LAUSR

To the Editor: Budd-Chiari syndrome is defined as hepatic venous outflow obstruction in the absence of congestive or restrictive heart disease. Myeloproliferative neoplasms are the leading cause of Budd-Chiari syndrome, diagnosed in 25–50% of such patients. In most patients with Budd-Chiari syndrome and myeloproliferative neoplasms, Janus kinase 2 gene (JAK2) V617F mutation is found in myeloid cells. JAK2 has also been detected in liver endothelial cells of patients with Budd-Chiari syndrome, attributed to a common cell of origin for myeloid and endothelial cells, called hemangioblast. In Budd-Chiari syndrome, JAK2 is associated with poorer prognostic features at presentation and earlier need for hepatic decompression procedures. This observation leads to the hypothesis that JAK2 enhances liver injury and fibrosis induced by hepatic venous outflow obstruction, thus worsening Budd-Chiari syndrome. In order to test this hypothesis, we applied a recently described surgical model of Budd-Chiari syndrome to mice expressing JAK2. JAK2 expression in myeloid cells promotes major vasodilation and hemostasis impairment,