血清IL-35、IL-17与恩替卡韦治疗慢性乙型肝炎患者HBeAg阴转的相关性

摘要/Abstract

摘要： 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。

关键词: 慢性乙型肝炎, 恩替卡韦, IL-35, IL-17, HBeAg

Abstract: 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 HBeAg-negative 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). Conclusion ETV 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.

Key words: Chronic hepatitis B; Entecavir; Interleukin-35; Interleukin-17; Heptitis B e antigen

张曹庚, 张志峰, 张红云, 顾海蔚, 刘红, 倪菊平, 施燕芬, 徐瑞芳. 血清IL-35、IL-17与恩替卡韦治疗慢性乙型肝炎患者HBeAg阴转的相关性[J]. 肝脏, 2018, 23(12): 1073-1077.

ZHANG Cao-geng,ZHANG Zhi-feng, ZHANG Hong-yun, GU Hai-wei, LIU Hong, NI Ju-ping, SHI Yan-fen, XU Rui-fang. Correlations between serum IL-35, IL-17 and HBeAg clearance in chronic hepatitis B patients treated with entecavir[J]. Chinese Hepatolgy, 2018, 23(12): 1073-1077.

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