What is the recommended treatment approach for a patient with suspected Budd-Chiari syndrome, particularly those with a history of thrombophilic conditions or liver disease?

Treatment of Budd-Chiari Syndrome

Immediate Management: Anticoagulation First

All patients with Budd-Chiari syndrome must receive lifelong anticoagulation therapy initiated immediately upon diagnosis, regardless of the presence of varices or ascites. 1

• Start with low molecular weight heparin (LMWH) for at least 5-7 days, then transition to oral vitamin K antagonists (warfarin) targeting an INR of 2-3 1
• Overlap VKA with parenteral anticoagulation for at least 5 days, continuing 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 portal hypertension prophylaxis 1

Concurrent Initial Measures

Treat the underlying prothrombotic condition immediately alongside anticoagulation. 2, 1

• For myeloproliferative neoplasms: use hydroxyurea or alpha interferon to normalize peripheral blood cell counts 2
• For polycythemia vera: maintain hematocrit <45% 2
• For paroxysmal nocturnal hemoglobinuria: consider long-term eculizumab 2
• Manage ascites and varices following the same treatment recommendations as for cirrhosis 2, 1

Stepwise Interventional Algorithm

The European Association for the Study of the Liver recommends a sequential approach: medical treatment → angioplasty/stenting → TIPS → liver transplantation. 2, 1

Step 1: Angioplasty/Stenting (First-Line Intervention)

• Indicated for patients with short, focal stenoses of hepatic veins or IVC 1
• Present in 60% of patients with IVC obstruction and 25-30% with hepatic vein obstruction 1
• Stent placement 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 (Second-Line Intervention)

TIPS using PTFE-covered stents exclusively should be performed after failure of medical treatment or when angioplasty/stenting is ineffective or technically impossible. 1

• Symptom resolution exceeds 70% with 5-year survival rates exceeding 70% 1
• PTFE-covered stents improve primary patency compared to bare stents 1
• Risk of hepatic encephalopathy is approximately 15% 1
• Also indicated for fulminant Budd-Chiari syndrome 1
• Perform Doppler ultrasound early after placement, then every 6 months to detect thrombosis or dysfunction 1

Step 3: Liver Transplantation (Salvage Therapy)

Liver transplantation is reserved for patients who fail all other therapeutic options. 1

• Best results achieved when thrombosis is limited to hepatic veins and the underlying cause can be corrected by liver replacement 1
• Immediate referral to transplant center for patients presenting with fulminant hepatic failure 1
• Consider urgent TIPS placement as bridge to transplantation 1
• Patients with BCS-TIPS score >7 consistently predict poor outcomes and should be considered for transplantation 1

Critical Management Requirements

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

Essential Diagnostic Workup

Complete thrombophilia screening is mandatory before initiating treatment. 2

• Test for protein S, protein C, antithrombin levels, Factor V Leiden mutation, prothrombin G20210A gene variant 2
• Test for antiphospholipid antibodies; if positive, repeat after 12 weeks 2
• Test for JAK2V617F mutation in all patients, even with normal peripheral blood cell counts 2
• If JAK2V617F negative, perform calreticulin mutation screening 2
• If both negative, consider bone marrow histology and refer to hematologist 2
• Screen for paroxysmal nocturnal hemoglobinuria 2
• Investigate for local risk factors including intra-abdominal inflammatory conditions and malignancies 2

Special Populations

Pregnancy

• LMWH is the anticoagulant of choice during pregnancy 1
• VKAs are absolutely contraindicated during pregnancy due to fetal hemorrhage risk and teratogenicity 1
• VKAs are acceptable during breastfeeding 1

Rotterdam Class III Patients

• Consider early TIPS, though this requires further validation 1

Monitoring and Follow-Up

• Check INR at least weekly during initiation phase; once stable, extend to monthly intervals 1
• Screen for hepatocellular carcinoma as patients may develop hypervascular liver nodules 1
• Continue anticoagulation indefinitely even after successful interventions 1, 3, 4