Drug-Induced Liver Disease – A Review of 14 Cases

藥物引發之肝臟疾病－14例之分析

王鐘貴(Chung-Kwe Wang) ； 劉正典(Jean-Dean Liu) ； 林時宜(Shyr-Yi Lin) ； 廖麗瑛(Li-Ying Liao) ； 鄭乃源(Nai-Yuan Cheng) ； 王朝欣(Chaur-Shine Wang) ； 蕭泉豹(Chuan-Pau Siauw) ； 陳寶輝(Pao-Huei Chen)

《The Kaohsiung Journal of Medical Sciences》 11卷4期 (1995/04) Pp. 213-219

https://doi.org/10.6452/KJMS.199504.0213

摘要

藥物引發之肝疾病在臨床上並不罕見，在美國因黃疸而入院的病人中有2-5%是由藥物引起的。除了少數的省可直接於身體中測得或有特異的病理變化外，我們很難直接由臨床數據或病理檢查來診斷藥物引發之肝臟疾病，因之對臨床醫師是一大挑戰。在這篇報告中我們收集了14例被診斷為藥物引發之肝疾病同時曾在住院中接受肝臟生檢之病人，先確認其診斷之正確性，再試圖分析他們的臨床病史、生化數據及病理資料，以期對於不同型藥物引發之肝疾病找出某些相關性，以期對於不同型藥物引發之肝疾病找出某此相關性，來加強我們對此一疾病的認識。由1986自1991年我們收集14例病人，經排除急性A、B及慢性B型肝炎及C型肝炎、酗酒、藥物濫用、輸血、自體免疫疾病、代謝性疾病、肝外膽管阻塞、肝臟惡性腫瘤、懷孕、全身性惡性腫瘤、心臟血管疾病、最近開刀病史後，診斷為藥物引發之肝臟疾病。首先我們由病理資料將之分成三類-其中8例為細胞毒性型、4例為膽汁儲留型、2例為混合型。再利用法國派的方法來驗證我們診斷的正確性，然後分析臨床病史、生化數據及病理特徵，試圖找出其特點及相關性。
結果我們發現在細胞毒性型藥省引發之肝臟疾病之病例其鹼性磷酸酶皆小於正常的1.8倍，反之在膽汁儲留型則皆大於1.8倍，在氨轉酶的變化中則是膽汁儲留型皆小於正常的13.1倍而細胞毒性型則可由正常的2.2到118倍。在細胞毒性型病例中，若其氨轉酶小於正常的2.5倍，則病理特徵主要是脂肪儲留。粥樣壞死只見於氨轉酶大於正常20倍的病例。在膽汁儲留型病中，由口服避孕藥引起的病理所引起的則除了膽汁儲留，而由Chlorpromazine所引起的則除了膽汁儲留外可見門脈炎性反應。
由上可知鹼性磷酸酶及氨轉酶之變化有助於區別不同型的藥物引發之肝臟疾病，而在細胞毒性型的病例中，即使沒有做肝生檢，我們亦可以由生化數據的變化預測其肝臟損傷的程度，而在區分口服避孕藥或Chlorpromazine所引起的膽汁儲留型病例中，病理特徵可以區分這兩者的變化。

並列摘要

The clinical and pathological features of 14 cases of acute drug-induced liver disease (DILD) were analyzed using the French group method for drug reaction assessment. Among them, 8 were of cytotoxic type, 4 were of the cholestatic type and 2 were of the mixed type. Serum alkaline phosphatase (ALP) levels of the cytotoxic type DILD were all ＜1.8 times the normal value, while those of the cholestatic type DILD＞1.8 times (P＜0.05). The alanine aminotransaminase and aspartate aminotransaminase (ALT and AST) levels of the cholestatic type were all ＜13.1 times the normal value. We found that steatosis was the major feature in the cytotoxic type with ALT and AST ＜2.5 times the normal value. Piecemeal necrosis was noted only in all the cases with ALT and AST＞20 times the normal value. In the cholestatic type, the pathological features of the oral contraceptive-related DILD showed mainly cholestasis, whereas chlorpromazine-related DILD revealed additional portal inflammation. Meticulous taking of patient history and clinical assessment are mandatory for the diagnosis of DILD. The ALP levels were helpful in distinguishing different types of DILD. There are some correlations between biochemical changes and pathological features, and both are helpful in distinguishing different etiologies of DILD when the inciting drug is in doubt.

並列關鍵字

drug-induced liver disease ； cytotoxic type ； cholestatic type