S5832 Acute Liver Injury in Waldenström Macroglobulinemia

Introduction: Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoproliferative disorder defined by IgM monoclonal gammopathy and bone marrow infiltration. While liver involvement is uncommon, WM can rarely manifest with hepatic infiltration or immune-mediated injury. In patients with underlying liver disease, even subtle hepatic involvement may trigger decompensation. We present a case of acute-on-chronic liver failure likely precipitated by treatment-naive WM in a patient with alcohol associated cirrhosis, highlighting the complexity of overlapping hepatic and hematologic disorders. Case Description/Methods: A man with alcohol associated cirrhosis abstinent for 20 years, WM with MYD88 mutation and IgM kappa restriction, chronic kidney disease, and prior nephrectomy for renal mass presented with fatigue, jaundice, and weakness. He was treatment-naive and asymptomatic until outpatient labs showed total bilirubin of 26 mg/dL and international normalized ratio 3.8, prompting admission. Model for End-Stage Liver Disease was 40 and CLIF-C 53. Total protein was 9.3 g/dL, M-spike 4.5 g/dL, lambda light chains 309.4 mg/dL, and kappa/lambda ratio 0.03. Abdominal ultrasound showed patent hepatic vessels. Liver biopsy revealed moderate to severe portal and lobular inflammation with lymphocytes, plasma cells, histiocytes, neutrophils, and focal hepatocyte necrosis. Prussian blue stain was negative. Autoimmune markers, hepatitis panel, iron studies, ceruloplasmin, and Epstein-Barr virus, cytomegalovirus, herpes simplex virus, HIV testing were negative. With renal failure requiring dialysis and ineligibility for transplant due to malignancy, palliative chemotherapy was initiated with rituximab, cyclophosphamide, and dexamethasone. Following initiation of chemotherapy, liver function tests improved. Discussion: In this case, the absence of common risk factors such as immunosuppression or HIV infection obscured the diagnosis. The patient’s systemic findings including cytopenias, renal dysfunction, ascites, and radiographically atypical liver lesions mimicked malignancy or infiltrative disease, leading to extensive workup. This case highlights the importance of considering infectious etiologies, including Bartonella henselae, in patients with multisystem involvement and unexplained hepatic lesions, regardless of immune status. Early recognition is critical, as antimicrobial therapy can lead to complete resolution and prevent unnecessary invasive interventions.