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Venoocclusive disease (VOD)
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Sinusoidal obstruction syndrome (SOS)
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Stem cell transplantation and high-dose chemotherapy
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Herbal medicines containing pyrrolizidine alkaloids
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Rare complication of liver transplantation
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Rare causes of sinusoidal obstruction: Sickle cell crisis,
Plasmodium falciparum malaria, extensive infiltration by neoplastic cells
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Older age and poor performance status
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HLA disparity in allogeneic stem cell transplant
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Preexisting liver dysfunction
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Prior abdominal radiation
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Pretransplant use of acyclovir or vancomycin
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High-dose busulphan and cyclophosphamide therapy
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Injury to sinusoidal endothelial cells is important initial event; hence, preferred term is SOS
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Major damage occurs in zone 3, which has high concentration of cytochrome P450 enzymes that metabolize many chemotherapeutic agents
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Depletion of glutathione, also predominantly present in centrizonal location, plays role in hepatocyte necrosis
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SOS in stem cell transplantation
Typically occurs in 1st 3 weeks
Triad of hyperbilirubinemia, weight gain, and painful hepatomegaly
Plasma levels of plasminogen activator inhibitor-1 are often elevated
Attenuated or reverse flow in portal vein on Doppler ultrasound
Wedged hepatic venous pressure gradient (WHVPG) > 10 mmHg has 91% specificity and 52% sensitivity
Diagnosis often based on clinical criteria, biopsy reserved for unclear cases
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Use of pharmacokinetics to monitor drug levels with intent of minimizing hepatic injury
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Fibrinolytic agents such as recombinant tissue plasminogen activator and anticoagulants like heparin
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Antiinflammatory agents such as ursodiol and pentoxifylline
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Endothelial protective agents such as prostaglandin E1 and defibrotide
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Glutathione and N-acetyl cysteine supplementation
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Mild disease: No significant adverse effect from liver dysfunction with complete resolution
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Moderate disease: Requiring therapy but with eventual complete resolution
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Severe: Dismal outcome, mortality approaching 100%
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Adverse prognostic factors: Ascites, multiorgan failure, WHVPG > 20 mmHg
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Liver biopsy is done through transjugular route; percutaneous biopsy is contraindicated given high risk for bleeding
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Changes can be patchy in early disease leading to false-negative results
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Subendothelial edema, red cell extravasation, fibrin deposition in central vein and sinusoids
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Narrowing of venular lumen leads to sinusoidal dilatation and hepatocyte necrosis
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Fibrosis develops in sinusoids and venular wall
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Eventually leads to venular obliteration, extensive hepatocellular necrosis, and widespread fibrosis
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Also causes acute liver dysfunction after stem cell transplant
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Bile duct damage and apoptosis are not seen in VOD
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Centrizonal hepatocellular damage is not characteristic of GVHD
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Venular luminal compromise, obliteration absent in hepatic venous outflow obstruction
1.Palladino, M, et al. Severe veno-occlusive disease after autologous peripheral blood stem cell transplantation for high-grade non-Hodgkin lymphoma: report of a successfully managed case and a literature review of veno-occlusive disease. Clin Transplant . 2008; 22(6):837–841.
2.Karoui, M, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg . 2006; 243(1):1–7.
3.Kumar, S, et al. Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation. Mayo Clin Proc . 2003; 78(5):589–598.
4.Wadleigh, M, et al. Hepatic veno-occlusive disease: pathogenesis, diagnosis and treatment. Curr Opin Hematol . 2003; 10(6):451–462.
5.Dhillon, AP, et al. Hepatic venular stenosis after orthotopic liver transplantation. Hepatology . 1994; 19(1):106–111.
Related Diagnostic Pathology Hepatobiliary and Pancreas
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leads to partial occlusion of the lumen of a small hepatic vein in venoocclusive disease. These characteristic lesions may not be evident in biopsies.
in hepatic sickle cell crisis is shown. This is a rare phenomenon but can cause sinusoidal obstruction syndrome and present in an acute fashion.
