Guideline sources The following summarized guidelines for the evaluation and management of Budd-Chiari syndrome (BCS) are prepared by our editorial team based on guidelines from the American Society of Hematology (ASH 2023), the American Association for the Study of Liver Diseases (AASLD 2021), the American College of Gastroenterology (ACG 2020), the European Association for the Study of the Liver (EASL 2016), the Italian Association for the Study of the Liver (AISF 2016), and the Baveno VI Consensus Workshop (Baveno VI 2015). 1 2 3 4 5 6 7 8 8 9 Definition BCS is a liver disease that results from hepatic venous outflow obstruction characterized by a triad of abdominal discomfort, hepatomegaly, and ascites. 7 Epidemiology Etiologies of BCS can be broadly classified into thrombotic causes (primary myeloproliferative diseases, underlying thrombophilia) and non-thrombotic causes (compression due to tumors of adjacent organs, polycystic kidney disease, parasitic liver disease). 8 Disease course https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 1/7 6/29/23, 3:21 AM Budd-Chiari syndrome Pathway Disease course Obstruction of hepatic veins increases sinusoidal pressure and reduces sinusoidal blood blow, leading to clinical manifestations of acute abdominal pain, ascites, and hepatomegaly, or chronic symptoms of long-standing portal hypertension. Disease progression may result in fibrosis and fulminant hepatic failure. 8 Prognosis and risk of recurrence 1-year and 5-year mortality rate of treated BCS is 6% and 13%, respectively. 9 Pathway Budd-Chiari syndrome Diagnosis and management Guidelines 1. Screening and diagnosis Diagnosis: As per AASLD 2021 guidelines, suspect the diagnosis of BCS in any patient with liver disease (recent or chronic) of unknown etiology, especially with a higher suspicion in a patient with a recognized prothrombotic disorder. E As per EASL 2016 guidelines, assess the probability of BCS in any symptomatic or asymptomatic patient with acute or chronic liver disease. A As per Baveno VI 2015 guidelines, diagnose BCS by the demonstration of an obstruction of the venous lumen, or by the presence of hepatic vein collaterals. B 2. Diagnostic investigations Diagnostic imaging: As per AASLD 2021 guidelines: Obtain Doppler ultrasound, performed by an experienced operator, as the first-line imaging modality for BCS. E Consider obtaining CT or MRI for diagnostic confirmation and interventional planning. E As per ACG 2020 guidelines: Obtain Doppler ultrasound as the initial diagnostic test for evaluation for BCS. B Obtain contrast-enhanced CT or MRI to assess thrombus extension, rule out tumor thrombus, determine response to anticoagulation therapy, evaluate indeterminate hepatic nodules, and https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 2/7 6/29/23, 3:21 AM Budd-Chiari syndrome Pathway whenever there is high clinical suspicion of BCS despite negative or inconclusive Doppler ultrasound results. B As per EASL 2016 guidelines, obtain Doppler ultrasound as the first line of investigation for BCS, and use MRI or CT for diagnostic confirmation. A Prothrombotic workup: As per AASLD 2021 guidelines: Obtain a full thrombophilia workup in patients with BCS at the time of diagnosis. Obtain testing for additional factors when one causal factor is identified. E Consult with a hematologist in the evaluation of patients with BCS. E As per EASL 2016 guidelines, evaluate patients with BCS for underlying local and systemic prothrombotic factors, including intra-abdominal inflammatory conditions and abdominal malignancies, inherited and acquired thrombophilias, myeloproliferative neoplasms, paroxysmal nocturnal Hgburia and autoimmune disorders. Do not stop evaluating for additional risk factors if one risk factor is identified. A Show 3 more 3. Medical management General principles: As per AASLD 2021 guidelines, offer a progressive step-up therapeutic strategy according to the clinical response from less to more invasive therapies in patients with BCS. E As per ACG 2020 guidelines, offer stepwise management from least to most invasive therapies in patients with BCS. B As per EASL 2016 guidelines, treat any underlying prothrombotic condition appropriately. B As per Baveno VI 2015 guidelines, offer a stepwise approach for the management of patients with BCS, including anticoagulation, angioplasty/thrombolysis, TIPS and orthotopic liver transplantation at experienced centers. B Anticoagulant therapy, initiation: As per AASLD 2021 guidelines, initiate therapeutic anticoagulation in all patients with BCS, even in the absence of a recognized prothrombotic disorder. E As per ACG 2020 guidelines, initiate systemic anticoagulation as the initial treatment of choice in patients with BCS. B As per EASL 2016 guidelines: Initiate anticoagulant therapy in patients with BCS in the absence of major contraindications. A Recognize that portal hypertension complications, when adequately treated, are not a contraindication for anticoagulation. B As per Baveno VI 2015 guidelines, initiate long-term anticoagulation in all patients with BCS, although insufficient evidence to support its use in patients without identified risk factors. B https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 3/7 6/29/23, 3:21 AM Budd-Chiari syndrome Pathway Anticoagulant therapy, duration: As per ASH 2023 guidelines: Consider obtaining thrombophilia testing to guide anticoagulant treatment duration after primary treatment in patients with splanchnic venous thrombosis in a setting where anticoagulation would be discontinued. Consider continuing anticoagulation indefinitely in patients with thrombophilia. C Avoid obtaining thrombophilia testing to guide anticoagulant treatment duration after primary treatment in patients with splanchnic venous thrombosis in a setting where anticoagulation would be continued indefinitely. D As per EASL 2016 guidelines, continue anticoagulant therapy indefinitely in patients with BCS and an underlying myeloproliferative neoplasm. B 4. Therapeutic procedures Hepatic vein or inferior vena cava angioplasty: As per ACG 2020 guidelines, perform angioplasty in patients with BCS if medical therapy fails, as determined by worsening liver and/or renal function, ascites, or hepatic encephalopathy. B As per EASL 2016 guidelines, perform angioplasty/stenting as the first-line decompressive procedure in patients with short hepatic vein stenosis or IVC stenosis. A As per Baveno VI 2015 guidelines, evaluate for and treat stenoses amenable to percutaneous angioplasty/stenting (short-length stenoses). B Transjugular intrahepatic portosystemic shunt: As per AASLD 2021 guidelines: Perform TIPS or DIPS using PTFE-covered stents in patients with BCS when medical therapy or angioplasty fail or are not feasible. E Consider performing TIPS/DIPS in patients with ALF while waiting for transplant because it may improve liver function and potentially avoid the need for transplantation. E As per ACG 2020 guidelines, perform TIPSing in patients with BCS if medical therapy fails, as determined by worsening liver and/or renal function, ascites, or hepatic encephalopathy. B As per EASL 2016 guidelines: Perform a portal derivative technique in patients not responding to initial therapy or angioplasty/stenting. A Perform TIPS implantation, unless contraindicated, as the first-line portal derivative technique. A As per Baveno VI 2015 guidelines: Attempt performing TIPS by experts when angioplasty/stenting is not feasible, and when medical therapy fails. B Consider obtaining BCS-TIPS Prognostic Index score for outcome prediction in patients with BCS undergoing TIPS. Recognize that patients with high ( 7) BCS-TIPS Prognostic Index https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 4/7 6/29/23, 3:21 AM Budd-Chiari syndrome Pathway score are likely to have poor outcome following TIPS. C 5. Surgical interventions Surgical portosystemic shunt: As per AASLD 2021 guidelines: Reserve liver transplantation for patients with BCS when medical and vascular interventional approaches fail. E Consider performing liver transplantation as the first step in patients with ALF. Consider performing TIPS/DIPS in patients with ALF while waiting for transplant because it may improve liver function and potentially avoid the need for transplantation. E As per EASL 2016 guidelines, discuss surgical shunting when TIPS is not feasible or fails for patients not responding to initial therapy, or not responding to angioplasty/stenting with portal derivative techniques. B Liver transplantation: As per ACG 2020 guidelines, reserve liver transplantation for patients with TIPS failure and BCS presenting as fulminant liver failure. B As per EASL 2016 guidelines, propose liver transplantation as a salvage treatment for appropriate candidates in whom derivative techniques have failed. A As per Baveno VI 2015 guidelines: Consider performing liver transplantation in patients with BCS and manifestations refractory to medical and interventional approaches. C Consider performing orthotopic liver transplantation in patients with BCS and a high ( 7) BCS-TIPS Prognostic Index score. C 6. Specific circumstances Pregnant patients: recognize that pregnancy may precipitate BCS, and the clinical presentation is often fulminant. Offer the same treatment of BCS during pregnancy as in non-pregnant patients, except for the contraindication of vitamin K antagonists. B Show 3 more Patients with portal hypertension: treat portal hypertension in patients with BCS since it is the major risk factor for bleeding, while excess anticoagulation plays a secondary role. B Show 2 more 7. Follow-up and surveillance Indications for referral: https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 5/7 6/29/23, 3:21 AM Budd-Chiari syndrome Pathway As per AASLD 2021 guidelines, refer patients with BCS to tertiary care centers with expertise in this disorder. E As per ACG 2020 guidelines, consider referring patients with BCS to centers of expertise in diagnosis of HCC for HCC surveillance, because its diagnosis is challenging. C Surveillance for hepatocellular carcinoma: As per AASLD 2021 guidelines: Obtain surveillance for HCC in patients with chronic BCS as in patients with cirrhosis, with ultrasound every 6 months with or without AFP determination. E Do not rely on imaging criteria alone, rather perform histological confirmation for the diagnosis of HCC in patients with BCS, because of the perturbed vascularity of the liver. D As per ACG 2020 guidelines, consider obtaining surveillance for HCC with abdominal ultrasound and serum AFP levels every 6 months in patients with chronic BCS. C Clinical findings Symptoms Past medical history Abdominal pain Age peak 20-40 years Fatigue IBD RUQ pain Liver cirrhosis Vomiting Myeloproliferative disease Portal hypertension Past obstetric history Vascular exam Pregnancy Leg edema Neurological exam Abdominal exam Encephalopathy Ascites Integument exam Splenomegaly Jaundice Lab findings Hematological findings High serum protein concentrations (>2 g/dL) Coagulopathy Serum ascites-albumin gradient < 1.1 Polycythemia blood platelet count serum transaminases References 1. Patrick G Northup, Juan Carlos Garcia-Pagan, Guadalupe Garcia-Tsao et al. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 6/7 6/29/23, 3:21 AM Budd-Chiari syndrome Pathway by the American Association for the Study of Liver Diseases. Hepatology. 2021 Jan;73 1 366 413. Open 2. Douglas A Simonetto, Ashwani K Singal, Guadalupe Garcia-Tsao et al. ACG Clinical Guideline: Disorders of the Hepatic and Mesenteric Circulation. Am J Gastroenterol. 2020 Jan;115 1 18 40. Open 3. de Franchis R, Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015 Sep;63 3 743 52. Open 4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatol. 2016 Jan;64 1 179 202. Open 5. Saskia Middeldorp, Robby Nieuwlaat, Lisa Baumann Kreuziger et al. American Society of Hematology 2023 Guidelines for Management of Venous Thromboembolism: Thrombophilia Testing. Blood Adv. 2023 May 17;bloodadvances.2023010177. Open 6. Italian Association for the Study of the Liver AISF , Italian Association for the Study of the Liver AISF. AISF position paper on liver disease and pregnancy. Dig Liver Dis. 2016 Feb;48 2 120 37. Open 7. M A Fox, J A Fox, Mervyn H Davies. Budd-Chiari syndrome a review of the diagnosis and management. Acute Med. 2011;10 1 5 9. Open 8. Musa Aydinli, Yusuf Bayraktar. Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. World J Gastroenterol. 2007 May 21;13 19 2693 6. Open 9. D C Valla. Prognosis in Budd Chiari syndrome after re-establishing hepatic venous drainage. Gut. 2006 Jun;55 6 761 3. Open 10. M A Fox, J A Fox, Mervyn H Davies. Budd-Chiari syndrome a review of the diagnosis and management. Acute Med. 2011;10 1 5 9.2011;10 1 5 9. Open 11. Musa Aydinli, Yusuf Bayraktar. Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. World J Gastroenterol. 2007 May 21;13 19 2693 6.2007 May 21;13 19 2693 6. Open 12. D C Valla. Prognosis in Budd Chiari syndrome after re-establishing hepatic venous drainage. Gut. 2006 Jun;55 6 761 3.2006 Jun;55 6 761 3. Open 13. Monika Sarkar, Carla W Brady, Jaquelyn Fleckenstein et al. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Jan;73 1 318 365. Open https://web.pathway.md/diseases/recZp9vpZB3eFQ2VE 7/7