Budd-Chiari syndrome (ORPHA:131)
A rare vascular liver disease characterized by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava.
Epidemiology
Prevalence of Budd-Chiari syndrome (BCS) remains largely unknown but estimates range between 1/50,000 and 1/100,000.
Clinical description
The obstruction leads to hepatic congestion and ischemic necrosis. Severity depends on the speed of onset and extent of the obstruction. Obstructions are generally caused by thrombosis (primary BCS). With time, thrombi reorganize to form a fibrous tissue that leads either to localized stenosis of the thrombotic vein or to diffuse obliteration resulting in its transformation into fibrous cords. Localized stenoses may present as the appearance of a membrane-like structure. Secondary BCS results from tumor invasion into the lumen or compression of the vein by an expansive lesion. BCS presentation and manifestations are extremely diverse, so that the diagnosis must be considered in any patient with acute, acute-on-chronic or chronic liver disease. The principal manifestations of BCS are ascites (which is often massive and intractable) leading to undernutrition and renal insufficiency, gastrointestinal hemorrhage due to portal hypertension, and hepatic insufficiency resulting in encephalopathy and severe infections. However, asymptomatic forms have also been reported.
Etiology
Primary BCS is associated with a combination of factors that lead to a susceptibility for venous thrombosis: primary myeloproliferative neoplasms (present in 50% of cases and manifesting as a 'forme fruste' or atypical forms of the disease, but identified through detection of the JAK2 V617F mutation, CALR mutations or others), Factor V Leiden thrombophilia, protein C deficiency, antiphospholipid syndrome, Behcet disease, paroxysmal nocturnal hemoglobinuria, use of estrogen-progesterone oral contraceptives and systemic inflammatory diseases.
Diagnostic methods
Diagnosis can usually be established by non-invasive means through imaging of the hepatic veins and the inferior vena cava (Doppler ultrasound, tomodensitometry and MRI) but requires a radiologist with sufficient experience and with an awareness of the potential diagnosis. Liver biopsy should not be performed to diagnose BCS when vascular imaging demonstrates obstruction of the hepatic venous outflow tract. Hepatic venography or cavography, and liver puncture biopsy are necessary only when BCS of the small hepatic veins is not seen on imaging.
Differential diagnosis
Differential diagnoses include hepatic veno-occlusive disease / sinusoidal obstruction syndrome (VOD/SOS), cardiac failure, decompensated chronic liver disease, and tumoral invasion of the liver.
Management and treatment
Treatment approaches include correction of the factors leading to an increased risk of thrombosis, long-term anticoagulant therapy, recanalization of the obstructed veins by interventional radiology, TIPS (transjugular intrahepatic portosystemic shunt) and liver transplantation in case of failure of other treatment methods.
Prognosis
The natural course of the disease is very severe (less than 10% of patients survive for more than 3 years without treatment). At present, when the diagnosis is made quickly and treatment is initiated rapidly, the survival rate is 90% at 5 years. The long-term prognosis depends on the associated risk factors for thrombosis.

                            Last update: 
                            November 2021


                            - Expert reviewer(s): 
                            Dr Aurélie PLESSIER | RARE-LIVER*


                                * European Reference Network