血清可溶性 ST2 在停止慢性乙型肝炎长期核苷（酸）类似物治疗后的临床复发中的高表达。
Elevated expression of serum soluble ST2 in clinical relapse after stopping long-term Nucleos(t)ide analogue therapy for chronic hepatitis B.
机构信息
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
出版信息
BMC Infect Dis. 2019 Jul 19;19(1):640. doi: 10.1186/s12879-019-4261-3.
BACKGROUND
The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown.
METHODS
A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups.
RESULTS
Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy.
CONCLUSIONS
In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment.
TRIAL REGISTRATION
The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970 . Registration date: December 15, 2017.
背景
慢性乙型肝炎（CHB）患者长期核苷（酸）类似物（NA）治疗停药后常发生病毒学或临床复发。可溶性生长刺激表达基因 2（sST2）是 Toll 样受体/白细胞介素-1 受体家族的成员之一，参与多种炎症过程和免疫反应。然而，NA 治疗停药后 CHB 患者血清 sST2 的表达和功能尚不清楚。
方法
前瞻性随访 91 例按国际指南停药的非肝硬化亚洲 CHB 患者 240 周。所有患者根据 HBV DNA 和 ALT 水平分为临床复发组和非临床复发组（包括持续病毒学应答和仅病毒学复发）。采用 ELISA 法检测所有参与者的血清 sST2 水平，并比较两组间的差异。
结果
26 例患者发生临床复发，57 例患者发生病毒学复发。我们发现，NA 治疗停药后 CHB 患者 sST2 表达与 HBsAg、ALT、HBV DNA 和抗-HBc 水平呈正相关。临床复发患者血清 sST2 水平呈上升趋势，大多数患者在临床复发时出现 sST2 水平峰值。此外，临床复发组在停药后 12 周、24 周和 48 周的 sST2 水平相对较高。然而，治疗结束时 sST2 水平并不是预测长期 NA 治疗停药后临床复发的有效生物标志物。
结论
综上所述，我们发现临床复发患者 sST2 增加可能与 NA 治疗停药后炎症相关免疫反应有关。
试验注册
该试验在中国临床试验注册中心进行了回顾性注册，注册号为 ChiCTR-OOC-17013970。注册日期为 2017 年 12 月 15 日。
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