胆管细胞损伤型药物性肝损伤病理与临床生化特征分析

Clinical and biochemical features of bile duct injury type of drug-induced liver injury

目的分析胆管细胞损伤型药物性肝损伤(DILI)各病理亚型的病理与临床生化学特点,进而验证DILI病理分类的划分价值及意义。方法采用回顾性研究方法,收集2006年1月-2016年1月石家庄市第五医院及2003年10月-2014年6月中日友好医院胆管细胞损伤型DILI患者112例。依据不同病理亚型分为混合性肝炎组(混合组)40例,淤胆性肝炎组(淤胆组)40例,单纯性淤胆组(单纯组)32例。分析各亚型用药种类、病程、R值、肝生化学各指标高峰值及变化趋势、以及肝生化各指标达峰时间及恢复时间等特点。计量资料多组间比较采用独立样本Kruskal-Wallis H非参数检验,两组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ2检验。结果引起DILI的药物分类中,中药及西药在胆管细胞损伤型DILI约各占一半。中药主要包括治疗骨关节病、椎间盘膨出、脱发、排石利胆、壮阳、皮肤病等药物,其中淤胆组中药所占比例最高,高达65%(26例),混合组为40%(16例),单纯组为40.6%(13例);引起DILI前两位的西药分别为抗生素、解热镇痛药。混合组、淤胆组、单纯组ALT峰值、AST峰值及R值依次降低,差异均有统计学意义(χ2值分别为54.77、44.21、51.95,P值均<0.001),其他肝生化指标峰值在三亚型组之间差异均无统计学意义(P值均>0.05)。混合组及淤胆组具有TBil达峰时间滞后于ALT达峰时间的特点。病程、肝生化各指标达峰及恢复时间三组间比较,差异均无统计学意义(P值均>0.05)。结论胆管细胞损伤型DILI各亚型具有各自独特的临床及生化学特点,了解该特点可以更准确的判断临床分型及病变损伤靶点及程度。

Objective To investigate the pathological and biochemical features of each pathological subtype of bile duct injury type of drug-induced liver injury(DILI),and to verify the value and significance of pathological classification of DILI.Methods A retrospective analysis was performed for the clinical data of 112 patients with bile duct injury type of DILI who were admitted to Shijiazhuang Fifth Hospital from January 2006 to January 2016 and China-Japan Friendship Hospital from October 2003 to June 2014.According to the pathological subtype,the patients were divided into mixed hepatitis group with 40 patients,cholestatic hepatitis group with 40 patients,and simple cholestasis group with 32 patients,and the three groups were compared in terms of types of drugs used,course of disease,R value,and peak values,changing trend,time to peak,and recovery time of liver biochemical indices.The independent-samples Kruskal-Wallis H test was used for comparison of continuous data between multiple groups,and the Mann-Whitney U test was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between groups.Results Among the drugs inducing DILI,traditional Chinese medicine and Western medicine each accounted for half of the cases of bile duct injury type of DILI.Traditional Chinese medicine mainly included the drugs for osteoarthropathy,intervertebral disc bulge,alopecia,calculus-removing and cholagogic treatment,Yang-tonifying therapy,and skin diseases;26 patients(65%)in the cholestatic hepatitis group had DILI caused by traditional Chinese medicine,while 16 patients(40%)in the mixed hepatitis group and 13(40.6%)in the simple cholestasis group had such DILI.Antibiotics and antipyretic and analgesic drugs were the most common Western medicines for DILI.The mixed hepatitis group had the highest peak values of ALT and AST and R value,followed by the cholestatic hepatitis group and the simple hepatitis group(χ2=54.77,44.21,and 51.95,all P<0.001),and there were no significant differences in the peak values of the other liver biochemical parameters between the three groups(all P>0.05).In the mixed hepatitis group and the cholestatic hepatitis group,the time to peak of TBil was longer than that of ALT.There were no significant differences in course of disease,time to peak of liver biochemical parameters,and recovery time between the three groups(all P>0.05).Conclusion Each subtype of bile duct injury type of DILI has unique clinical and biochemical features,and an understanding of such features may help to accurately judge clinical typing,pathological changes of targets,and degree of injury.