How should I diagnose and manage a patient with acute abdominal pain, hepatomegaly, ascites, worsening liver function and risk factors (hypercoagulable state, pregnancy, oral contraceptive use, malignancy, recent abdominal surgery) suggestive of Budd‑Chiari syndrome?

Budd-Chiari Syndrome: Diagnosis and Management

In a patient presenting with acute abdominal pain, hepatomegaly, ascites, worsening liver function, and risk factors for hypercoagulability, immediately obtain Doppler ultrasound to diagnose Budd-Chiari syndrome, initiate anticoagulation as soon as the diagnosis is confirmed, and refer urgently to a specialized hepatology center with interventional radiology and liver transplant capabilities. 1

Diagnostic Approach

Initial Imaging

• Doppler ultrasound is the first-line diagnostic test with sensitivity >75% for detecting hepatic venous outflow obstruction 1
• Look for obstruction or thrombosis of hepatic veins, IVC involvement, reversal of flow in hepatic veins, and development of collateral vessels 1, 2
• If Doppler ultrasound is negative but clinical suspicion remains high, proceed immediately to MRI or CT with contrast for diagnostic confirmation 1
• Re-evaluate with an expert radiologist if imaging studies are negative but suspicion persists 1

Mandatory Laboratory Workup

Complete thrombophilia screening must be performed in all patients 3, 2:

• Myeloproliferative neoplasm testing: JAK2V617F mutation (present in ~29-49% of BCS patients), and if negative, calreticulin mutation screening 4, 2
• Inherited thrombophilias: Factor V Leiden mutation, prothrombin G20210A gene variant, protein C/S deficiency, antithrombin deficiency 1, 2
• Acquired thrombophilias: Antiphospholipid antibodies (requires repeat testing after 12 weeks for confirmation) 2
• Paroxysmal nocturnal hemoglobinuria: Flow cytometry 2

The etiology is multifactorial in 46% of patients, with multiple concurrent prothrombotic factors present 2. Myeloproliferative neoplasms are the single most important cause, occurring in approximately 49% of cases 4, 2.

Immediate Management

Anticoagulation - The Cornerstone of Treatment

Initiate anticoagulation immediately upon diagnosis and continue indefinitely 1, 3:

• Start with low molecular weight heparin (LMWH) for at least 5-7 days 3
• Overlap with vitamin K antagonist (warfarin) targeting INR 2-3 3
• Continue parenteral anticoagulation until INR has been 2.0-3.0 for two consecutive days 3
• Portal hypertension complications (varices, ascites) are NOT contraindications to anticoagulation when adequately treated 1, 3

Critical caveat: Bleeding complications have decreased from 50% in older studies to 17% with better management of anticoagulation during invasive procedures and adequate portal hypertension prophylaxis 3.

Special Population: Pregnancy

• Vitamin K antagonists are absolutely contraindicated during pregnancy due to fetal hemorrhage risk and teratogenicity 1
• Switch immediately to LMWH with periodic monitoring of anti-Xa activity as soon as pregnancy is confirmed 1
• Maternal outcomes are excellent with well-controlled disease, though fetal outcomes are less favorable with 76% preterm delivery rate 1, 3
• VKAs are acceptable during breastfeeding 1

Treatment of Underlying Prothrombotic Conditions

Concurrent treatment of the underlying cause is mandatory 3:

• Myeloproliferative neoplasms: Hydroxyurea or alpha interferon to normalize peripheral blood counts 3
• Polycythemia vera: Maintain hematocrit <45% 4, 3
• Paroxysmal nocturnal hemoglobinuria: Consider long-term eculizumab 3

Portal Hypertension Management

Manage ascites and varices following the same guidelines as for cirrhosis 1, 3:

• Primary prophylaxis with non-selective beta-blockers or endoscopic variceal ligation for high-risk varices 4
• Esophageal varices occur in 58% of BCS patients 4
• Variceal bleeding is a significant complication, particularly when primary prophylaxis is not provided 4

Stepwise Interventional Algorithm

All BCS patients must be managed in specialized centers with expertise in hepatology, interventional radiology, and formal links to liver transplant centers 3. The treatment follows a sequential approach with increasing invasiveness 3:

Step 1: Medical Management

• Anticoagulation + treatment of underlying cause + portal hypertension management 3
• Monitor response clinically and with Doppler ultrasound 3

Step 2: Angioplasty/Stenting

Indicated for patients with short, focal stenoses 3:

• Present in 60% of patients with IVC obstruction and 25-30% with hepatic vein obstruction 3
• Most effective when physiological drainage can be re-established 3
• Stent placement reduces re-stenosis rates compared to angioplasty alone 3
• Caution: Misplacement of stents may compromise subsequent TIPS or liver transplantation 3

Step 3: Transjugular Intrahepatic Portosystemic Shunt (TIPS)

TIPS is indicated when 3:

• Medical treatment fails
• Angioplasty/stenting is ineffective or technically impossible
• Fulminant BCS presentation 3
• Recurrent variceal bleeding despite adequate endoscopic and medical treatment 4

TIPS outcomes 3:

• Symptom resolution exceeds 70% 3
• 5-year survival rates exceed 70% 3
• OLT-free survival at 1 and 5 years is 88% and 78% respectively 3
• Hepatic encephalopathy risk is approximately 15% 3

Technical considerations:

• Use PTFE-covered stents exclusively for improved primary patency 3
• In >45% of cases, a transcaval approach may be required due to complete hepatic vein thrombosis, requiring specialized expertise 3
• Perform Doppler ultrasound early post-procedure and then every 6 months to detect thrombosis or dysfunction 3

Step 4: Liver Transplantation

Reserved for patients who fail all other therapeutic options 3:

• Best results when thrombosis is limited to hepatic veins and underlying cause can be corrected by transplantation 3
• Immediate referral to transplant center for patients with fulminant hepatic failure 3
• Consider urgent TIPS as bridge to transplantation 3
• Survival after liver transplantation is similar to that obtained with TIPS 3
• Post-transplant anticoagulation must be initiated early and maintained lifelong to prevent BCS recurrence, except when the prothrombotic disorder is corrected by transplantation (e.g., most inherited thrombophilias) 1

Prognostic Considerations

• BCS-TIPS score >7 consistently predicts poor outcomes and should prompt consideration of liver transplantation 3
• Approximately 15% of cases have simultaneous portal vein thrombosis at presentation, which worsens prognosis 2
• Development of hepatocellular carcinoma or progression of hematological disease may modify prognosis 1
• Screen for HCC with MRI using hepatospecific contrast agents, as BCS patients may develop hypervascular liver nodules with atypical imaging characteristics 3

Common Pitfalls to Avoid

• Do not delay anticoagulation while awaiting complete thrombophilia workup 1, 3
• Do not withhold anticoagulation due to presence of varices or ascites when these are adequately managed 1, 3
• Do not perform surgical shunts as first-line intervention; they have higher morbidity/mortality without survival advantage compared to TIPS 3
• Do not miss pregnancy testing in reproductive-aged women before initiating VKA therapy 1
• Do not overlook myeloproliferative neoplasm testing even when another clear causative factor is identified, as multiple risk factors coexist in 46% of patients 2