Sinusoidal Obstruction Syndrome

Sinusoidal obstruction syndrome (SOS, hepatic veno occlusive disease) is injury to hepatic sinusoidal endothelium and hepatocytes causing sinusoidal obstruction, portal hypertension and liver dysfunction, without thrombosis of larger hepatic veins.

• Causes: myeloablative haematopoietic stem cell transplant conditioning (busulfan, cyclophosphamide, total body irradiation), gemtuzumab and inotuzumab ozogamicin, oxaliplatin, dactinomycin, pyrrolizidine alkaloids (herbal teas, contaminated grain), azathioprine, 6 thioguanine.
• Incidence after transplant is 5 to 15%, higher with pre existing liver disease, prior gemtuzumab, second transplant and unrelated donor.
• Onset is usually within 21 days of transplant, but late onset occurs.
• Severe disease with multi organ failure has mortality over 80% untreated.

• Weight gain from fluid retention, painful tender hepatomegaly, ascites and jaundice (bilirubin 2 mg/dL or more).
• Refractory thrombocytopenia with platelet transfusion need.
• Severe: renal dysfunction, hypoxia, encephalopathy, multi organ failure.
• Pyrrolizidine induced disease may be subacute or chronic.

• Clinical criteria (EBMT): classical (within 21 days) bilirubin 2 mg/dL or more with two of painful hepatomegaly, weight gain over 5%, ascites. Late onset after day 21 with histology or Doppler evidence.
• Doppler ultrasound: hepatomegaly, ascites, reduced or reversed portal flow, gallbladder wall thickening.
• Severity grading: mild to very severe by bilirubin, transaminases, weight gain, renal function.
• Exclude acute graft versus host disease, sepsis, drug toxicity, viral hepatitis, cardiac failure.
• Transjugular liver biopsy with hepatic venous pressure gradient above 10 mmHg when diagnosis is unclear.

• Defibrotide 6.25 mg/kg IV every 6 hours for at least 21 days (until resolution). Early start improves day 100 survival (about 59% vs 31% historical). Hold with active bleeding and anticoagulation.
• Supportive: restrict sodium and fluid, albumin and diuretics (furosemide, spironolactone), paracentesis, avoid hepatotoxic and nephrotoxic drugs, renal replacement therapy for refractory overload, ventilation if needed.
• Methylprednisolone 1 mg/kg/day has limited evidence.
• Prevention in transplant: ursodeoxycholic acid 12 mg/kg daily from conditioning to day 90, reduced intensity conditioning, defibrotide prophylaxis in high risk patients.
• TIPS and transplant have limited roles.
• Pyrrolizidine toxicity: stop exposure, supportive care.
• Monitor daily weight, bilirubin and abdominal girth.