目的 观察恩替卡韦 (ETV) 治疗慢性乙型肝炎 (CHB) 患者血清IL-35、IL-17表达水平的动态变化, 探讨其与HBeAg阴转的相关性.方法 纳入HBeAg阳性CHB患者48例, 给予ETV抗病毒治疗.分别于基线、治疗第12、24、36、48周检测HBeAg滴度、HBV DNA载量、ALT、血清IL-35、IL-17水平.根据48周时HBeAg状态将患者分为HBeAg阴转组和HBeAg未阴转组, 进行对比分析.结果 ETV治疗48周时, 48例患者中41例 (85.42％) ALT复常, 46例 (95.83％) 获得完全病毒学应答, 2例 (4.17％) 获得部分病毒学应答, 无患者发生病毒学突破, 11例 (22.92％) 患者获得HBeAg阴转.HBeAg未阴转组与HBeAg阴转组基线血清IL-35、IL-17表达水平和IL-35/IL-17比值均高于健康对照组 (均P＜0.05), 但两组间差异无统计学意义 (均P＞0.05);治疗中, 两组患者的血清IL-35水平较基线均出现不同程度的下降 (均P＜0.05), 至疗程第48周时, 两组间的差异有统计学意义[ (65.35±23.10) pg/mL对 (45.64±19.77) pg/mL, P=0.0421];两组血清IL-17水平较基线无显著改变 (均P＞0.05), 两组间差异均无统计学意义 (均P＞0.05);两组IL-35/IL-17比值和HBeAg滴度较基线也均出现不同程度的下降 (均P＜0.05), 两组间差异有统计学意义 (均P＜0.05) .结论 ETV持续抗病毒治疗能够降低CHB患者血清IL-35水平.抗病毒治疗中血清IL-35表达水平和IL-35/IL-17比值的动态变化或许能预测HBeAg阴转.%Objective To study the dynamic changes of serum levels of interleukin-35 (IL-35) and interleukin-17 (IL-17) during the 48-week entecavir (ETV) treatment and to investigate their relationship with hepatitis B e antigen (HBeAg) clearance.Methods A total of 48 HBeAg-positive chronic hepatitis B (CHB) patients receiving antiviral treatment of ETV were followed up.Laboratory indicators including HBeAg titer, hepatitis B virus (HBV) DNA load, alanine aminotransferase (ALT), serum IL-35, IL-17 and the ratio of IL-35/IL-17 were detected at baseline, week 12, week 24, week 36 and week 48, respectively.According to the HBeAg status at week 48, the patients were divided into HBeAgnegative and HBeAg-positive group for comparative analysis.Results At week 48, 41 out of 48 (85.42％) patients achieved ALT normalization, 46 (95.83％) patients achieved complete virological response, and 2 (4.17％) patients achieved partial virological response.No patient had a virological breakthrough.A total of 11 (22.92％) patients achieved HBeAg clearance.At baseline, serum levels of IL-35, IL-17 and IL-35/IL-17 ratio in HBeAg-negative and HBeAg-positive groups were higher than those of healthy controls (P＜0.05).However, there was no significant difference between these 2 groups (P＞0.05).During treatment, serum IL-35 level in 2 groups significantly decreased (P＜0.05), and was significantly different between 2 groups at week 48 (P=0.0421).Compared with that at baseline, serum IL-17 level showed no significant changes in 2 groups (both P＞0.05), and no significant differences between 2 groups during treatment (P＞0.05).Compared with those at baseline, the IL-35/IL-17 ratios and HBeAg titers of 2 groups showed different degrees of decline (P＜0.05), with statistically significant differences between 2 groups (P＜0.05).ConclusionETV antiviral therapy can reduce the serum IL-35 level of CHB patients.The dynamic changes of serum levels of IL-35, IL-17 and IL-35/IL-17 ratio may predict HBeAg clearance during antiviral treatment.
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