Hepatic veno-occlusive disease


Hepatic veno-occlusive disease or veno-occlusive disease with immunodeficiency is a potentially life-threatening condition in which some of the small veins in the liver are obstructed. It is a complication of high-dose chemotherapy given before a bone marrow transplant and/or excessive exposure to hepatotoxic pyrrolizidine alkaloids. It is classically marked by weight gain due to fluid retention, increased liver size, and raised levels of bilirubin in the blood. The name sinusoidal obstruction syndrome is preferred if VODI happens as a result of chemotherapy or bone marrow transplantation.
Apart from chemotherapy, VODI may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids, and has been described as part of a rare hereditary disease called hepatic venoocclusive disease with immunodeficiency.

Signs and symptoms

Features of VODI include weight gain, tender enlargement of the liver, ascites, and yellow discoloration of the skin; it often is associated with acute kidney failure.

Pathophysiology

In the BMT setting, VODI is felt to be due to injury to the hepatic venous endothelium from the conditioning regimen.Toxic agents causing veno-occlusive disease include plants as well as the medication cyclophosphamide.

Diagnosis

Doppler ultrasound of the liver is typically utilized to confirm or suggest the diagnosis. Common findings on liver doppler ultrasound include increased phasicity of portal veins with eventual development of portal flow reversal. The liver is usually enlarged but maintained normal echogenicity. A liver biopsy is required for a definitive diagnosis.

Treatment

Treatment generally includes supportive care including pain management and possibly diuretics. In those with severe disease due to a bone marrow transplant, defibrotide is a proposed treatment. It has been approved for use in severe cases in Europe and the United States. A placebo controlled trial, however, has not been done as of 2016.

Prognosis

Mild disease has a risk of death of about 10% while moderate disease has a risk of death of 20%. When it occurs as a result of bone marrow transplant and multiorgan failure is present, the risk of death is greater than 80%.

History

The first report on veno-occlusive disease, in 1920, was as a result of senecio poisoning in South Africa. Subsequent reports were mostly in Jamaicans who had consumed herbal teas. With the advent of bone marrow transplantation, most cases since its introduction have been in those undergoing treatment for leukemia.