Drug Induced Liver Injury Caused by Lorazepam

Abstract

This is the case of an 86 year old Hispanic male with medical history significant for dyslipidemia and diabetes mellitus type 2 who arrived to the emergency department due to abdominal pain of 1 month duration. Pain was 5/10 in severity, located in right upper quadrant, with radiation to epigastric region, worst after eating and with associated pruritus, dark urine, pale stools, anorexia and yellow sclera. He denied fever, chills, nausea, vomits, weight loss, early satiety, dysphagia, odynophagia, rectal bleeding or melena. Vital signs stable and physical examination only remarkable for jaundice. Laboratories remarkable for elevated liver enzymes (AST: 244 U/L and ALT: 300 U/L, ALP: 346 U/L and elevated total bilirubin 11.1 mg/dL, with direct predominance). R factor < 2, in favor of cholestatic injury. Toxicology screening and viral hepatitis serology was negative. Ultrasound and CT abdomen failed to show evidence of intra or extra hepatic duct dilatation. MRCP performed with limited findings due to motion blurring. Patient continued with abdominal pain, reason why ERCP was performed. Official report showed no evidence of intra or extra hepatic duct dilation. After above workup performed, a diagnosis of possible Drug Induced Liver Injury (DILI) was entertained. Upon record review and medication reconciliation, patient reported recent use of Lorazepam in view of wife's demise. In view of persistent elevation of hepatic enzymes, liver biopsy of the right lobe was performed. Pathology report revealed moderate lymphocytic infiltrate without evidence of cholangitis, canalicular cholestasis and macrovesicular steatosis (approximately 20%) suggestive of drug-induced etiology. Lorazepam was considered culprit of DILI, with a calculated RUCAM score of 7 (probable). Medication was discontinued and liver function improved markedly. Drug-induced liver injury can develop following the use of many drugs. The mechanism of hepatotoxicity is varied, dose depended or idiosyncratic. Currently it has an estimated annual incidence between 10 and 15 per 10,000 to 100,000 persons exposed to prescription medications and for approximately 10 percent of all cases of acute hepatitis. In the United States, it is the most common cause of acute liver failure. High index of suspicion should be present in patients with these clinical manifestations. A thorough drug history should be taking for all patients as prompt cessation of the offending agent may produce a rapid recovery.