Can omeprazole induce severe liver damage?/nBackground: A 45-year-old male patient was treated with

Fråga: Can omeprazole induce severe liver damage? Background: A 45-year-old male patient was treated with omeprazole (Losec, 20 mg daily) for two weeks due to unspecified gastritis. A fulminant hepatitis developed and a liver transplantation was planned. The patient refused the transplantation and received only conservative therapy which initially showed a gradual recovery. Now the situation has worsened again and liver enzyme levels are persistantly high. The etiology is totally unknown and all virological tests performed so far have been negative. The patient did not use any other drugs than omeprazole but took one paracetamol tablet during the two week therapy with omeprazole.

Sammanfattning: A few cases of severe liver damage or fulminant hepatitis have been associated with the use of omeprazole. Knowing the extremely wide use of the compound the causal relationship cannot, however, be considered certain.

Svar: Omeprazole has been associated with adverse liver effects. Transient liver transaminase increases have been reported but there are also a few cases of hepatitis or severe liver damage described. A fulminant fatal hepatic failure after a 17 day-treatment with omeprazole was published in 1992 (1). The patient was a 62-year-old male office worker with no risk factors for viral hepatitis. Centrizonal necrosis was demonstrated in the autopsy and possible involvement of the cytochrome P450 mixed oxidase system in production of a toxic metabolite was speculated by the authors. The patient was also on atenolol, diltiazem and aspirin, though omeprazole was the only new medication. The possible mechanism for hepatotoxicity to omeprazole is unknown.

In the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) there were 10 cases of adverse liver effects associated with the use of omeprazole (2). These were usually mild liver transaminase increases but one fatal liver necrosis has been reported. This patient had also taken paracetamol and supposedly alcohol before hospital admission. Paracetamol was considered the causative agent in this case. In the WHO adverse drug reactions database there were totally 527 reports of liver related side effects associated with the use of omeprazole (3). Of these 9 were hepatic necrosis and 9 hepatic failures, and 8 deaths of these 18 cases were reported. The available information is very limited making it extremely difficult if not impossible to judge the possible causal relationship to omeprazole.

The case should be reported to the regional center at Huddinge Hospital of the SADRAC (4).