恩替卡韦联合复方甘草酸苷治疗乙型肝炎肝硬化患者疗效及对肠道菌群的影响*

doi:10.3969/j.issn.1672-5069.2021.05.009

摘要/Abstract

摘要： 目的观察恩替卡韦联合复方甘草酸苷治疗乙型肝炎肝硬化患者的疗效及对肠道菌群的影响。方法 2013年1月～2020年12月我院诊治的乙型肝炎肝硬化患者73例,采用随机数字表法将其分为对照组40例和观察组33例,分别给予恩替卡韦或恩替卡韦联合复方甘草酸苷治疗48周。采用ELISA法检测血清肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)和IL-10水平,使用法国生物梅里埃公司的ATB半自动微生物鉴定系统进行细菌鉴定,使用美国GE公司 LOGIQ E9或PHILIPS EPIQ7型彩色多普勒超声诊断仪检测门静脉内径(DPV)、脾静脉内径(DSV)和脾脏厚度(SPT)。结果在治疗48周末,观察组血清丙氨酸氨基转移酶(ALT)水平为(43.7±7.6)U/L,显著低于对照组【55.9±6.5)U/L,P<0.05】,而血清白蛋白、总胆红素和凝血酶原时间分别为(35.3±4.5)g/L、(15.2±3.6)μmol/L和(13.3±0.8)s,与对照组【分别为(34.5±4.2)g/L、17.6±2.9)μmol/L和(13.9±0.7)s】比,差异无显著意义(P>0.05);观察组血清HBV DNA水平为(1.3±0.3)lg copies/ml,与对照组的(1.4±0.4)lg copies/ml比,无显著性差异(P>0.05);观察组粪便拟杆菌和双歧杆菌数分别为(7.9±0.8)lg GFU/g和(9.3±1.5)lg GFU/g,显著高于对照组【分别为(5.5±0.6)lg GFU/g和(7.6±1.0)lg GFU/g,P<0.05】,而大肠杆菌、肠球菌和乳酸杆菌数量分别为(7.3±0.9)lg GFU/g、(7.0±1.2)lg GFU/g和(9.8±0.6)lg GFU/g,与对照组【分别为(7.9±0.7)lg GFU/g、(7.3±1.3)lg GFU/g和(9.5±0.5)lg GFU/g】比,差异无显著意义(P>0.05);观察组血清TNF-α和IL-6水平分别为(39.6±6.5)ng/L和(33.5±5.9)ng/L,显著低于对照组【分别为(48.7±7.6)ng/L和(40.6±4.3)ng/L,P<0.05】,而两组血清IL-10水平无显著性差异【(20.3±4.1)ng/L对(23.7±4.2)ng/L,P>0.05】;观察组DPV、DSV和SPT分别为(12.9±0.9)mm、(9.2±1.3)mm和(42.5±5.1)mm,与对照组【分别为(13.1±1.0)mm、(9.7±1.4)mm和(43.8±4.9)mm】比,差异无显著性意义(P>0.05)。结论应用恩替卡韦联合复方甘草酸苷治疗乙型肝炎肝硬化患者能帮助改善肝功能,或可促进肠道菌群的恢复,值得进一步观察。

关键词: 肝硬化, 恩替卡韦, 复方甘草酸苷, 肠道菌群, 治疗

Abstract: Objective The aim of this study was to investigate the clinical predicting value of serum ascites albumin gradient (SAAG) on esophageal variceal bleeding (EVB) risk in patients with decompensated hepatitis B cirrhosis. Methods 84 patients with decompensated hepatitis B cirrhosis were admitted to our hospital between April 2017 and October 2019, and the SAAG and modified SAAG werecalculated. The Logistic multivariate analysis was used to analyze the independent impacting factors on EVB in patients with decompensatedhepatitis B cirrhosis. The receiver operating characteristic curve (ROC) was drawn and the area under the ROC (AUROC) was calculated to predict the EVB risk. Results 18 out of our series had, and 66 patients had not EVB during six-month followed-up period; the percentage of male cases older than 65 yr in patients with EBV was 72.2%,greatly older than in patients without EBV (43.9%,P<0.05); serum albumin level in patients with EVB was (35.8±2.7)g/L, significantly lower than , blood platelet count was (52.3±10.7)×10⁹/L, significantly lower than , the APTT was (45.8±5.9)s, significantly longer than ,the SAAG was (18.7±5.1), significantly higher than , and the modified SAAG was (9.2±2.4), significantly higher than in patients without EVB; the spleen thickness was (5.2±1.3)cm, significantly higher than , and the portal vein blood flow velocity was (15.2±2.9) cm/s, significantly slower than in patients without EVB; the multivariate Logistic analysis showed that serum albumin level (OR=0.435, 95%CI=0.287-0.659), ascites albumin level(OR=1.845, 95%CI=1.063-3.202), the APTT(OR=1.469,95%CI=1.272-1.697), the MELD score (OR=3.285, 95%CI=1.697-6.359) and the modified SAAG(OR=2.917, 95%CI=1.337-6.364) were the independent impacting factors for EVB in patients with decompensated hepatitis B cirrhosis(P<0.05); the AUCs of modified SAAG and MELD score for predicting EVB were 0.827 and 0.791, respectively, and theirsensitivities were 0.889 and 0.787, and the specificities were 0.636 and 0.612, respectively. Conclusion The application of SAAG is helpful to predict the risk of EVB in patients with decompensated hepatitis B cirrhosis, and worth further clinical investigation.

Key words: Liver cirrhosis, Entecavir, Glycyrrhizin, Intestinal flora, Therapy

季旻游, 李超, 赵兴忠, 武煦峰. 恩替卡韦联合复方甘草酸苷治疗乙型肝炎肝硬化患者疗效及对肠道菌群的影响^*[J]. 实用肝脏病杂志, 2021, 24(5): 641-644.

Ji Minyou, Li Chao, Zhao Xingzhong, et al. Intestinal flora changes in patients with hepatitis B-induced liver cirrhosis after entecavir and glycyrrhizin combination treatment[J]. Journal of Practical Hepatology, 2021, 24(5): 641-644.

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恩替卡韦联合复方甘草酸苷治疗乙型肝炎肝硬化患者疗效及对肠道菌群的影响^*

Intestinal flora changes in patients with hepatitis B-induced liver cirrhosis after entecavir and glycyrrhizin combination treatment

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