Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements.
Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements.
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DOI：
10.1002/hep.28967
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
U.S. Drug Induced Liver Injury Network Investigators
中科院分区：
文献类型：
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作者：
Bonkovsky HL;Kleiner DE;Gu J;Odin JA;Russo MW;Navarro VM;Fontana RJ;Ghabril MS;Barnhart H;Hoofnagle JH;U.S. Drug Induced Liver Injury Network Investigators
药物性肝损伤过程中的胆管丢失并不常见，但可能是胆管消失综合征的指征。在这项工作中，我们评估的频率，原因，临床特点和结果的情况下，药物引起的肝损伤与组织学证明胆管损失。对10年内纳入前瞻性数据库的所有接受肝活检的药物性肝损伤病例（n=363）进行胆管丢失评分，并评估临床和实验室特征、原因和结局。363例药物、草药或膳食补充剂相关肝损伤患者中有26例（7%）在肝活检中出现胆管丢失，其中14例为中度至重度（胆管汇管区<50%），12例为轻度（50-75%）。26例患者的临床表现各不相同，但最常见的临床模式是重度胆汁淤积性肝炎。涉及的药物包括阿莫西林/克拉维汀（n=3）、替莫唑胺（n=3）、各种草药产品（n=3）、阿奇霉素（n=2）和15种其他药物或膳食补充剂。与没有胆管缺失的人相比，胆管缺失的人更有可能出现慢性肝损伤（94%比47%），通常是胆汁淤积性的，有时甚至是严重的。5例患者死亡，另外2例患者因进行性胆汁淤积接受肝移植，尽管接受了皮质类固醇和熊去氧胆酸治疗。预后不良的最大预测因素是肝活检胆管丢失程度。急性胆汁淤积性肝炎时的胆管缺失是可能的胆管消失综合征的早期征兆，目前尚无已知的预防或治疗方法。
Bile duct loss during the course of drug induced liver injury is uncommon but can be an indication of vanishing bile duct syndrome. In this work we assess the frequency, causes, clinical features and outcomes of cases of drug induced liver injury with histologically proven bile duct loss. All cases of drug induced liver injury enrolled into a prospective database over a ten year period that had undergone liver biopsies (n=363) were scored for the presence of bile duct loss and assessed for clinical and laboratory features, causes and outcomes. 26 of the 363 patients (7%) with drug, herbal or dietary supplement associated liver injury had bile duct loss on liver biopsy which was moderate to severe (<50% of portal areas with bile ducts) in 14 and mild (50–75%) in 12. The presenting clinical features of the 26 cases varied, but the most common clinical pattern was a severe cholestatic hepatitis. The implicated agents included amoxicillin/clavulanate (n=3), temozolomide (n=3), various herbal products (n=3), azithromycin (n=2) and 15 other medications or dietary supplements. Compared to those without, those with bile duct loss were more likely to develop chronic liver injury (94% vs 47%), which was usually cholestatic and sometimes severe. Five patients died and two others underwent liver transplantation for progressive cholestasis despite treatment with corticosteroids and ursodiol. The most predictive factor of poor outcome was the degree of bile duct loss on liver biopsy. Bile duct loss during acute cholestatic hepatitis is an ominous early indicator of possible vanishing bile duct syndrome, for which at present there are no known means of prevention or therapy.