Abstract and Introduction
Abstract
Background It is important to evaluate whether screening for JAK2V617F mutation should be routinely performed in patients with Budd–Chiari syndrome (BCS) and portal venous system thrombosis (PVST). However, the prevalence of JAK2V617F mutation in such patients is substantially varied, and its association with development of myeloproliferative disorders (MPD) is deficiently identified.
Aims To estimate the prevalence of JAK2V617F mutation and to explore the significance of screening for JAK2V617F mutation in these patients.
Methods All observational studies regarding the prevalence of JAK2V617F mutation in patients with BCS and PVST were identified via PubMed and MEDLINE databases. Primary items were the proportions of JAK2V617F mutation and MPD.
Results Twenty-three studies fulfilled the inclusion criteria. Regardless of underlying aetiological factors, the pooled prevalence of JAK2V617F mutation was 37% and 24% in patients with BCS and PVST respectively. After pre-existing MPD was excluded, the pooled prevalence was decreased to 26% and 19%. Heterogeneity among studies was significant for the prevalence of JAK2V617F mutation. Compared with healthy subjects and patients with thrombosis in other sites, the prevalence of JAKV617F mutation was significantly higher in patients with BCS and PVST. The prevalence of MPD was significantly higher in patients with JAK2V617F mutation than those without.
Conclusions JAK2V617F mutation is frequently found in patients with BCS and PVST, but there is a huge variation of prevalence among the included studies. Additionally, it is more specific to thrombosis in splanchnic areas and strongly associated with the development of MPD in these patients. Further studies are needed to evaluate whether the screening test should be widely performed in Asian countries and cirrhotic patients.
Introduction
Splanchnic vein thrombosis (SVT) includes Budd–Chiari syndrome (BCS) and extrahepatic portal venous system thrombosis (PVST). The first one is characterised by hepatic outflow tract obstruction in the absence of cardiac and pericardial diseases. The latter one refers to thrombosis within the extrahepatic portal vein, mesenteric vein and splenic vein. The most important systemic aetiological factor for SVT is myeloproliferative disorders (MPD). However, in the setting of SVT, it is difficult to make a diagnosis of overt MPD by using non-invasive conventional criteria, due to the following three points that harbour the elevation of peripheral blood cell counts: (i) extrahepatic portal hypertension and its secondary splenomegaly and hypersplenism; (ii) iron deficiency; and (iii) haemodilution. Bone marrow biopsy is regarded as a major diagnostic tool for MPD. But the patients with SVT are often diagnosed with coagulation disorders and receive permanent anticoagulation therapy, so that the routine use of the invasive procedure appears to be limited in these patients due to potential bleeding risks.
JAK2V617F mutation is found in approximately 90% of patients with polycythaemia vera and half of patients with essential thrombocythaemia and idiopathic myelofibrosis. Given a high prevalence of MPD in patients with SVT, it seems that JAK2V617F mutation detection should be incorporated into routine thrombophilic screening work-up. However, the prevalence of JAK2V617F mutation is substantially varied in different studies, mainly owing to the fact that each study uses its own eligibility criteria and sample size is small. Additionally, the principle purpose of JAK2V617F mutation detection in clinical practice is to assess the possibility of the potential development of MPD in patients with SVT. Therefore, it is more informative for clinicians to observe the prevalence of JAK2V617F mutation in SVT patients without a previous diagnosis of MPD.
We have conducted a systematic review and meta-analysis to evaluate whether screening for JAK2V617F mutation should be routinely performed in patients with SVT by resolving the following three questions: (i) What is the prevalence of JAK2V617F mutation in patients with SVT, especially in those without pre-existing MPD at the diagnosis of SVT? (ii) Is JAK2V617F mutation more specific to the patients with SVT than those with thrombosis outside the splanchnic vein and healthy subjects? (iii) Is there a strong association between JAK2V617F mutation and development of MPD in patients with SVT? This work is performed using the guidelines for the reporting of meta-analysis of observational studies, which were published by the Meta-analysis of Observational Studies in Epidemiology Group in 2000.