Omeprazole is widely used to treat acid-related disorders. The overall incidence of adverse events is low; most events, including diarrhea, flatulence, constipation, and abdominal pain, involve the gastrointestinal tract [1, 2]. Isolated reports have described other adverse effects, including fulminant hepatic failure [3]. We report a case of recurrent severe acute hepatitis induced by omeprazole.

A 30-year-old man with advanced renal failure secondary to diabetic nephropathy was admitted to our hospital in September 1995 because of epigastric pain, nausea, and darkened stools. He had been taking ranitidine, calcium carbonate, furosemide, and nifedipine for the previous 4 months. On admission, physical examination findings were irrelevant, and results of liver function tests and abdominal ultrasonography were normal. Endoscopy showed erosive gastritis and a duodenal ulcer. Ranitidine therapy was stopped and omeprazole, 20 mg once daily, was prescribed. Nine days later, the patient reported abdominal pain. Physical examination showed diffuse tenderness and hepatomegaly. Serum chemistry showed acute liver injury (aspartate aminotransferase level, 1788 U/L; alanine aminotransferase level, 1294 U/L). Prothrombin time was normal. Results of hepatitis serologic testing for hepatitis A, B, and C virus; Epstein-Barr virus; herpes simplex virus; and cytomegalovirus were negative. Immunologic studies, including measurement of immunoglobulins; rheumatoid factor; complement (C3 and C4); and antinuclear, antineutrophilic, antimitochondrial, and anti-smooth-muscle antibodies, had normal or negative results. Ferritin, ceruloplasmin, and ₁-antitrypsin levels were also normal.

Omeprazole therapy was discontinued, and the liver function test results returned to normal within 4 weeks. Six months later, the patient presented with symptoms suggestive of esophagitis. Findings on liver function tests were normal. Omeprazole therapy was then started. Blood chemistry done 1 week later indicated acute liver injury (aspartate aminotransferase level, 954 U/L; alanine aminotransferase level, 762 U/L). Results of hepatitis serologic testing and immunologic studies were normal. Omeprazole therapy was stopped, and liver function test results gradually returned to normal.

Drug-induced hepatotoxicity is a major cause of iatrogenic diseases. Because the liver is central to the metabolic disposition of almost all drugs, drug-induced liver injury is a potential complication of nearly every medication that is prescribed [4]. Omeprazole was the only new medication in our patient. Furthermore, the time association between omeprazole therapy and the patient's clinical symptoms and laboratory alterations, as well as the positive response to rechallenge, strongly suggests a cause-and-effect relation. The mechanism for omeprazole-induced hepatotoxicity is probably idiosyncratic because an allergic or a direct toxic reaction is unlikely.