Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a condition involving the obstruction of small veins and capillaries within the liver. This blockage impedes proper blood flow through the liver, leading to a backup of blood, increased pressure, and potential liver damage. VOD is not an independent illness but a complication that arises from other medical treatments or exposures.
Causes and Risk Factors
The most common cause of VOD is the high-dose chemotherapy or radiation used in a conditioning regimen before a hematopoietic stem cell transplant (HSCT). These treatments can damage the endothelial cells lining the liver’s small blood vessels, leading to inflammation, clotting, and obstruction. The incidence after an HSCT can range from 2% to 15%.
Certain chemotherapeutic agents, like cyclophosphamide and busulfan, are frequently associated with VOD. Radiation therapy directed at the abdomen can also cause the endothelial injury that starts the disease. A less frequent cause is the ingestion of pyrrolizidine alkaloids, toxic compounds found in some herbal teas and traditional medicines.
Pre-existing liver conditions, such as active viral hepatitis or cirrhosis, increase a person’s susceptibility. Allogeneic transplants, which use stem cells from a donor, carry a higher risk than autologous transplants using the patient’s own cells. The intensity of the conditioning regimen is another factor, with more aggressive therapies elevating the risk.
Signs and Symptoms
The symptoms of VOD typically appear one to four weeks after a stem cell transplant begins. One of the primary indicators is rapid, unexplained weight gain resulting from the body retaining fluid. This fluid retention often manifests as ascites, which is a noticeable swelling of the abdomen.
Another hallmark sign is hepatomegaly, the enlargement of the liver. This swelling can cause pain and tenderness in the upper right quadrant of the abdomen. A third common symptom is jaundice, a condition that causes the skin and whites of the eyes to turn yellow.
Jaundice occurs because the damaged liver cannot properly process bilirubin, a yellow pigment formed from the breakdown of red blood cells. In more serious instances, the kidneys may also begin to fail, contributing to swelling in the arms and legs.
Diagnosis Process
The diagnosis of VOD is often made clinically, based on characteristic signs and symptoms in a patient with a known risk factor, like a recent stem cell transplant. Physicians look for the classic triad of symptoms: jaundice, painful hepatomegaly, and fluid retention with weight gain. The timing of symptom onset, usually within 20 days post-transplant, is a strong indicator.
To support the diagnosis and rule out other liver conditions, specific criteria like the Baltimore or modified Seattle criteria are used. These frameworks require elevated bilirubin along with at least two other findings, such as hepatomegaly, ascites, or significant weight gain.
Blood tests are performed to assess liver function by measuring bilirubin levels. A Doppler ultrasound is a useful non-invasive tool that can detect changes in blood flow within the portal vein. In uncertain cases, a transjugular liver biopsy can provide definitive evidence of sinusoidal obstruction.
Treatment Approaches
Management of VOD begins with supportive care to alleviate symptoms and prevent further complications. This approach focuses on careful management of the patient’s fluid balance, often involving sodium and fluid restriction. Diuretic medications may also be used to help the kidneys excrete excess salt and water, and pain management is provided for liver discomfort.
For patients with a confirmed diagnosis, particularly those with more severe disease, the medication defibrotide is the primary treatment. Defibrotide is believed to work by protecting the endothelial cells that line blood vessels from further damage and may help break down small blood clots. It is administered intravenously for severe VOD following an HSCT.
In severe cases that do not respond to medication, more invasive procedures might be considered to relieve high pressure in the liver’s veins. A transjugular intrahepatic portosystemic shunt (TIPS) creates a new channel to connect the portal vein directly to a hepatic vein. This shunt allows blood to bypass the obstructed sinusoids, reducing pressure and its complications.
Disease Severity and Prognosis
Veno-occlusive disease is categorized as mild, moderate, or severe, based on the degree of liver dysfunction and its impact on other organs. This classification helps guide treatment and provides insight into the likely outcome.
Mild cases of VOD may resolve with only supportive care. In these instances, the liver injury is limited, and with careful management of fluids and symptoms, the liver can often recover its function over time.
Severe VOD is defined by the persistence of symptoms and the development of multi-organ failure, often involving the kidneys and lungs. This form of the disease is associated with a high mortality rate, which can exceed 80% in the most severe cases.