engleski

Severe chronic intrahepatic cholestasis associated with orlistat

Introduction: Orlistat is an anti-obesity drug that acts locally in the gastrointestinal tract by inhibition of lipases. Systemic exposure to orlistat is minimal, and systemic adverse effects very rare. There have been several suggestions that it can cause severe hepatotoxicity. We present the first described case of chronic intrahepatic cholestasis related to orlistat use. Case report: A 59-year-old man presented with a 2 week history of malaise, jaundice and pruritus. Three months before he finished a treatment course with orlistat, losing 35 kg on his weight. No other drugs or herbal medications were being used at that time except for the years-long use of an ACE-inhibitor. Bilirubin level on presentation was 264 µ mol/L, with elevated alkaline phosphatase levels (290 U/L) and gamaglutamil transpeptidase levels (143 U/L), and normal other transaminase levels. The complete laboratory workup including viral, autoimmune and metabolic screen was negative, and imaging (ultrasound, CT) showed no abnormalities. Finally, liver biopsy revealed severe intracellular and extracellular cholestasis, without lobular and portal inflammation, and no hepatocyte necrosis. The patient received ursodeoxycholic acid and other symptomatic treatment. Prothrombin time remained normal throughout the hospitalization, while albumine levels declined to 27 g/L. After 35 days, bilirubin levels reached a plateau at 430 µ mol/L and then finally started to decline. Throughout the stay the patient remained in good condition, fully alert. After several more weeks, he was released from the hospital, and five months after the start of the disease the bilirubin levels returned to normal values. Conclusion: We diagnosed the patient with a severe form of drug-induced chronic intrahepatic cholestasis related to previous orlistat use. This case shows that the presumable aberrant metabolism of even those drugs with minimal systemic exposure can still lead to severe forms of drug-induced liver disease in a rare susceptible patient. Increasing prevalence of obesity and widespread use of anti-obesity drugs like orlistat adds to the importance of this observation.

orlistat; hepatotoxicity; intrahepatic cholestasis

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