Veno-Occlusive Disease (VOD), also known as Sinusoidal Obstruction Syndrome (SOS), is a serious and potentially life-threatening condition affecting the liver’s small blood vessels. This rare disorder is characterized by damage to the liver’s internal structure, which rapidly leads to severe liver dysfunction. VOD/SOS is most frequently recognized as a complication following intense medical therapies, requiring prompt intervention due to its capacity to quickly progress.
How VOD Affects the Liver
VOD is fundamentally a vascular disorder initiated by toxic injury to the endothelial cells lining the hepatic sinusoids. Sinusoids are the liver’s specialized capillaries where blood mixes before flowing into the central veins. The toxic insult causes these delicate endothelial cells to detach, swell, and slough off.
The detached cellular debris and blood components embolize to block the terminal hepatic venules and sinusoids. This obstruction prevents blood from efficiently exiting the liver, causing it to back up and creating post-sinusoidal portal hypertension. The resulting congestion leads to swelling and necrosis of the surrounding liver cells, driving the clinical manifestations of the syndrome.
Primary Causes and Risk Factors
The most common context for VOD/SOS is high-dose chemotherapy and radiation used as a conditioning regimen before a hematopoietic stem cell transplant (HSCT). The cytotoxic agents delivered during this preparation phase are the direct cause of the endothelial cell damage. Specific chemotherapy agents, such as Busulfan and Cyclophosphamide, are known to carry a higher risk.
The risk of developing VOD is also influenced by pre-existing patient factors and the type of transplant. Prior liver disease, like pre-transplant elevated liver enzymes or hepatic fibrosis, increases susceptibility to the toxic effects of the conditioning regimen. Patients who receive an allogeneic (donor) stem cell transplant face a higher risk compared to those receiving an autologous (self) transplant. Non-transplant-related causes exist, including exposure to hepatotoxic substances found in some herbal remedies and teas.
Identifying the Signs and Symptoms
The clinical presentation of VOD/SOS typically emerges rapidly, often within the first three weeks following a stem cell transplant. The condition is recognized by a classic diagnostic triad. This triad includes painful enlargement of the liver, known as tender hepatomegaly, resulting from severe congestion and swelling.
The second hallmark is the rapid accumulation of fluid, manifesting as unexplained weight gain and abdominal swelling (ascites). This fluid retention occurs due to portal hypertension and subsequent leakage of fluid from the congested vessels. The third element is jaundice, a yellowing of the skin and eyes, caused by rising levels of bilirubin in the blood. Diagnostic imaging, such as a Doppler ultrasound, supports diagnosis by revealing changes in blood flow, including reduction or reversal of flow in the portal veins.
Treatment and Recovery
Management of VOD/SOS focuses on two main approaches: supportive care and targeted intervention. Supportive measures manage complications arising from liver congestion, including controlling fluid balance and managing pain. Diuretics are often used to address rapid weight gain and ascites by encouraging the removal of excess fluid.
For severe cases, a specific medication called Defibrotide is used. It is approved for treatment in patients who develop kidney or lung dysfunction after HSCT. Defibrotide works by protecting damaged endothelial cells, restoring the balance between clot formation and breakdown, and promoting the dissolution of existing clots. While the prognosis is generally good for mild or moderate cases, severe VOD/SOS complicated by multi-organ failure has a higher mortality rate.