Unusual Cause of Acute Drug-Induced Hepatitis

Abstract

Rivaroxaban is an oral anticoagulant used in non-valvular A-fib, as well as treatment and prevention of DVT and pulmonary embolism (PE). We present a case of reversible acute liver injury; a rare adverse reaction of rivaroxaban. A 62-y.o. female presented to ER with a 2-week history of nausea, early satiety, dull aching RUQ pain, dark urine and normal colored stool. She has history of GERD and recurrent PE, the latest was a month earlier and she was started on rivaroxaban. She has no history of alcohol/acetaminophen use, substance abuse, liver disease, blood transfusion, recent travel or infection. The only positive physical exam finding was mild RUQ tenderness. Initial work up showed markedly elevated LFTs (table). Acute hepatitis profile, monospot test, acetaminophen/alcohol levels, EBV, CMV, CPK, TSH, urine/blood drug screen, autoimmune workup, liver ultrasound with Doppler, CT and MRI abdomen; all were negative. The patient was discharged home with GI follow-up. Few days later, she presented with worsening symptoms including dizziness, poor appetite and nausea. Repeat blood test showed worsening LFTs. Patient was admitted and started on supportive therapy while efforts to determine the cause of elevated LFTs continued. Rivaroxaban-induced acute liver injury was entertained. The drug was stopped and she was switched to enoxaparin for anticoagulation. Her LFTs and symptoms continued to improve over few months after her discharge. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between rivaroxaban use and acute liver injury. Rivaroxaban is a direct factor Xa inhibitor that may cause bleeding, rash and liver injury. Rivaroxaban is associated with moderate ALT elevation in 1.5% to 3% of patients. Most cases have an onset within 1 to 8 weeks of starting therapy. All patients recover 2 to 4 weeks after stopping rivaroxaban. Cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome due to rivaroxaban have not been reported in the literature. The exact mechanism of liver injury is unknown, but may be idiosyncratic or immunologic. Rivaroxaban is metabolized in the liver mainly by CYP3A4 and is susceptible to drug-drug interactions. Clinicians should be made aware of this rare side effect as early discontinuation of the drug is essential to prevent morbidity and even mortality. Future research is needed to determine if routine follow up of LFTs is advised in patients on rivaroxaban.2173 Figure 1 No Caption available.