中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2012年
3期
185-189
,共5页
赖荣陶%王晖%桂红莲%叶敏贞%戴维佳%项晓刚%赵钢德%王伟静%谢青
賴榮陶%王暉%桂紅蓮%葉敏貞%戴維佳%項曉剛%趙鋼德%王偉靜%謝青
뢰영도%왕휘%계홍련%협민정%대유가%항효강%조강덕%왕위정%사청
药物性肝损伤%病理学%组织学
藥物性肝損傷%病理學%組織學
약물성간손상%병이학%조직학
Drug-induced liver injury%Pathology%Histology
目的 探讨当前引起药物性肝损伤的主要药物种类,了解患者的临床特征及肝脏组织学改变情况,以期为临床诊断提供思路. 方法 收集2008年4月至2010年4月连续收治临床诊断为药物性肝损伤(DILI)的138例患者资料,入选标准为依据Roussel Uclaf因果关系评估法评分值≥6分.依临床分型分为3组:肝细胞损伤型组、胆汁淤积型组和混合型组.3型诊断标准为:(1)肝细胞损伤型:[ALT/正常值上限(ULN)]/(碱性磷酸酶/ULN)≥5；(2)胆汁淤积型:(ALT/ULN)/(碱性磷酸酶/ULN)≤2；(3)混合型:2＜(ALT/ULN)/(碱性磷酸酶/ULN)＜5.分别统计其一般资料、临床表现、生物化学及免疫学指标,并对其中66例行肝活组织检查患者的肝脏组织学改变进行分析.多组均数比较采用单因素方差分析,多组非参数统计采用Kruskal-Wallis检验,两组比较的非参数统计采用Wilcoxon秩和检验,临床与病理学分型的一致性比较采用kappa检验,两样本率的比较采用x2检验和Fisher' s精确概率法.结果 本研究中致肝损伤药物主要有中草药(包括中成药,占53.6％)、抗微生物药(8.0％)以及保健品(6.5％).依据血清生物化学指标进行临床分型,其与病理损伤分型的一致性(kappa=0.63,P＜0.05)优于发病时临床分型与病理损伤分型的一致性(kappa=0.25,P＜ 0.05).DILI患者的病理学特征主要有大泡性脂肪变性、小泡性脂肪变性、胆汁淤积、肝细胞凋亡、上皮样肉芽肿、嗜酸性粒细胞及嗜中性粒细胞浸润,淋巴细胞、浆细胞浸润及铁沉着.胆汁淤积型及混合型患者肝组织学改良HAI炎症坏死评分和Ishak纤维化评分均高于肝细胞损伤组(P值均＜0.05).结论 中草药(包括中成药)是导致肝损伤的重要原因；同一时相临床分型与病理损伤分型有较好的一致性；胆汁淤积型及混合型肝损伤患者的组织炎症和纤维化评分均高于肝细胞损伤组,结合临床表现与病理特征可有助于DILI的诊断.
目的 探討噹前引起藥物性肝損傷的主要藥物種類,瞭解患者的臨床特徵及肝髒組織學改變情況,以期為臨床診斷提供思路. 方法 收集2008年4月至2010年4月連續收治臨床診斷為藥物性肝損傷(DILI)的138例患者資料,入選標準為依據Roussel Uclaf因果關繫評估法評分值≥6分.依臨床分型分為3組:肝細胞損傷型組、膽汁淤積型組和混閤型組.3型診斷標準為:(1)肝細胞損傷型:[ALT/正常值上限(ULN)]/(堿性燐痠酶/ULN)≥5；(2)膽汁淤積型:(ALT/ULN)/(堿性燐痠酶/ULN)≤2；(3)混閤型:2＜(ALT/ULN)/(堿性燐痠酶/ULN)＜5.分彆統計其一般資料、臨床錶現、生物化學及免疫學指標,併對其中66例行肝活組織檢查患者的肝髒組織學改變進行分析.多組均數比較採用單因素方差分析,多組非參數統計採用Kruskal-Wallis檢驗,兩組比較的非參數統計採用Wilcoxon秩和檢驗,臨床與病理學分型的一緻性比較採用kappa檢驗,兩樣本率的比較採用x2檢驗和Fisher' s精確概率法.結果 本研究中緻肝損傷藥物主要有中草藥(包括中成藥,佔53.6％)、抗微生物藥(8.0％)以及保健品(6.5％).依據血清生物化學指標進行臨床分型,其與病理損傷分型的一緻性(kappa=0.63,P＜0.05)優于髮病時臨床分型與病理損傷分型的一緻性(kappa=0.25,P＜ 0.05).DILI患者的病理學特徵主要有大泡性脂肪變性、小泡性脂肪變性、膽汁淤積、肝細胞凋亡、上皮樣肉芽腫、嗜痠性粒細胞及嗜中性粒細胞浸潤,淋巴細胞、漿細胞浸潤及鐵沉著.膽汁淤積型及混閤型患者肝組織學改良HAI炎癥壞死評分和Ishak纖維化評分均高于肝細胞損傷組(P值均＜0.05).結論 中草藥(包括中成藥)是導緻肝損傷的重要原因；同一時相臨床分型與病理損傷分型有較好的一緻性；膽汁淤積型及混閤型肝損傷患者的組織炎癥和纖維化評分均高于肝細胞損傷組,結閤臨床錶現與病理特徵可有助于DILI的診斷.
목적 탐토당전인기약물성간손상적주요약물충류,료해환자적림상특정급간장조직학개변정황,이기위림상진단제공사로. 방법 수집2008년4월지2010년4월련속수치림상진단위약물성간손상(DILI)적138례환자자료,입선표준위의거Roussel Uclaf인과관계평고법평분치≥6분.의림상분형분위3조:간세포손상형조、담즙어적형조화혼합형조.3형진단표준위:(1)간세포손상형:[ALT/정상치상한(ULN)]/(감성린산매/ULN)≥5；(2)담즙어적형:(ALT/ULN)/(감성린산매/ULN)≤2；(3)혼합형:2＜(ALT/ULN)/(감성린산매/ULN)＜5.분별통계기일반자료、림상표현、생물화학급면역학지표,병대기중66례행간활조직검사환자적간장조직학개변진행분석.다조균수비교채용단인소방차분석,다조비삼수통계채용Kruskal-Wallis검험,량조비교적비삼수통계채용Wilcoxon질화검험,림상여병이학분형적일치성비교채용kappa검험,량양본솔적비교채용x2검험화Fisher' s정학개솔법.결과 본연구중치간손상약물주요유중초약(포괄중성약,점53.6％)、항미생물약(8.0％)이급보건품(6.5％).의거혈청생물화학지표진행림상분형,기여병리손상분형적일치성(kappa=0.63,P＜0.05)우우발병시림상분형여병리손상분형적일치성(kappa=0.25,P＜ 0.05).DILI환자적병이학특정주요유대포성지방변성、소포성지방변성、담즙어적、간세포조망、상피양육아종、기산성립세포급기중성립세포침윤,림파세포、장세포침윤급철침착.담즙어적형급혼합형환자간조직학개량HAI염증배사평분화Ishak섬유화평분균고우간세포손상조(P치균＜0.05).결론 중초약(포괄중성약)시도치간손상적중요원인；동일시상림상분형여병리손상분형유교호적일치성；담즙어적형급혼합형간손상환자적조직염증화섬유화평분균고우간세포손상조,결합림상표현여병리특정가유조우DILI적진단.
Objective To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI),in order to gain insights into potential diagnostic factors for DILI.Methods A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed.The responsible drug for each DILI case was recorded.The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI.Only cases that had scored as highly probable or probable ( ≥ 6 points by RUCAM) were included in this study.The patients' general condition,clinical manifestations,and serum biochemical and immunological parameters were assessed.Sixty-six of the patients underwent liver biopsy,and were assessed for liver pathological changes.Clinical and laboratory test data were collected and used to clasify the total 138 cases as hepatocellular injury,cholestatic,or mixed hepatocellular-cholestatic types.Results Within our patient population,the leading cause of DILI was Chinese herb medicine,accounting for 53.62％ of cases.Antibiotics were implicated in 7.97％ of cases,and dietary supplement in 6.52％ of cases.Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy ( ≥ 3 days after laboratory results) (kappa =0.63,P ＜ 0.05) than at the onset of DILI (kappa =0.25,P ＜ 0.05).All modified hepatic activity index (HAI)necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P ＜ 0.01 andP ＜ 0.05,respectively).Conclusion Chinese herbal medicine,dietary supplements and antibiotics were the main causes of DILI in our patient population.The clinical and histological features correlated well,especially at later stages of DILI.The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatoeellular injury type.Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.
