Prevalence of the Activating JAK2 Tyrosine Kinase Mutation V617F in the Budd–Chiari Syndrome

Background & Aims: Budd–Chiari Syndrome (BCS) results from obstruction to hepatic venous outflow, with myeloproliferative disorder (MPD) accounting for up to 40% of cases. A number of BCS cases labelled as “idiopathic” do not fulfill the diagnostic criteria for MPD but have features suggestive of a latent form based on hyperplastic bone marrow and erythroid progenitor cell culture; these cases may subsequently develop overt MPD. A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of use in the characterization of latent MPD in BCS. Methods: We performed allele-specific polymerase chain reaction to screen for JAK2V617F in subjects with BCS (n = 41) and polycythemia vera (PV) (n = 20) and in hematologically normal controls (n = 27). Results: AK2V617F was detected in 24 of 41 (58.5%) subjects with BCS, 19 of 20 PV controls, and 0 of 27 hematologically normal controls. Mean hemoglobin concentration and hematocrit were significantly higher in patients with JAK2V617F. Bone marrow was hyperplastic in 16 of 41 subjects (12/16 JAK2V617F positive). Nine of 33 (27.3%) showed endogenous erythroid colony formation (7/9 JAK2V617F positive). Eleven of 41 subjects developed overt MPD (8/11 essential thrombocythemia, 3/11 PV) after the diagnosis of BCS (median, 49 months; range, 8–87 months), and in 90.9% of these JAK2V617F was detected. Conclusions: JAK2V617F occurs in a high proportion of patients with BCS. Latent MPD was missed in a substantial number of our subjects by using standard techniques. Such cases should be screened for JAK2V617F and carefully observed for the subsequent development of overt MPD.

Abbreviations used in this paper: BCS, Budd–Chiari Syndrome, BM, bone marrow, EEC, endogenous erythroid colony, ET, essential thrombocythemia, MPD, myeloproliferative disorder, OLT, orthotopic liver transplantation, PV, polycythemia vera, WHO, World Health Organization