Acute Acalculous Cholecystitis Mimicry: Symptomatic Hepatic Infiltration From Chronic Lymphocytic Leukemia Presenting as Cholestatic Liver Injury

Abstract Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States. CLL can infiltrate the liver parenchyma or sinusoids, rarely causing symptomatic hepatic outflow obstruction or acute liver failure, making such complications difficult to recognize. We describe a patient with symptomatic, nonobstructive cholestatic liver injury due to CLL infiltration. A 53-year-old man with CLL diagnosed 4 years prior (Rai stage 0 at diagnosis), managed with observation, presented with 10 days of fever, nausea, vomiting, and diarrhea. Examination was significant for fever (39°C) and right upper quadrant tenderness with no hepatomegaly appreciated on palpation. Laboratory testing demonstrated leukocytosis and a cholestatic-predominant liver injury. Imaging demonstrated gallbladder wall thickening, splenomegaly with diffuse lymphadenopathy, a normal-appearing liver, and no biliary obstruction. Empiric antibiotics did not result in clinical improvement. The hospital course was complicated by worsening leukocytosis and elevation in inflammatory markers. Liver biopsy demonstrated portal and sinusoidal infiltration by small mature lymphocytes, consistent with CLL infiltration. The patient was discharged on hospital day 8 after biochemical and clinical improvement with pulse-dose dexamethasone. Allopurinol was initiated for tumor lysis prophylaxis. Combination therapy with obinutuzumab and venetoclax was initiated for Rai stage III CLL. Symptomatic manifestations of CLL-induced hepatic infiltration are extremely rare. In patients with cholestatic-predominant liver injury and negative biliary imaging, particularly with known CLL or unexplained splenomegaly/adenopathy, malignant hepatic infiltration should be considered early, and liver biopsy can be diagnostic and expedite definitive therapy.