak concentration was 66.41 pg/ml, which came around at week 36 and was significantly higher than the baseline (P < 0.05), but at the 88th week and 104th week, the IL-21 declined to the levels that showed no significant differences compared with the baseline. ConclusionsThe levels of serum IL-21 increased in the patients with HBV infection, and after the optimal antiviral treatment with nucleos(t)ide analogue drugs, the levels of serum IL-21 of patients with CHB increased transiently, and some relevance were observed between the supression of HBV DNA, as well as the changes of the HBsAg, HBeAg and the peek concentration of the serum IL-21 of patients with CHB.