Chronic liver injury related to use of bentazepam: an unusual instance of benzodiazepine hepatotoxicity.

Liver injury induced by benzodiazepines is rare and is classified as an unpredictable or idiosyncratic hepatotoxic reaction. Early reports indicated that in most cases the pattern of liver injury was cholestatic. We describe three patients with persistent increases in liver transaminase levels after several weeks of treatment with bentazepam, a benzodiazepine marketed in Spain for anxiety disorders. In all cases withdrawal of the drug was followed by resolution of transaminase level abnormalities. A liver biopsy (done in one patient only) showed histological evidence of severe chronic active hepatitis. In conclusion, these findings, together with two previously published case reports, suggest that a benzodiazepine can cause chronic hepatitis and argue in favor of using liver function tests to monitor all patients taking bentazepam.

Effects of interferon-beta on plasma lipid and lipoprotein composition and post-heparin lipase activities in patients with chronic hepatitis C.

BACKGROUND: Interferon therapy has been shown to induce lipid abnormalities. AIM: We assessed the effects of interferon-beta on the lipoprotein profile and post-heparin lipase activities in 26 normolipaemic patients with chronic hepatitis C. METHODS: Interferon-beta was administered subcutaneously at doses of 6 x 106 U (units) three times a week, over 6 months, and lipoproteins and post-heparin lipases were measured at baseline and at the end of therapy. RESULTS: Plasma triglycerides increased by 21% due to preferential enrichment in those contained in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The concentration of cholesterol decreased slightly in the high density lipoprotein (HDL) subfractions. Lipoprotein lipase, but not hepatic lipase activity decreased by a 36%, and this change showed a significant negative correlation with changes in plasma triglycerides. Five patients (19.5%) responded to interferon-beta therapy. The lipoprotein profile was no different between responders and non-responders to therapy. CONCLUSIONS: Interferon-beta treatment in normolipaemic patients with chronic hepatitis C induced moderate disturbances in plasma lipoproteins, associated with inhibition of lipoprotein lipase activity.

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

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.

[Chronic cholestasis as a presentation form of portal cavernoma]. / Colestasis crónica como forma de presentación de una cavernomatosis portal.

A 37 year-old-woman was evaluated in 1993 for a chronic asymptomatic cholestasis. An endoscopic retrograde cholangiopancreatography showed the biliary tract compressed, and a mesenteric angiogram disclosed that the cause of biliary obstruction was a portal cavernoma. In addition, large esophageal varices with "red spots" were observed at endoscopy. Propranolol and ursodeoxicolic acid were started and the patient has remained asymptomatic to date. The biliary features of portal cavernoma are reviewed, as well as its pathogenesis, diagnosis and management. Portal cavernoma should be considered in the differential diagnosis of chronic cholestasis.