Acute liver injury associated with the use of ebrotidine, a new H2-receptor antagonist.

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作   者：

Andrade RJ;  Lucena MI;  Martin Vivaldi-R;  Fernandez MC;  Nogueras F;  Pelaez G;  Gomez Outes-A;  Garcia Escano-MD;  Bellot V;  Hervas A;  Cardenas F;  Bermudez F;  Romero M;  Salmeron J; 

作者机构：

University Hospital;  Spain. Andrade@uma.es;  Malaga;  Department of Gastroenterology;  School of Medicine; 

关键词：

中毒性;  Hepatitis;  肝炎;  Toxic;  Thiazoles;  噻唑类;  Histamine H2 Antagonists;  Benzenesulfonates;  苯磺酸盐类;  组胺H2拮抗剂; 

期刊名称：

Journal of Hepatology: The Journal of the European Association for the Study of the Liver

i s s n：

0168-8278

年卷期：

1999 年 31 卷 4 期

页   码：

641-646

页   码：

摘   要：

BACKGROUND/AIM: Ebrotidine is a new H2-receptor antagonist marketed in Spain in early 1997 and withdrawn in July 1998. We report 11 cases of acute liver injury related to ebrotidine and submitted to a Regional Registry of Hepatotoxicity between June 1997 and August 1998. METHODS: In all cases a structured protocol was used to ascertain the role of ebrotidine and to exclude other causes (viral, immunologic, metabolic) of liver injury. RESULTS: All patients showed clinical symptoms of acute hepatitis, with a marked increase in aminotransferase activities (ALT values ranging from 15 to 91 times the upper limit of normal). Total bilirubin values were also greatly increased (mean 16 mg/dl), and the liver injury was defined as hepatocellular. Features of hypersensitivity were absent. Liver biopsy was done in three patients. Histopathological examination revealed mainly centrozonal necrosis (two cases) or massive necrosis (one patient). Withdrawal of the drug was followed by a gradual improvement in liver dysfunction, except in one patient who developed fulminant hepatic failure and died. There was a positive response to rechallenge in one patient after an inadvertent drug administration. CONCLUSION: Ebrotidine therapy seems to be associated with severe acute liver injury, and therefore its benefit/risk ratio is unfavorable. The relative rareness and unpredictability of the injury, the lack of dose-relationship and the absence of hallmarks of drug allergy are suggestive of an idiosyncratic metabolic mechanism.