田玉球 周宁 蒋永芳

[摘要] 目的 探討粒细胞集落刺激因子联合恩替卡韦治疗早期乙肝慢加急性肝衰竭（ACLF）效果及对患者血管紧张素Ⅱ（AngⅡ）、肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）水平的影响。 方法 选择2016年1月～2017年6月中南大学湘雅二医院感染内科治疗的84例早期乙肝ACLF患者，按照随机数字表法分为对照组（42）例和观察组（42例）。常规治疗基础上，对照组给予恩替卡韦治疗，观察组在对照组基础上联合粒细胞集落刺激因子治疗。比较两组患者临床疗效、肝功能指标及AngⅡ、TNF-α、IL-10水平。 结果 观察组患者治疗总有效率高于对照组，差异有统计学意义（P < 0.05）。治疗后，与对照组比较，观察组患者肝功能指标总胆红素水平降低，白蛋白、凝血酶原活动度水平升高，差异有统计学意义（P < 0.05）。治疗后，与对照组比较，观察组AngⅡ、TNF-α水平降低，IL-10水平升高，差异有统计学意义（P < 0.05）。 结论 粒细胞集落刺激因子联合恩替卡韦在早期乙肝ACLF患者中应用效果良好，治疗有效率高，能够有效改善肝功能，降低AngⅡ水平，并改善炎性反应，临床上值得应用。

[关键词] 粒细胞集落刺激因子；恩替卡韦；慢加急性肝衰竭；肝功能；促血管生成素Ⅱ；肿瘤坏死因子α；白细胞介素10

[中图分类号] R575.3 [文献标识码] A [文章编号] 1673-7210（2018）06（b）-0139-04

[Abstract] Objective To investigate the curative efficacy of granulocyte colony-stimulating factor in combination with entecavir in patients with hepatitis B virus related acute-on-chronic liver failure （ACLF） at early stage and its influences on levels of angiotensin Ⅱ （AngⅡ）， tumor necrosis factor α （TNF-α）， interleukin 10 （IL-10）. Methods From January 2016 to June 2017， in Department of Infedtious Diseases， Xiangya No.2 Hospital of Central South University， 84 patients with hepatitis B virus related ACLF at early stage were collected， according to random number table， they were divided into the control group and the observation group， with 42 cases in each group. Besides conventional treatments， the control group was treated with entecavir， while the observation group was treated with granulocyte colony-stimulating factor in combination with entecavir. Curative efficacy， levels of indices of liver function， AngⅡ， TNF-α and IL-10 were compared between the two groups. Results The total therapeutic efficacy ratio in the observation group was statistically higher than that in the control group， the difference was statistically significant （P < 0.05）. Compared with the control group， the observation group had lower level of total bilirubin and higher levels of albumin， prothrombin activity after treatment， the differences were statistically significant （P < 0.05）. After treatment， compared with the control group， the observation group had lower levels of AngⅡ， TNF-α and higher level of IL-10， the differences were statistically significant （P < 0.05）. Conclusion Granulocyte colony-stimulating factor in combination with Entecavir has well application effect in patients with hepatitis B virus related ACLF at early stage with a high therapeutic efficacy ratio. And it can effectively improve liver function， reduce level of AngⅡ and improve inflammatory reaction.

[Key words] Granulocyte colony-stimulating factor； Entecavir； Acute-on-chronic liver failure； Liver function； Angiotensin Ⅱ； Tumor necrosis factor α； Interleukin 10

慢加急性肝衰竭（acute-on-chronic liver failure，ACLF）是一种以严重肝脏损害为主要表现的临床症候群，具有病情严重、并发症多等特点，在我国具有较高的发病率，其中乙型肝炎病毒感染是该疾病的重要病因[1]。机制研究显示[2]，血管紧张素Ⅱ（AngⅡ）水平在肝衰竭患者中升高，且与不良预后相关。另外，ACLF患者中抗炎因子和促炎因子失衡，促进疾病进展[3]。恩替卡韦是乙型肝炎病毒常用的抗病毒药物，对早期乙肝ACLF具有治疗意义[4]。但是，早期乙肝ACLF的治疗效果不甚理想，临床上一直在寻求提高疗效的治疗方案。粒细胞集落刺激因子是长期用于治疗粒细胞缺乏等疾病的一种药物，其动员骨髓干细胞、促进肝组织修复及免疫调节等多种功能已经得到证实，逐渐在肝衰竭治疗中受到关注[5]，但有必要进一步扩大临床证据。……