JAK2 (V617F) Mutation Levels and Marrow Fibrosis in Patients Affected by Budd-Chiari Syndrome and Non-Cirrhotic Extra-Hepatic Portal Vein Obstruction.

Abstract

Budd-Chiari syndrome (BCS) and Non-Cirrhotic Extra-Hepatic Portal Vein Obstruction (EHPVO) are two rare vascular diseases of the liver. Inherited and acquired disorders including Myeloproliferative Disorders (MPD) have been frequently reported associated with these diseases, although the large majority of cases is still defined as “idiopathic disease”. The somatic mutation in the tyrosine kinase JAK2 has been described in MPD, specifically in the majority of patients with polycythemia vera (PV), in about half of cases with essential thrombocythemia (ET) and in one third of idiopathic myelofibrosis (IMF), suggesting its pathogenetic role in these diseases. Since the diagnosis of MPD is often difficult in patients with BCS or EHPVO because of spleen enlargement and secondary pancitopenia that can mask erythrocytosis and thrombocytosis, recent observations have included in their diagnostic work-up the analysis of JAK2 mutations. In fact, recently, a high prevalence of JAK2 mutations has been described in splanchnic vein thrombosis. The aim of this study was to evaluate the prevalence and the levels of JAK2 mutation in the patient population affected by BCS and EHPVO followed at our Hepatology Division. The JAK2 mutation was evaluated by allele-specific real-time TaqMan polymerase chain reaction. We enrolled in this study 18 patients (median age: 38 ± 9.8 years) affected by BCS (7 patients), EHPVO (10 patients), or both (1 patient). In 9 of them the JAK2 mutation was absent, while it was demonstrated in the remaining cases. Among these, an heterozygous deletion (JAK2 mutation ranging between 2.7% and 48%) was detected in 5 and an homozygous deletion (55.7%–88%) in 4. A diagnosis of PV was made in 2 patients with JAK2 heterozygous deletion affected by BCS and EHPVO. The 3 IMF were all characterized by homozygous deletions: 1 had BCS and 2 EHPVO. In the remaining 3 patients, in the absence of other diagnostic criteria, only the bone marrow biopsy revealed the presence of initial marrow fibrosis: grade 0–1 (2 patients both affected by EHPVO with heterozygous and homozygous deletion) and grade 1 (in a heterozygous patient affected by EHPVO). In summary, the JAK2 mutation was demonstrated in half of the cases with vascular liver diseases, regardless of the JAK mutation levels. The marrow fibrosis was, in these cases, frequently associated with both BCS and EHPVO, suggesting a common potential pathogenetic role in these vascular diseases of the liver.