C49-05 Catastrophic Multiorgan Failure From Drug-induced Liver Injury and Metformin-Associated Lactic Acidosis in a Patient Without Baseline Organ Disease

Abstract Introduction Metformin-associated lactic acidosis (MALA) is a rare but potentially fatal complication of metformin therapy, typically seen in patients with renal or hepatic dysfunction. Drug-induced liver injury (DILI) due to metformin itself is exceedingly uncommon, with only isolated case reports. We describe a case of multiorgan failure in a woman without known baseline liver or kidney disease, where hepatic and renal injury synergistically triggered fatal MALA. Case Presentation A 44-year-old woman with chronic myeloid leukemia (CML) in remission on nilotinib and type 2 diabetes mellitus managed with metformin and semaglutide presented with nausea, vomiting, and acute dyspnea. She was found to have severe metabolic acidosis (pH 6.94, bicarbonate 5 mmol/L), lactate 16.7 mmol/L, creatinine 12.1 mg/dL, and elevated liver enzymes and bilirubin. The metformin level was elevated at 37 µg/mL. Continuous venovenous hemodialysis (CVVH) was initiated for presumed MALA with initial improvement. However, by day 8, she developed pericardial tamponade, progressive hepatic failure, and a rising white blood cell (WBC) count peaking at 99,000/µL. Bone marrow biopsy demonstrated a normocellular marrow with no increase in blasts, and no molecular evidence of malignancy, consistent with a reactive process. Liver biopsy showed early cirrhosis, cholestatic hepatitis, and bile infarcts consistent with drug-induced liver injury. Despite maximal support, she developed refractory multiorgan failure and died on hospital day 10. Discussion and Conclusions This case represents an unusually severe and rare presentation of MALA, far exceeding the metabolic derangements typically reported. The reported incidence of MALA is fewer than 10 cases per 100,000 patient-years, usually occurring in those with chronic kidney disease or cirrhosis. Although metformin toxicity and acute kidney injury likely triggered the initial lactic acidosis, the subsequent deterioration despite metabolic correction with CVVH suggests additional contributing factors. Nilotinib, known to cause hepatotoxicity, may have played a role in the development of acute fulminant liver failure. Unlike metformin-associated liver injury, which typically presents as a cholestatic or mixed pattern, nilotinib-induced liver injury more often manifests as asymptomatic transaminase and bilirubin elevations or immune-mediated hepatocellular injury. To our knowledge, this is the only reported case of fatal liver failure in a patient receiving concurrent metformin and nilotinib therapy. This case illustrates a rare and devastating interplay between DILI, MALA, and acute kidney injury in a patient without prior organ dysfunction, underscoring the need for vigilance when combining potentially hepatotoxic and nephrotoxic agents. This abstract is funded by: None