长期抗病毒治疗的慢性乙型肝炎患者血清TIMP-1和M-CSF水平变化

摘要/Abstract

摘要： 目的探讨长期抗病毒治疗的慢性乙型肝炎(CHB)患者血清组织基质金属蛋白酶抑制物-1(TIMP-1)和巨噬细胞集落刺激因子(M-CSF)水平变化。方法纳入2017年4月—2019年2月合肥市第三人民医院收治的CHB患者148例为研究对象,连续抗病毒治疗2年。观察治疗前后血清TIMP-1和M-CSF水平变化。统计CHB患者肝硬化发生情况,并依据是否发生肝硬化分为发生组和未发生组。对比发生组和未发生组患者的临床资料。logistic多因素回归分析影响CHB患者肝硬化发生的因素。制作受试者工作特征曲线(ROC),以曲线下面积(AUC)评价血清TIMP-1、M-CSF变化对CHB患者肝硬化发生的预测效能。结果与治疗前1 d相比,治疗6个月后CHB患者血清TIMP-1和M-CSF均降低(P<0.05),ΔTIMP-1、ΔM-CSF分别为(56.6±8.3)μg/L、(62.5±9.2)ng/L。治疗2年后肝硬化发生率为24.32%。发生组丙氨酸氨基转移酶(ALT)、肝门静脉内径、肝脏弹性值(LSM)、TIMP-1,治疗6个月后TIMP-1、M-CSF均高于未发生组(P<0.05),ΔTIMP-1、ΔM-CSF则低于未发生组(P<0.05)。logistic回归分析结果显示,LSM、ΔTIMP-1及ΔM-CSF均为影响CHB患者肝硬化发生的危险因素(OR=2.732、3.040、3.330,P<0.05)。ROC分析显示,血清ΔTIMP-1、ΔM-CSF预测CHB患者肝硬化发生的最佳截断点分别为50.9 μg/L、61.4 ng/L,灵敏度分别为80.6%、72.2%;特异度分别为75.9%、80.4%,AUC分别为0.848、0.809。结论血清TIMP-1、M-CSF水平变化预测CHB患者肝硬化发生的效能较高,可作为临床评估CHB患者是否发生肝硬化的重要参考指标。

关键词: 慢性乙型肝炎, 抗病毒治疗, 组织基质金属蛋白酶抑制物-1, 巨噬细胞集落刺激因子

Abstract: Objective To investigate the changes of serum tissue matrix metalloproteinase inhibitor-1 (TIMP-1) and macrophage colony stimulating factor (M-CSF) levels in patients with chronic hepatitis B (CHB) treated with long-term antiviral therapy.Methods Between April 2017 and February 2019, 148 patients with CHB admitted to our hospital were the subjects of study and received continuous antiviral therapy for 2 years. The changes of serum TIMP-1 and M-CSF levels before and after treatment were observed. The occurrence of liver cirrhosis in CHB patients was counted and divided into an occurrence group and a non-occurring group according to whether or not liver cirrhosis occurred. The clinical data of patients in the occurrence group and the non-occurrence group were compared. Logistic multivariate regression analysis of factors affecting the occurrence of liver cirrhosis in patients with CHB. A receiver operating characteristic curve (ROC) was made, and the area under the curve (AUC) was used to evaluate the predictive power of changes in serum TIMP-1 and M-CSF on the occurrence of liver cirrhosis in patients with CHB.Results Compared with 1 day before treatment, serum TIMP-1 and M-CSF of CHB patients were reduced after 6 months after treatment (P<0.05), and ΔTIMP-1 and ΔM-CSF were (56.6± 8.3) μg/L, (62.5±9.2) ng/L. The incidence of liver cirrhosis after 2 years of treatment was 24.32%. The occurrence group alanine aminotransferase (ALT), hepatic portal vein diameter, liver elasticity value (LSM), TIMP-1, TIMP-1 after 6 months of treatment, and M-CSF after 6 months of treatment were all higher than those of the non-occurring group (P<0.05), ΔTIMP-1 and ΔM-CSF were lower than those in the non-occurring group (P<0.05). Logistic regression analysis showed that LSM, ΔTIMP-1 and ΔM-CSF were all risk factors affecting liver cirrhosis in patients with CHB (OR=2.732, 3.040, 3.330, P<0.05). ROC analysis showed that the best cut-off points of serum ΔTIMP-1 and ΔM-CSF for predicting the occurrence of liver cirrhosis in CHB patients were 50.9 μg/L and 61.4 ng/L, respectively, the sensitivity was 80.6%, 72.2%, and the specificity was 75.9%, 80.4%, and the AUC were 0.848 and 0.809, respectively.Conclusion Serum ΔTIMP-1 and ΔM-CSF have higher predictive power in predicting the occurrence of liver cirrhosis in CHB patients, and can be used as important reference indexes of whether CHB patients have liver cirrhosis. .

Key words: Chronic hepatitis B, Antiviral therapy, Tissue matrix metalloproteinase inhibitor-1, Macrophage colony stimulating factor

张磊, 黄育红, 罗凌, 汪丽萍, 方春华, 冉斌, 李应. 长期抗病毒治疗的慢性乙型肝炎患者血清TIMP-1和M-CSF水平变化[J]. 肝脏, 2022, 27(8): 863-867.

ZHANG Lei, HUANG Yu-hong, LUO Ling, WANG Li-ping, FANG Chun-hua, RAN Bin, LI Ying. Changes of serum TIMP-1 and M-CSF levels in patients with chronic hepatitis B treated with long-term antiviral therapy[J]. Chinese Hepatolgy, 2022, 27(8): 863-867.

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