恩替卡韦治疗的乙型肝炎肝硬化患者血清TIMP-1、MMP-2和GP73水平变化

摘要/Abstract

摘要： 目的探讨恩替卡韦治疗的乙型肝炎肝硬化患者血清金属蛋白酶抑制剂-1(TIMP-1)、基质金属蛋白酶-2(MMP-2)和高尔基体蛋白73(GP73)水平变化。方法搜集2019年6月至2020年5月收治的76例乙型肝炎肝硬化患者,采用随机数字表法将其分为对照组和观察组,每组各38例。对照组采用常规治疗,观察组在对照组的基础上另给予恩替卡韦治疗。比较两组患者治疗后总胆红素(TSB)、白蛋白(Alb)、国际标准化比值(INR)、血清TIMP-1、MMP-2、GP73水平及影像学指标;对比两组临床疗效及不良反应。结果治疗3、6、12个月后,观察组TSB分别为[(30.1±5.3)μmol/L、(27.6±4.8)μmol/L、(22.4±4.2)μmol/L],Alb分别为[(28.5±3.7)g/L、(32.6±4.5)g/L、(39.4±5.2)g/L]明显高于对照组[(23.7±3.5)g/L、(29.1±4.2)g/L、(34.2±4.3)g/L](TSB:t=3.518,2.288,46.80;INR:t=4.359,4.258,4.052;P均＜0.05),INR分别为[(1.4±0.1)、(1.2±0.1)、(1.1±0.0)]均明显低于对照组[(1.5±0.1)、(1.3±0.1)、(1.2±0.1)](t=5.810,3.505,4.751;P均＜0.05)。治疗3、6、12个月后,观察组血清TIMP-1分别为[(295.4±45.7)ng/mL、(262.3±40.2)ng/mL、(234.2±32.8)ng/mL],MMP-2分别为[(726.5±66.3)ng/mL、(683.2±59.7)ng/mL、(601.4±52.6)ng/mL],GP73水平分别为[(73.1±9.5)ng/mL、(54.1±7.8)ng/mL、(35.4±6.3)ng/mL],均明显低于对照组[血清TIMP-1:(317.2±50.1)ng/mL、(281.4±42.7)ng/mL、(251.8±39.2)ng/mL,MMP-2:(759.8±69.3)ng/mL、(711.4±57.2)ng/mL、(631.8±55.2)ng/mL,GP73:(82.8±10.7)ng/mL、(62.4±8.1)ng/mL、(50.7±7.6)ng/mL](TIMP-1:t=2.164,2.008,2.123;MMP-2:t=2.140,2.103,2.458;GP73:t=4.179,4.550,9.554;P均＜0.05);治疗3、6、12个月后,观察组肝硬度数值分别为[(17.6±4.1)kPa、(14.1±3.6)kPa、(13.1±3.2)kPa]明显低于对照组[(19.8±4.3)kPa、(15.8±3.9)kPa、(14.6±3.7)kPa](t=2.283,2.091,2.142;P均＜0.05);治疗6、12个月后,观察组脾脏厚度分别为[(41.6±3.2)mm、(40.5±2.6)mm]低于对照组[(43.7±3.1)mm、(41.9±2.7)mm],(t=2.906,2.302;P均＜0.05)。结论恩替卡韦治疗乙型肝炎肝硬化可改善患者肝功能,降低肝硬度数值、脾脏厚度,调节血清TIMP-1、MMP-2和GP73水平。

关键词: 恩替卡韦, 乙型肝炎, 肝硬化, 金属蛋白酶抑制剂-1, 基质金属蛋白酶-2, 高尔基体蛋白73

Abstract: Objective To investigate the changes of serum tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-2 (MMP-2) and golgi protein 73 (GP73) levels in patients with hepatitis B cirrhosis treated with entecavir. Methods Seventy-six patients with hepatitis B cirrhosis admitted to our hospital from June 2019 to May 2020 were enrolled, and they were randomly divided into control group and study group, with 38 cases in each group. The control group was treated with routine treatment, and the observe group was added with entecavir treatment. The levels of total bilirubin (TBil), albumin (Alb), international normalized ratio (INR), serum TIMP-1, serum MMP-2, serum GP73 and imaging indexes were compared between the 2 groups. The clinical efficacy and adverse reactions of the 2 groups were compared. Results After 3, 6, 12 months of treatment, TBil of study group were (30.1±5.3) μmol/L, (27.6±4.8) μmol/L, (22.4±4.2) μmol/L, respectively. The Alb level of study group at 3, 6, 12 months after treatment were (28.5±3.7) g/L, (32.6±4.5) g/L, (39.4±5.2) g/L, which were significantly higher than those of control group [(23.7±3.5) g/L, (29.1±4.2) g/L, (34.2±4.3) g/L] (TBil: t=3.518, 2.288, 46.80; INR: t=4.359, 4.258, 4.052; all P<0.05). The INR of study group at 3, 6, 12 months after treatment were (1.4±0.1), (1.2±0.1), (1.1±0.0), which were significantly lower than those of control group [(1.5±0.1), (1.3±0.1), (1.2±0.1)] (t=5.810, 3.505, 4.751, all P<0.05). After 3, 6, 12 months of treatment, the serum TIMP-1 of study group were (295.4±45.7) ng/mL, (262.3±40.2) ng/mL, (234.2±32.8) ng/mL, the serum MMP-2 level of study group were (726.5±66.3) ng/mL, (683.2±59.7) ng/mL, (601.4±52.6) ng/mL, the serum GP73 level of study group were (73.1±9.5) ng/mL, (54.1±7.8) ng/mL, (35.4±6.3) ng/mL, which were significantly lower than those in control group [TIMP-1: (317.2±50.1) ng/mL, (281.4±42.7) ng/mL, (251.8±39.2) ng/mL, MMP-2: (759.8±69.3) ng/mL, (711.4±57.2) ng/mL, (631.8±55.2) ng/mL, GP73: (82.8±10.7) ng/mL, (62.4±8.1) ng/mL, (50.7±7.6) ng/mL](TIMP-1: t=2.164, 2.008, 2.123, MMP-2: t=2.140, 2.103, 2.458, GP73: t=4.179, 4.550, 9.554, all P<0.05). After 3, 6, 12 months of treatment, the liver hardness of study group (17.6±4.1) kPa, (14.1±3.6) kPa, (13.1±3.2) kPa was significantly lower than that of the control group [(19.8±4.3) kPa, (15.8±3.9) kPa, (14.6±3.7) kPa] (t=2.283, 2.091, 2.142, all P<0.05). After 6, 12 months later treatment, the spleen thickness of the study group [(41.6±3.2) mm, (40.5±2.6) mm] was lower than that of control group [(43.7±3.1) mm, (41.9±2.7) mm] (t=2.906, 2.302, all P<0.05). Conclusion Entecavir can improve the liver function, reduce the liver hardness value, spleen thickness and regulate the serum TIMP-1, MMP-2, GP73 levels in patients with hepatitis B cirrhosis.

Key words: Entecavir, Hepatitis B, Cirrhosis, Tissue inhibitor of metalloproteinase-1, Matrix metalloproteinase-2, Golgi protein 73

刘文艳, 马世河, 黄贵, 陈冲, 郑义彬. 恩替卡韦治疗的乙型肝炎肝硬化患者血清TIMP-1、MMP-2和GP73水平变化[J]. 肝脏, 2022, 27(5): 536-539.

LIU Wen-yan, MA Shi-he, HUANG Gui, CHEN Chong, ZHENG Yi-bin. Changes of serum TIMP-1, MMP-2 and GP73 levels in patients with hepatitis B cirrhosis treated with entecavir[J]. Chinese Hepatolgy, 2022, 27(5): 536-539.

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