|
摘要：
|
|
摘要：目的 探讨药物性肝损伤（drug-induced liver injury，DILI）的临床特征及慢性化影响因素。
方法 前瞻性连续入组2018年8月至2019年3月首都医科大学附属北京地坛医院收治的肝功能异常，
随后通过RUCAM评分临床诊断为DILI的患者，根据服药种类分为中草药组、心血管药组、非甾
体类抗炎药（non-steroidal anti-inflammatory drugs，NSAIDs）组、抗感染药组、其他药组，检测
患者基线、随访3个月和6个月丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天门冬氨酸
氨基转移酶（aspartate aminotransferase，AST）、总胆红素（total bilirubin，TBil）、直接胆红素
（direct bilirubin，DBil）、γ-谷酰转肽酶（γ-glutamyl transpeptidase，γ-GT）、碱性磷酸酶（alkaline
phosphatase，ALP）、白蛋白（albumin，ALB）、总胆汁酸（total bile acid，TBA）、血常规、凝血
酶原活动度（prothrombin activity，PTA）、国际标准化比值（international normalized ratio，INR）、
血清甲胎蛋白（alpha-fetoprotein，AFP）、特种蛋白、抗核抗体（antinuclear antibody，ANA）、抗
平滑肌抗体（antismooth muscle antibody，ASMA）、抗线粒体抗体（anti-mitochondrial antibody，
AMA）及肝肾微粒体抗体（liver-kidney microsomal antibody，LKM）。采用Logistic单因素和多因素
回归分析DILI慢性化的危险因素。采用受试者工作特征（receiver operator characteristic，ROC）曲线
分析各因素的诊断效能。结果 共入组74例DILI患者，其中男19例，女55例，肝细胞损伤型占59.5%
（44/74），胆汁淤积型占24.3%（18/74），混合型占16.2%（12/74）。中草药组36例，心血管药组6
例，NSAIDs组10例，抗感染药组7例，其他药组15例，NSAIDs组患者在发病初期肝损伤较重，基线
ALT（中位数：537.50 U/L vs 277.50 U/L）、AST（中位数：592 U/L vs 182.50 U/L）水平显著高于中
草药组（z = -2.130，P = 0.033；z = -2.663，P = 0.007），TBil（中位数：96 U/L vs 19 U/L vs 23 U/L）
水平显著高于中草药组和心血管药组（P均＜ 0.05）。随访6个月时，22.97%（17/74）患者出现慢性
化，其中NSAIDS组慢性化占比最高，为30%（3/10）。Logistic单因素及多因素分析表明，基线TBil、
基线DBil、基线TBA、用药种类与基线ANA阳性是DILI慢性化的独立危险因素（P均＜ 0.05）。基线
TBil、DBil和TBA联合诊断DILI患者慢性化的ROC曲线下面积、敏感度和特异度均较单独诊断高；联合
诊断的ROC曲线下面积为0.925（95%CI：0.863～0.986，P = 0.032）。结论 基线TBil、DBil和TBA是DILI慢
性化的独立预测指标，联合诊断DILI慢性化的ROC曲线下面积、敏感性和特异度均较单独诊断时高。
|
|
Abstract: Objective To analyze the clinical characteristics and chronic factors in patients with drug-
induced liver injury (DILI). Methods Patients with abnormal liver function and then diagnosed as DILI by
RUCAM scale in Beijing Ditan Hospital, Capital Medical University from August 2018 to March 2019 were
prospectively continuity recruited. Patients were divided into Chinese herbal medicine group, cardiovascular
medicine group, non-steroidal anti-inflammatory drugs (NSAIDs) group, anti-infection drugs group and other
drugs group according to the types of drugs. Alanine aminotransferase (ALT), aspartate aminotransferase
(AST), total bilirubin (TBil), direct bilirubin, (DBil), γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase
(ALP), albumin (ALB), total bile acid (TBA), prothrombin activity (PTA), international normalized ratio
(INR), alpha-fetoprotein (AFP), antinuclear antibody (ANA), antismooth muscle antibody (ASMA), anti-
mitochondrial antibody (AMA), and liver-kidney microsomal antibody (LKM) of patients at baseline, 3
months and 6 months were detected. Risk factors of chronic DILI were analyzed by Logistic single and
multivariate regression analysis. Receiver operator characteristic (ROC) curve was used to analyze the
diagnostic efficacy of each factor. Results A total of 74 patients with DILI were enrolled, including 19 males
and 55 females. The hepatocyte injury type accounted for 59.5% (44/74), the cholestasis type accounted for
24.3% (18/74), and the mixed type accounted for 16.2% (12/74). There were 36 cases in herbal medicine
group, 6 cases in cardiovascular medicine group, 10 cases in NSAIDs group, 7 cases in anti-infective
medicine group, and 15 cases in the other medicine groups. Patients in NSAIDs group had severe liver damage
at the beginning of the onset, the baseline ALT (median: 537.50 U/L vs 277.50 U/L) and AST (median: 592 U/L vs
182.50 U/L) were significantly higher than those in herbal medicine group (z = -2.130, P = 0.033; z = -2.663,
P = 0.007), the levels of TBil (median: 96 U/L vs 19 U/L vs 23 U/L) were significantly higher than those in
herbal medicine group and cardiovascular medicine group (all P ＜ 0.05). At 6 months of follow-up, 22.97%
(17/74) developed chronicity, of which the chronicity rate was the highest in NSAIDS group [30% (3/10)].
Logistic univariate and multivariate analysis showed that baseline TBil, baseline DBil, and baseline TBA
were independent risk factors for chronic DILI (all P ＜ 0.05). The area under the ROC curve, sensitivity
and specificity of combined diagnosis of baseline TBil, DBil, and TBA in diagnosis of chronic DILI were
higher than those of diagnosed separately, the area under the ROC curve for combined diagnosis was 0.925
(95%CI = 0.863～0.986, P = 0.032). Conclusions Baseline TBil, DBil, and TBA were independent predictors
of chronicity of DILI. The area under the ROC curve, sensitivity and specificity of combined diagnosis of
baseline TBil, DBil, and TBA levels were higher than those of diagnosed separately.
|
|
基金项目：
|
|
|
|
作者简介：
|
|
|
|
参考文献：
|
|
|
|
服务与反馈：
|
|
【文章下载】【加入收藏】
|
|
|
|