The natural history of histologically proved drug induced liver disease
The natural history of histologically proved drug induced liver disease
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作者：
Aithal, PG;Day, CP
背景——药物相关肝病的长期结果尚不清楚。目的——研究经组织学证实的药物引起的肝毒性的自然史。方法——从 1978-1996 年的医院记录中鉴定出 110 名肝活检编码为药物引起的肝病或病因不明的肝炎/胆汁淤积的患者。通过病例记录和组织学检查，确定 44 名患者患有明确的药物引起的肝毒性。四十名幸存的患者被邀请参加后续诊所。对所有患者重复进行病史、检查、全肝脏筛查、同位素和超声肝脏扫描。对肝功能检查异常的患者进行重复肝活检。结果-首次活检显示 24 名患者出现黄疸，17 名患者肝功能检查异常，3 名患者出现肝功能衰竭。抗生素（n=13）和非甾体抗炎药（n=11）是最常见的相关药物。最初的组织学显示，6 例患者患有急性肝炎，20 例患者患有慢性肝炎，18 例患者患有胆汁淤积。在 1-19 年（中位 5 年）随访中，13/33 (39%) 患者的肝脏血液检查和/或扫描显示持续显着异常。进行的五次重复肝活检中的三次显示出明显的异常。预测慢性肝病持续或发展的因素是纤维化和持续接触药物。结论-在肝功能和/或组织学异常的鉴别诊断中应考虑药物，因为未能撤回违规药物与持续性肝损伤的高风险相关。
Background-The long term outcome of drug related liver disease is unknown. Aims-To study the natural history of histologically proved drug induced hepatotoxicity.Methods-110 patients with liver biopsies coded either as drug induced liver disease or hepatitis/cholestasis of unknown aetiology were identified from hospital records 1978-1996. Review of case notes and histology identified 44 patients with definite drug induced hepatotoxicity. Forty surviving patients were invited to attend a follow up clinic. History, examination, full liver screen, and isotope and ultrasound liver scans were repeated in all patients. Repeat liver biopsies were offered to patients with abnormal liver tests.Results-Presentation at index biopsy was jaundice in 24 patients, abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and non-steroidal antiinflammatory drugs (n=11) were the most common drugs implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in 20, and cholestasis in 18. At 1-19 years (median 5 years) follow up, 13/33 (39%) patients had persistent significant abnormalities in their liver blood tests and/or scans. Three of the five repeat liver biopsies performed showed significant abnormalities. Factors predicting persistence or development of chronic liver disease were fibrosis and continued exposure to the drug.Conclusions-Drugs should be considered in the differential diagnosis of abnormal liver function and/or histology, as failure to withdraw the offending drug is associated with a high risk of persistent liver damage.