A 64-year-old male with a 10-year history of asymptomatic JAK-2-positive PMF under observation presented with progressive pruritus and jaundice for 3 days. Labs revealed ALT 49 IU/L, AST 35 IU/L, ALP 378 IU/L, total bilirubin (TB) 17 mg/dL, and direct bilirubin 10 mg/dL. LDH was 173 U/L, and the haptoglobin level was normal. Complete blood count with differential showed WBC 4.4 x 103/uL (85% neutrophils, 8% lymphocytes, and 4% monocytes), hemoglobin 7.4 g/dL, and platelets 103 x 109/L. Lipid panel showed total cholesterol 229 mg/dL, triglyceride 171 mg/dL, HDL 5 mg/dL, and LDL 193 mg/dL. Anti-mitochondrial antibody was negative with titer <1 : 20. Workup for metabolic, viral, autoimmune, alcoholic, and drug-induced liver disease otherwise was unrevealing. The patient denied the use of any drugs, including herbal supplements. CT scan showed hepatomegaly without biliary ductal dilatation, along with marked splenomegaly with a spleen size of 27 cm. MRCP failed to demonstrate findings of an obstructive etiology. Therefore, EUS and ERCP were performed which were also unremarkable. Given worsening hyperbilirubinemia, a liver biopsy was subsequently pursued which was suggestive of a nonspecific cholestatic liver injury (Figures 1-3). TB continued to increase to 25 mg/dL, and a repeat ERCP was performed which was unremarkable. During the ERCP, a sphincterotomy was performed with biliary sweep which was unremarkable with cytology showing benign reactive epithelial cells. Liver biopsy was also repeated which showed similar findings as prior. Throughout his course, the patient also did not have any fevers, right upper quadrant pain, or leukocytosis to suggest underlying infection including acute cholangitis. Bone marrow biopsy performed showed hypercellular (90%) with 3+ reticulin fibrosis and no increased blasts, consistent with underlying primary myelofibrosis. TB continued to rise to 29 mg/dL, and given negative extensive workup otherwise, the decision was made to start empiric treatment for possible PMF-related disease. Dynamic International Prognostic Scoring System (DIPSS) score was 2, correlating with intermediate risk. Ruxolitinib was initiated with significant improvement of TB to 18 mg/dL. 3 weeks after initiation, ruxolitinib had to be temporarily held due to adverse effects of bone marrow suppression, and TB subsequently increased to 35 mg/dL over the next 5 weeks. Ruxolitinib was then resumed at a lower dose with improvement again of TB to 17 mg/dL (Figure 4). The patient's course was unfortunately complicated by renal failure secondary to biopsy-confirmed bile-acid nephropathy, ascites, functional decline, and eventually was transitioned to hospice.