Dabigatran-induced acute liver injury in older patients: case report and literature review

Abstract

Objective. Dabigatran, a direct inhibitor of thrombin, represents an effective alternative to warfarin. Despite the good tolerance and predictable pharmacokinetic profile, dabigatran may be associated to adverse reactions, including gastrointestinal disorders. Here we report on a case of hepatotoxicity along with an extensive revision of the available literature on dabigatran induced liver injury.Methods & results. An 84 years old man attended the Emergency Department after experiencing fatigue for a few days. He suffered from atrial fibrillation and had been initiated on dabigatran (110 mg bid) in the last four weeks. Clinical examination revealed tachycardia, scleral icterus in the absence of signs of chronic hepatic disease. Blood chemistry showed altered liver function tests: AST 809 IU/L, ALT 1629 IU/L, total bilirubin 2.42 mg/dL, gGT 381 IU/L, ALP 388 IU/L, LDH 552 IU/L. Screening laboratory investigations for infectious, autoimmune or metabolic hepatotoxic pathology were unremarkable. The abdominal ultrasound examination excluded vascular causes, revealing non-homogeneous echo-structure consistent with mild hepatic steatosis. At admission to our Geriatric ward dabigatran was discontinued and fondaparinux was introduced. Resolution of the hepatitis and normalization of blood chemistry was observed within two weeks. Few cases are described regarding hepatotoxicity likely caused by the recent onset of treatment with dabigatran. Conclusions. DOACs associated hepatotoxicity is rare but potentially harmful and should be kept in mind, especially in comorbid patients with unexplained liver injury. The mechanism of liver injury during dabigatran therapy is unknown and, not related to cytochrome P450 enzymes since the drug does not affect CYP450 activity.