What is the treatment approach for Budd-Chiari syndrome?

Treatment of Budd-Chiari Syndrome

All patients with Budd-Chiari syndrome require immediate lifelong anticoagulation followed by a stepwise therapeutic algorithm: medical management → angioplasty/stenting for focal stenoses → TIPS for refractory cases → liver transplantation as salvage therapy. 1

Immediate Initial Management

Anticoagulation (First-Line for All Patients)

• Initiate anticoagulation as soon as possible and continue indefinitely to reduce the risk of clot extension and new thrombotic episodes 2, 1
• Start with low molecular weight heparin (LMWH) for at least 5-7 days, then transition to oral vitamin K antagonists (warfarin) targeting INR 2-3 1
• Overlap VKA with parenteral anticoagulation for at least 5 days and continue parenteral therapy until INR has been 2.0-3.0 for two consecutive days 1
• Portal hypertension complications (varices and ascites), when adequately treated, are NOT contraindications to anticoagulation 1
• Bleeding complications have decreased from 50% to 17% with better procedural management and adequate portal hypertension prophylaxis 1

Treatment of Underlying Prothrombotic Conditions

• Complete thrombophilia screening is mandatory before initiating treatment, including protein S, protein C, antithrombin levels, Factor V Leiden mutation, prothrombin G20210A gene variant, antiphospholipid antibodies, JAK2V617F mutation, and calreticulin mutation screening 1
• For myeloproliferative neoplasms: use hydroxyurea or alpha interferon to normalize peripheral blood cell counts 1
• For polycythemia vera: maintain hematocrit <45% 1
• For paroxysmal nocturnal hemoglobinuria: consider long-term eculizumab 1

Management of Portal Hypertension Complications

• Manage ascites and varices following the same treatment recommendations as for cirrhosis 1
• Implement primary prophylaxis with non-selective beta-blockers or endoscopic variceal ligation for high-risk varices 3, 1
• TIPS should be considered for recurrent variceal bleeding despite adequate endoscopic and medical treatment 3

Stepwise Interventional Algorithm

Step 1: Angioplasty/Stenting (For Focal Stenoses)

• Angioplasty with stenting is the first-line decompressive procedure for patients with short hepatic vein stenosis or IVC stenosis 1
• Indicated for patients with partial or segmental stenoses, present in 60% of patients with IVC obstruction and 25-30% of those with hepatic vein obstruction 1
• Most effective in patients with short, focal stenoses where physiological drainage of portal and sinusoidal blood can be re-established 1
• Stenting reduces re-stenosis rates compared to angioplasty alone 1
• Caution: Misplacement of stents may compromise subsequent TIPS performance or liver transplantation 1

Step 2: TIPS (For Refractory Cases)

• TIPS using PTFE-covered stents exclusively is the definitive treatment of choice for patients who fail medical therapy or when angioplasty/stenting is ineffective or technically impossible 1
• Specific indications include: failure to respond to anticoagulation therapy, fulminant Budd-Chiari syndrome, recurrent variceal bleeding despite adequate endoscopic and medical treatment 1
• TIPS achieves symptom resolution exceeding 70% with 5-year survival rates exceeding 70% 1
• Use PTFE-covered stents exclusively, as they improve primary patency compared to bare stents 1
• Risk of hepatic encephalopathy after TIPS is approximately 15% 1
• Direct intra-hepatic porto-caval shunt (DIPS) can be performed when all hepatic veins are occluded, with similar clinical outcomes to classical TIPS 1
• TIPS placement in BCS requires special training, as in more than 45% of cases a transcaval approach (direct puncture from the intrahepatic IVC) may be required due to complete thrombosis of the hepatic veins 2

Step 3: Surgical Shunting (When TIPS Not Feasible)

• Surgical shunting (mesocaval shunt with PTFE or autologous jugular vein) should be discussed when TIPS is not feasible or fails 1
• However, surgical shunts have not demonstrated independent survival advantage compared to TIPS and are associated with higher morbidity and mortality rates 2
• Surgical shunts have high rates of dysfunction/thrombosis 2

Step 4: Liver Transplantation (Salvage Therapy)

• Liver transplantation is reserved for patients who fail all other therapeutic options, particularly those with BCS-TIPS score >7, which consistently predicts poor outcomes 1
• Best results achieved in patients with thrombosis limited to the hepatic veins and when the underlying cause can be corrected by liver replacement 1
• OLT-free survival with TIPS at 1 and 5 years is 88% and 78%, respectively 2
• Survival after OLT is similar to that obtained in patients initially treated with TIPS 2
• For patients presenting with fulminant hepatic failure: refer immediately to a transplant center with consideration of urgent TIPS placement and transplantation as soon as possible 1
• Previous TIPS placement does not make subsequent OLT more difficult 2
• BCS recurrence after OLT has markedly dropped since initiation of early anticoagulation treatment after OLT and its lifelong maintenance 2

Monitoring and Follow-Up

• Doppler ultrasound should be performed early after TIPS placement and then every 6 months to detect thrombosis or TIPS dysfunction 1
• Regular monitoring of anticoagulation therapy is essential to maintain target INR 2-3 1
• Check INR at least weekly during initiation phase; once stable, INR testing can be extended to monthly intervals 1
• Screening for hepatocellular carcinoma is recommended as patients with BCS may develop hypervascular liver nodules 1

Specialized Center Management

All patients with Budd-Chiari syndrome must be managed in specialized centers with expertise in hepatology, interventional radiology, and formal links to liver transplant centers 1

Special Populations

Pregnancy

• Pregnancy in patients with BCS has excellent maternal outcome provided patients have well-controlled disease 2
• Fetal outcome is less favorable, but pregnancies reaching week 20 of gestation are associated with acceptable fetal prognosis even when 76% had preterm delivery 2
• Vitamin K antagonists are absolutely contraindicated during pregnancy due to risk of fetal hemorrhage and teratogenicity 1
• Switch to LMWH with periodic monitoring of anti-Xa activity as soon as pregnancy is confirmed 2
• VKAs are acceptable during breastfeeding 1

Acute vs. Chronic Presentation

• In acute form of BCS (short history and absence of extensive fibrosis or cirrhosis): early portal decompression is mandatory, with low risk of shunt thrombosis and good long-term results 4
• In chronic form of BCS: risk of shunt thrombosis is high and long-term results are worse; liver transplantation must be considered earlier 4
• Rotterdam Class III patients should be considered for early TIPS 1

Critical Pitfalls to Avoid

• Do not delay anticoagulation even in the presence of varices—ensure adequate primary prophylaxis for varices is in place first 1
• Do not use bare metal stents for TIPS; always use PTFE-covered stents 1
• Do not perform hepatic artery embolization, as it is associated with significant morbidity and is contraindicated in patients with portosystemic shunting 5
• Duration of symptoms before intervention matters: longer duration (>100 days) combined with myeloproliferative disorder and cirrhosis predicts 100% shunt thrombosis risk 4
• Continue anticoagulation and treatment of underlying cause after TIPS placement to enhance prognosis 1