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急、慢性药物性肝损伤临床特征的对比分析
A comparative analysis of the clinical features of acute and chronic drug-induced liver injury
文章发布日期:2020年06月08日  来源:  作者:纪童童,陆海英,谭宁,等  点击次数:300次  下载次数:157次

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【摘要】:目的 回顾性对比分析急、慢性药物性肝损伤(DILI)临床特征的异同。方法 收集2015年1月-2018年12月在北京大学第一医院感染疾病科诊断为DILl的183例住院患者的临床资料,分为急性组(n=138)和慢性组(n=45)。收集患者基本情况、基础疾病、可疑药物用药史、过敏史、饮酒史、症状体征、实验室检查、影像学检查、肝组织病理检查、治疗、转归等资料。所有诊断为DILI的患者均进行RUCAM、肝损伤类型及严重程度分级评分。符合正态分布的计量资料2组间比较采用t检验,不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ2检验;DILI慢性化的影响因素分析采用logistics回归分析。结果 中草药导致DILI在急、慢性组的病例数为105(76.1%)和33(73.3%),抗菌素所致的为15(10.9%)和5(11.1%)。2组患者性别(χ2=4.774,P=0.029)、肝损伤类型(χ2=9.848,P=0.020)及DILI严重程度分级(χ2=8.012,P=0.046)情况比较差异均有统计学意义;慢性组RUCAM评分≤6的病例数占77.8%,而急性组RUCAM评分≥6的病例数占79.7%,2组比较差异有统计学意义(χ2=21.471,P=0.002)。2组间PLT、ALT、AST、DBil、Cr水平,以及ANA阳性检出率和SMA阳性检出率比较差异均有统计学意义(P值均<0.05)。与急性组比较,慢性组潜伏期更长、合并肝硬化及治疗无效病例的百分比更高(P值均<0.05);2组患者激素治疗和激素+硫唑嘌呤治疗百分比比较差异均有统计学意义(χ2值分别为27.109、27.408,P值均<0.05)。急、慢DILI组分别有16例(11.6%)和7例(15.6%)为AIH样DILI;分别有29例和27例完成了肝组织病理检查,其中肝组织病理检查不能明确病因的分别有2例(6.9%)和6例(22.2%)。ALT (OR=0.997,95%CI: 0.985~0.999,P=0.003)、PLT(OR=0.997,95%CI: 0.986~0.998,P=0.013)是DILI慢性化的独立预测指标。结论 与急性DILI相比,慢性DILI中女性患者比例更高;诊断较困难,潜伏期长,胆汁淤积型比例及自身抗体的检出率较高,更需要糖皮质激素和免疫抑制治疗,预后较差。ALT、PLT可能是DILI慢性化的独立预测指标。
【Abstract】:Objective To investigate the similarities and differences in the clinical features of acute versus chronic drug-induced liver injury (DILI). Methods Clinical data were collected from 183 patients who were hospitalized and diagnosed with DILI in Department of Infectious Diseases, Peking University First Hospital, from January 2015 to December 2018, and the patients were divided into acute group with 138 patients and chronic group with 45 patients. Related data were collected, including general information, underlying diseases, history of suspected drugs, history of allergy, drinking history, symptoms and signs, laboratory examination, radiological examination, liver biopsy, treatment, and prognosis. Roussel Uclaf Causality Assessment Method (RUCAM) score was determined for all patients diagnosed with DILI, and the type and severity of liver injury were determined. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; a logistic regression analysis was used to investigate the influencing factors for chronicity of DILI. Results Among the 138 patients in the acute group, 105 (76.1%) had DILI caused by Chinese herbal medicine and 15 (10.9%) had DILI caused by antibiotics, while among the 45 patients in the chronic group, 33 (73.3%) had DILI caused by Chinese herbal medicine and 5 (11.1%) had DILI caused by antibiotics. There were significant differences between the two groups in sex (χ2=4.774, P=0.029), type of liver injury (χ2=9.848, P=0.02), and severity of DILI (χ2=8.012, P=0.046); 77.8% of the patients in the chronic group had a RUCAM score of ≤6, while 79.7% of the patients in the acute group had a RUCAM score of ≥6, and there was a significant difference between the two groups (χ2=21.471, P=0.002). There were significant differences between the two groups in platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase, direct bilirubin, creatinine, detection rate of ANA, and detection rate of SMA (all P<0.05). Compared with the acute group, the chronic group had a significantly longer incubation period and a significantly higher proportion of patients with liver cirrhosis or no response to treatment (all P<0.05); there was a significant difference between the two groups in the proportion of patients treated with glucocorticoids (χ2=27.109, P<0.05) or glucocorticoids combined with azathioprine (χ2=27.408, P<0.05). A total of 16 patients (11.6%) in the acute group and 7 (15.6%) in the chronic group had autoimmune hepatitis-like DILI; 29 patients in the acute group underwent liver pathological examination, among whom 2(6.9%) had an unknown cause, while 27 patients in the chronic group underwent liver pathological examination, among whom 6(22.2%) had an unknown cause. ALT (odds ratio [OR]=0.997, 95% confidence interval [CI]: 0.985-0.999, P=0.003) and PLT (OR=0.997, 95%CI: 0.986-0.998, P=0.013) were independent predictive factors for chronicity of DILI. Conclusion Compared with acute DILI, chronic DILI is more common in female patients and is difficult to diagnose, with a long incubation period, a higher proportion of patients with cholestasis type, and a higher detection rate of autoantibody, and it requires glucocorticoid and immunosuppressive therapy more and tends to have poorer prognosis. ALT and PLT may be independent predictive factors for the chronicity of DILI.
【关键字】:化学性与药物性肝损伤; 疾病特征; 糖皮质激素类
【Key words】:chemical and drug induced liver injury; disease attributes; glucocorticoids
【引证本文】:JI TT, LU HY, TAN N, et al. A comparative analysis of the clinical features of acute and chronic drug-induced liver injury[J]. J Clin Hepatol, 2020, 36(7): 1556-1561. (in Chinese)
纪童童, 陆海英, 谭宁, 等. 急、慢性药物性肝损伤临床特征的对比分析[J]. 临床肝胆病杂志, 2020, 36(7): 1556-1561.

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