Gastroenterology

Gastroenterology

Volume 130, Issue 7, June 2006, Pages 2031-2038
Gastroenterology

Clinical–liver, pancreas, and biliary tract
Prevalence of the Activating JAK2 Tyrosine Kinase Mutation V617F in the Budd–Chiari Syndrome

https://doi.org/10.1053/j.gastro.2006.04.008Get rights and content

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.

Section snippets

Study Subjects

Sixty patients presenting to King’s College Hospital, London, between 1985 and 2005 were identified from comprehensive databases held within our institution. All patients had objectively confirmed hepatic vein thrombosis. Only patients with “idiopathic BCS” (n = 41) were evaluated; patients with secondary BCS (n = 19) were excluded from the study (Table 1). Fulminant hepatic failure was the presenting feature in 80.5%; the remainder had established chronic liver disease. Racial origin was as

Results

Clinical and laboratory data were retrospectively studied from 41 patients with BCS (female, n = 26; mean age at diagnosis, 35.5 years [standard deviation, 13.3]) presenting to our hospital between 1985 and 2005 (Table 2, Table 3).

Discussion

We have found a high prevalence of JAK2V617F in patients with BCS. Of note, none of the 27 JAK2V617F-positive subjects with BCS were previously known to have MPD. These cases failed to fulfill the accepted diagnostic criteria for MPD8, 9, 10, 11 and therefore represent a group with a “forme fruste” of MPD.

The myeloproliferative disorders are all associated with clonal hematopoiesis with the key abnormality originating within the hemopoietic stem cell. Whereas clonality in the majority of cases

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    Dr Patel and Dr Lea contributed equally to this study.

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