What is the treatment for veno occlusive disease (VOD) of the liver?

Treatment of Hepatic Veno-Occlusive Disease (VOD/SOS)

Defibrotide 6.25 mg/kg intravenously every 6 hours (as a 2-hour infusion) is the definitive treatment for hepatic veno-occlusive disease with renal or pulmonary dysfunction following hematopoietic stem cell transplantation. 1

FDA-Approved Pharmacologic Treatment

Defibrotide is FDA-approved and represents the only proven effective therapy for VOD/SOS with multiorgan dysfunction. 1

• Administer defibrotide at 6.25 mg/kg every 6 hours as a 2-hour intravenous infusion 1
• Treat for a minimum of 21 days; if signs and symptoms have not resolved after 21 days, continue treatment until resolution 1
• This dosing regimen (25 mg/kg/day total) demonstrated 54% overall day +100 survival in severe VOD/SOS with multiorgan failure, a condition that otherwise carries >80% mortality 2, 3
• The British Committee for Standards in Haematology and British Society for Blood and Marrow Transplantation recommend defibrotide for treatment of VOD/SOS in both adults and children (Grade 1B recommendation) 4

Critical Contraindications and Monitoring

Do not administer defibrotide with concomitant systemic anticoagulant or fibrinolytic therapy. 1

• Defibrotide is contraindicated in patients receiving systemic anticoagulation or fibrinolytic therapy due to enhanced bleeding risk 1
• Monitor patients closely for hemorrhage; withhold or discontinue defibrotide if significant bleeding occurs 1
• Discontinue immediately if severe or life-threatening hypersensitivity reactions occur 1

Supportive Care Measures

Meticulous fluid management is essential, as VOD/SOS patients develop weight gain >5%, ascites, and third-spacing. 5, 4

• Judicious clinical care, particularly careful management of fluid balance, is recommended alongside defibrotide therapy 4
• Manage complications of portal hypertension (ascites, hepatomegaly) as you would in cirrhotic patients 6
• Salt restriction and diuretics may be necessary for fluid overload 6

Therapies NOT Recommended

Tissue plasminogen activator should not be used due to unacceptable hemorrhage risk (Grade 1B). 4

• N-acetylcysteine is not routinely recommended due to lack of efficacy (Grade 1A) 4
• Prostaglandin E1 is not recommended due to lack of efficacy and toxicity (Grade 1B) 4
• Pentoxifylline is not recommended due to lack of efficacy (Grade 1A) 4
• Heparin (unfractionated and low molecular weight) is not suggested due to increased bleeding risk (Grade 2B) 4
• Antithrombin is not suggested due to lack of efficacy (Grade 2B) 4

Salvage Interventions for Refractory Cases

Early consultation with critical care and hepatology specialists is mandatory for severe VOD/SOS, particularly when defibrotide fails. 4

• Transjugular intrahepatic portosystemic shunt (TIPS) may be considered in refractory cases not responding to defibrotide 4
• Liver transplantation represents a salvage option for patients with treatment failure, though this is rarely feasible in the post-HSCT setting 4
• These interventions should be discussed early in the disease course, not delayed until the patient is moribund 4

Diagnostic Confirmation Before Treatment

Diagnosis relies on Seattle or Baltimore clinical criteria (bilirubin ≥2 mg/dL, hepatomegaly, weight gain >5%, ascites) after excluding other causes. 5

• Transjugular liver biopsy with hepatic venous pressure gradient (HVPG) measurement provides definitive diagnosis when clinical criteria are uncertain 5
• HVPG >10 mmHg has 91% specificity and >85% positive predictive value for VOD/SOS in HSCT patients 5
• Doppler ultrasound is first-line imaging to exclude other disorders but has lower sensitivity than clinical criteria 5
• Up to 20% of VOD/SOS cases cannot be diagnosed with certainty using clinical features alone, necessitating biopsy in unclear cases 5

Common Pitfalls to Avoid

• Do not delay defibrotide initiation while pursuing diagnostic confirmation in patients with classic clinical presentation post-HSCT, as early treatment improves outcomes 3, 4
• Do not continue systemic anticoagulation when starting defibrotide—this is an absolute contraindication 1
• Do not use tissue plasminogen activator despite its theoretical appeal; hemorrhagic complications are prohibitive 4
• Do not stop defibrotide at 21 days if VOD/SOS has not resolved; continue until clinical resolution 1