A pivotal discovery related to MPS involves a somatic mutation (V617F) within the Janus tyrosine kinsase-2 (JAK2) gene in myeloid cells. This mutation has been detected in 37% to 45% of patients with primary BCS and approximately 80% of BCS patients with an MPS.3
In the presence of BCS, the peripheral blood cell count tends to remain within normal limits in patients with an MPS, which curtails recognition of an underlying syndrome. Hypersplenism, hemodilution, occult gastrointestinal bleeding, and iron deficiency all mask peripheral blood abnormalities.
The proposed workup for investigating underlying risk factors for individuals with BCS should include testing for V617F JAK2 in peripheral blood granulocytes. If no mutation is detected, bone marrow biopsy should be performed to search for clusters of dystrophic megakaryocytes indicative of an MPS.3
In a study of 163 patients with newly diagnosed BCS, most had identifiable risk factors. An MPS, the most frequent causative factor, was found in 50 (49%) of the 103 patients who underwent bone marrow biopsy, red cell mass measurement, and colony cultures. The V617F JAK2 mutation was identified in 35 (25%) of 121 tested patients. Twenty-eight of the 35 individuals with the mutation had features of an MPS on bone marrow biopsy.8
History and Physical Findings
Because the presentation of BCS is highly variable, providers should consider it in the differential diagnosis of patients presenting with acute or chronic liver failure. Common BCS symptoms include fever, abdominal tenderness, abdominal distension, hepatosplenomegaly, lower extremity edema, and ascites.9 Jaundice, gastrointestinal bleeding, and hepatic encephalopathy may be evident but are less common presenting symptoms.9
More than 60% of patients with BCS will present with sudden-onset abdominal pain, hepatomegaly, and ascites. Providers also should recognize features of nephrotic syndrome, such as proteinuria, edema, and hypoalbuminemia.2 An absence of symptoms at the time of diagnosis, which occurs in as many as 20% of patients with BCS, correlates with large hepatic venous collaterals.10
Acute, subacute, and chronic forms of BCS are categorized by the duration and severity of acute fulminant liver failure. Fulminant BCS is rare; approximately 5% of patients will present with acute liver failure demonstrated by elevated transaminase levels, jaundice, hepatic encephalopathy, and an international normalized ratio (INR) >1.5.2
Approximately 20% of patients with BCS present with an acute form, in which accelerated development of manifestations occurs rapidly over the course of a few weeks.11 Such patients present with severe right upper quadrant pain, hepatomegaly, and eventually jaundice and ascites.11
Most causes of BCS are subacute and chronic in nature.2 In subacute or chronic BCS, patients often are symptomatic; the obstruction is gradual and generally discovered incidentally, such as when imaging studies or liver function tests are ordered for unrelated reasons. In subacute BCS, symptoms develop slowly over the course of 3 to 6 months, and patients may experience vague abdominal or right upper quadrant pain reflective of increasing portal vein pressure. In chronic BCS, symptoms of chronic liver disease, such as spider angiomas, palmar erythema, ascites, and esophageal varices, are delayed until the patient develops cirrhosis.