Cytarabine is one of the chemotherapy agents used to treat myelodysplastic syndrome, and its use can lead to isolated direct hyperbilirubinemia. 54 year old man with MDS s/p AI induction and HIDAC cycle 1 day 10 presented with fever of 102, diffuse abdominal pain, and diarrhea. Physical exam revealed jaundice and mild LUQ and RUQ abdominal tenderness. Labs revealed neutropenia, total bilirubin 7.2, direct bilirubin 5.4, AST 19, ALT 41, alk phos 70. Abdominal US did not show cholelithiasis. Abdominal Doppler US showed patent hepatosplenic vasculature. CT A/P showed diffuse circumferential thickening of multiple mid to distal small bowel loops which may be secondary to infectious enteritis. The patient's bilirubin continued to rise, peaking 6 days after admission at 15.7 and transaminases remained normal to mildly elevated (Figure 1). Other labs including ANA, anti-smooth muscle antibody, mitochondrial antibody, hepatitis A, B, and C, cerulopasmin, immunoglobulins, anti-SLA, and alpha-1 anti-trypsin were negative. Liver biopsy showed benign hepatic parenchyma. Patient was treated with Meropenem for neutropenic enterocolitis. After neutropenia improved, bilirubin trended down (Figure 2), and patient was discharged on day 16. Several case reports have described severe isolated hyperbilirubinemia following the use of high dose cytarabine in the treatment of hematologic malignancies. Aside from isolated direct hyperbilirubinemia, patients present with neutropenia, and can have fever, abdominal pain, and diarrhea during the second week of therapy. Concomitantly, they are diagnosed with neutropenic entercolitis. The mechanism of action for the isolated hyperbilirubinemia is not known but is likely similar to the pathogenesis of neutropenic enterocolitis, where cytarabine has cytotoxic effects on the gastrointestinal mucosa leading to hyperpermeability of the mucosal barrier. Cytarabine may have a similar effect on the gallbladder mucosa, leading to bile leak age and isolated hyperbilirubinemia. Despite the use of percutaneous drainage, the hyperbilirubinemia does not resolve as expected and improves after neutropenic recovery, suggesting the mechanism is not only secondary to cholestasis but related to the integrity of gallbladder mucosa. This case highlights another rare presentation of isolated hyperbilirubinemia with the use of HIDAC and illustrates the timeline of hyperbilirubenima after intiation of HIDAC and its resolution after neutropenia recovery.1354_A.tif Figure 1: Liver enzyme course since treatment with high dose cytarabine. Left Y axis for alkaline phosphatase, ALT, and AST. Right Y axis for total bilirubin and direct bilirubin.1354_B.tif Figure 2: Trend of white blood cells, total bilirubin, and direct bilirubin since treatment with high dose cytarabine. Left Y axis for WBC, and right Y axis for total and direct bilirubin.