Perhexiline Maleate-Associated Hepatic Injury Prevalence and Characteristics

Abstract

In order to assess the prevalence and characteristics of perhexiline maleate (PM)-associated hepatic injury, we have conducted a study in 46 patients on PM therapy (100-400 mg/day) for angina pectoris. Hepatomegaly was found in 6 patients. The prevalence of abnormal liver function tests were: (1) fractional clearance of BSP, 74%; (2) fasting total serum bile acids, 57% and (3) serum transaminases, 30%. The other tests were abnormal in less than 10% of the patients. A significant increase in BSP clearance was observed 3-6 months after PM withdrawal. Conversely, while treatment continued unchanged BSP clearance significantly decreased. A pathological and histochemical study of the liver was performed in 11 patients with an abnormal BSP clearance. Diffuse micro- and macrovacuolar fatty change and hepatocellular hyperplasia were found in all the specimens. In addition to an excess of triglycerides, the histochemical study revealed an abnormal amount of phospholipids and/or gangliosides in some liver specimens. This study shows that PM induces liver injury in a high proportion of patients receiving the drug. This liver injury is: (1) usually clinically latent; (2) characterized by an impairment of the hepatic transport of BSP or bile acids and by the presence of an abnormal amount of various classes of lipids in the liver, and (3) progressive while PM therapy continues.