摘要
目的评估双环醇片治疗抗结核药物所致肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)的疗效,构建预测疗效的模型。方法收集2022年2—12月全国155家医院符合纳入排除标准的ATB-DILI患者,给予双环醇治疗,随访观察1、2、3、4周的肝功能指标。主要分析终点为治疗后各周丙氨酸转氨酶(alanine transaminase,ALT)复常率。采用LASSO回归筛选研究变量,根据筛选的特征因素建立logistic回归模型,构建Nomogram模型预测疗效。结果共2983例患者纳入研究,其中男性1782例,女性1201例,平均(48.8±16.6)岁。肝细胞损伤型占64.06%(1911/2983),胆汁淤积型6.57%(196/2983),混合型29.37%(876/2983)。DILI严重程度1级、2级、3级和4级分别占63.66%(1899/2983)、25.01%(746/2983)、8.88%(265/2983)和2.45%(73/2983)。治疗1、2、3、4周后,ALT复常率为65.04%、83.47%、94.90%和98.22%。不同严重程度DILI在基线期ALT和天冬氨酸转氨酶(aspartate transaminase,AST)差异有统计学意义(P<0.001),但从治疗1周起差异无统计学意义(P>0.05)。3倍ULN≤ALT<5倍ULN和ALT≥5倍ULN的患者,治疗1和2周两组ALT复常率差异具有统计学意义(χ^(2)=97.9,31.4;P<0.001)。采用LASSO回归筛选特征变量,经多因素logistic回归分析,低剂量双环醇(25 mg/次)、胆汁淤积型肝损伤、基线ALT≥5倍ULN、高血压病史、腹胀和牙龈出血是治疗1周ALT复常的影响因素。据此构建Nomogram疗效预测模型,AUC为0.656,95%CI为0.631~0.682。结论双环醇片对轻、中度ATB-DILI患者有良好的疗效,Nomogram模型对于预测短期ALT复常率有一定参考价值。
Objective To evaluate the influencing factors of bicyclol tablets in the treatment of anti-tuberculosis drug-induced liver injury(ATB-DILI),and to establish a predictive model of Nomogram for drug efficacy.Methods ATB-DILI patients who met the inclusion and exclusion criteria in 155 hospitals in China from February 2022 to December 2022 were recruited.Bicyclol treatment was given,and liver function indicators were followed up and observed for 1,2,3,4 weeks.The primary end point of the analysis was the normalization rate of ALT in each week after treatment.LASSO regression was used to screen research variables.According to the characteristic factors,the logistic regression model was established.Nomogram model was established to predict the therapeutic effect.Results A total of 2983 patients were enrolled in the study,including 1782 males and 1201 females with an average age of(48.8±16.6)years.Hepatocellular type accounted for 64.06%(1911/2983),cholestatic type 6.57%(196/2983)and mixed type 29.37%(876/2983).Severity levels of DILI 1,2,3 and 4 grade accounted for 63.66%(1899/2983),25.01%(746/2983),8.88%(265/2983)and 2.45%(73/2983),respectively.After 1,2,3 and 4 weeks of treatment,normalization rates of ALT were 65.04%,83.47%,94.90%and 98.22%,respectively.There were significant differences in ALT and AST among different DILI severity levels before treatment(P<0.001),but without significant difference after one week of treatment(P>0.05).ALT normalization rate showed significant difference between ALT 3 time to 5 times ULN group and ALT≥5 times ULN group after 1 week and 2 weeks of treatment(χ^(2)=97.9,31.4;P<0.001).The characteristic variables were screened by LASSO regression.Through multivariate logistic regression analysis,6 variables were indentified for affecting the normalization rate of ALT at one week of treatment,including low-dose bicyclol(25 mg/dose),cholestatic type,ALT≥5 times ULN at the baseline,hypertension,abdominal distention and gum bleeding.Based on these factors,nomogram prediction model was constructed.With an AUC of 0.656(95%CI:0.631-0.682).Conclusions Bicyclol tablets have good efficacy in patients with mild and moderate ATB-DILI,and Nomogram model is valuable for predicting normalization rate of ALT in a short time after treatment.
作者
秦娅莉
梁清涛
陈晓红
张偲
郝晓晖
邱丽华
欧阳兵
黄有为
欧文卉
杨景
李军
陈静
段鸿飞
Qin Yali;Liang Qingtao;Chen Xiaohong;Zhang Si;Hao Xiaohui;Qiu Lihua;Ouyang Bing;Huang Youwei;Ou Wenhui;Yang Jing;Li Jun;Chen Jing;Duan Hongfei(School of Public Health,the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,Guiyang 561113,Guizhou,China;Department of Tuberculosis,Public Health Treatment Center of Guiyang City,Guiyang 550001,Guizhou,China;Department of Tuberculosis,Beijing Chest Hospital,Capital Medical University/Beijing Tuberculosis&Thoracic Tumor Research Institute,Beijing 101149;Department of Tuberculosis,Fuzhou Pulmonary Hospital of Fujian Province,Fuzhou 350008,Fujian,China;Department of Infectious Diseases,Rugao People′s Hospital,Rugao 226500,Jiangsu,China;Department of Tuberculosis,Shanghai Pulmonary Hospital,Tongji University,Shanghai 200433,China;Department of Tuberculosis,Shandong Public Health Clinical Center,Jinan 250013,Shandong,China;Department of Tuberculosis,The Third People′s Hospital of Kunming City,Kunming 650041,Yunan,China;Department of Infectious Diseases,Nanhua Hospital Affiliated to Nanhua University,Hengyang 421002,Hunan,China;Department of Infectious Diseases,Xiangdong Hospital,Hunan Normal University,Zhuzhou 412200,Hunan,China;Department of Infectious Diseases,The Central Hospital of Yueyang,Yueyang 414000,Hunan,China)
出处
《中国医学前沿杂志(电子版)》
北大核心
2025年第6期55-62,共8页
Chinese Journal of the Frontiers of Medical Science(Electronic Version)
