Cefprozil as a Cause of Drug-Induced Liver Injury Leading to Acute-on-Chronic Liver Failure

Abstract

Cephalosporins are a widely used class of antibiotics due to their high therapeutic index, and broad spectrum of activity. Cases of cephalosporin drug induced liver injury (DILI) are rare [1]. We report a case of DILI caused by Cefprozil, a second generation cephalosporin leading to acute on chronic liver failure (ACLF). A 60 year old Caucasian female with past medical history of hypothyroidism and obesity presented with jaundice. She was treated for acute bacterial rhinosinusitis with Cefprozil 1 week prior. Her only medication was levothyroxine and she denied alcohol use. She had no previous personal or family history of liver disease. Patient had no other stigmata of chronic liver disease on examination. Her initial labs were significant for elevated AST and ALT levels > 10 times the upper limit of normal, total bilirubin of 19.3, creatinine of 1.6 mg/dl, normal TSH level, and INR of 1.7. Acetaminophen levels were negative. The remainder of her work-up revealed (a) normal ceruloplasmin, alpha 1 antitrypsin levels, C282Y and H63D genotypes, (b) negative ANA, ASMA, and anti-LKM titers, (c) negative hepatitis serologies, (d) small shrunken liver and ascites on abdominal ultrasound, (e) negative blood and urine cultures. She underwent a paracentesis with studies demonstrating a SAAG>1.1, total protein <2.5 and normal cell counts. Patient's MELD score on admission was 31 and she developed progressive organ dysfunction with her creatinine, INR and bilirubin reaching peaks of 1.86 mg/dl, 3.3 and 33.2 mg/dl, respectively. She underwent a liver transplant and explant pathology was significant for cirrhosis. A presumed etiology of NAFLD cirrhosis was established. A Roussel Uclaf Causality Assessment Method (RUCAM) score was 8 signifying a probable association. No rechallenge was performed. ACLF is an increasingly recognized entity in the literature with high levels of mortality. 40-50% of cases of ACLF have no identifiable etiology [2]. In this case, a DILI caused by Cefprozil is the likely culprit. This case adds to the growing literature on cephalosporin induced DILI, is the first reported case on Cefprozil to the best of our knowlege, and identifies DILI as a possible etiology of ACLF.