Hepatic Veno-Occlusive Disease (VOD): Understanding SOS

Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 15, 2026

Quick Answer: What is hepatic veno-occlusive disease (VOD)?

Hepatic veno-occlusive disease (VOD) is a severe liver disorder that typically develops within the first few weeks after a stem cell transplant. Conditioning treatments such as intense chemotherapy or radiation damage the cells lining the liver's smallest blood vessels, causing blockage, high blood pressure in the liver and organ dysfunction. Untreated, it can progress to multi-organ failure and death.

What the research says

• Ursodiol is the best-supported preventive drug. A Cochrane review of 14 randomized trials found ursodeoxycholic acid may reduce the incidence of hepatic VOD after stem cell transplant (risk ratio 0.60, 95% CI 0.40 to 0.88), though the evidence was low quality and the review found insufficient evidence to support heparin, low-molecular-weight heparin, or defibrotide for prevention (Cheuk et al., Cochrane Database Syst Rev, 2015) [2].

• Defibrotide prevention shows promise in pooled studies. A meta-analysis of 20 studies (3,005 patients) found VOD/SOS occurred in 5% of patients given intravenous defibrotide prophylaxis versus 16% of controls in comparative studies (risk ratio 0.30, 95% CI 0.12 to 0.71) (Corbacioglu et al., Clin Drug Investig, 2022) [3].

• No single prevention strategy has clearly won. A network meta-analysis of randomized trials found ursodiol (odds ratio 0.38, 95% CI 0.14 to 1.06) and defibrotide (odds ratio 0.64, 95% CI 0.23 to 1.67) were each associated with fewer cases, but neither reached statistical significance (Sousa-Pimenta et al., J Clin Med, 2024) [4].

Key Takeaways

The Mechanism of Sinusoidal Obstruction

The liver contains a complex network of microscopic blood vessels called sinusoids. During the preparation for a stem cell transplant, patients receive high-intensity “conditioning” therapy designed to destroy abnormal cells and make room for new stem cells. Unfortunately, these toxic treatments can also damage the delicate sinusoidal endothelial cells that line the liver's tiny vessels [1].

When these cells are damaged, the vessel lining begins to leak, and debris accumulates within the narrow pathways. This “traffic jam” restricts blood flow, leading to increased pressure within the liver's vascular system and eventually causing liver failure [1]. This condition, now frequently referred to as Sinusoidal Obstruction Syndrome (SOS), can extend its damaging effects to other vital organs, including the heart, lungs, and brain [1].

Recognizing Early Warning Signs

Because VOD is so serious, medical teams monitor transplant patients closely in the hospital for several weeks. The first signs of the condition often appear within the first 12 to 21 days after treatment [1]. A sudden, unexplained drop in platelet levels is often the earliest indicator that the liver is under stress [1].

Physical symptoms that demand immediate attention include:

1. Abdominal Swelling (Ascites): Rapid fluid buildup in the belly and sudden weight gain [1].

2. Liver Pain: Discomfort or tenderness in the upper right quadrant of the abdomen [1].

3. Jaundice: A distinct yellowing of the skin, the whites of the eyes, and mucous membranes [1].

4. Cognitive Changes: Confusion or difficulty thinking, which may indicate that liver dysfunction is affecting the brain [1].

Risk Factors and Grading

The overall risk of developing VOD after a stem cell transplant is estimated at 5% to 15% [1]. However, several factors can significantly increase this probability. Infants are at the highest risk, while in adults, the risk increases with age. The type of transplant also matters; allogeneic transplants (using donor cells) are more likely to lead to VOD than autologous transplants [1].

Preexisting liver disease and the use of specific chemotherapy drugs during previous cancer treatments further elevate the risk [1]. Healthcare providers use a grading system to categorize the severity of VOD as either mild/moderate or severe/very severe [1]. This grading helps determine the intensity of the required medical intervention.

Treatment Strategies and Prevention

Management of VOD is primarily conducted in a hospital setting. For mild to moderate cases, supportive care involving restricted fluid and salt intake, along with diuretics (water pills), may be sufficient [1]. For severe cases, the primary treatment is defibrotide, an FDA-approved IV medication that helps protect the vessel linings and restore blood flow [1].

In the most critical scenarios, advanced procedures like a transjugular intrahepatic portosystemic stent-shunt (TIPS) or even a liver transplant may be considered [1]. Prevention is also a major focus; providers may use prophylactic medications like ursodeoxycholic acid in adults or defibrotide in children to shield liver cells before the transplant begins [1].

Conclusion

Hepatic veno-occlusive disease remains one of the most challenging complications of stem cell therapy, but advancements in treatment and prevention have significantly improved the outlook for patients. Through rigorous monitoring and early intervention, the risks to long-term liver health can be managed effectively.

FAQ

What is the difference between VOD and SOS?

They are two names for the same condition. VOD refers to the blockage of veins, while SOS emphasizes the obstruction of the liver's sinusoids. [1]

Is VOD common?

It affects approximately 5% to 15% of patients who undergo a stem cell transplant. [1]

Can VOD happen if I don't have a transplant?

While rare, it can occur after certain high-dose cancer treatments that are unrelated to a transplant. [1]

Why are infants at higher risk?

The delicate nature of an infant's liver and their response to intense conditioning therapy makes them more susceptible to VOD. [1]

What is “conditioning” treatment?

It is the high-dose chemotherapy or radiation given before a transplant to kill cancer cells and suppress the immune system. [1]

How quickly do VOD symptoms appear?

Most symptoms start around 12 days after the transplant, but they can appear anytime within the first few weeks. [1]

What is ascites?

It is the medical term for the accumulation of fluid in the abdominal cavity, a common sign of VOD. [1]

How does VOD affect the brain?

When the liver fails to filter toxins, they can build up in the blood and cause confusion or cognitive issues. [1]

Is VOD always fatal?

No. While severe cases were historically very dangerous, modern treatments like defibrotide have greatly improved survival. [1]

What is defibrotide?

It is an FDA-approved medication that helps protect the lining of blood vessels and treat severe VOD. [1]

How is VOD diagnosed?

Diagnosis is based on clinical symptoms, weight gain, liver function tests, and ultrasound imaging. [1]

Can an ultrasound show VOD?

Yes, doctors use ultrasound to look for changes in blood flow and signs of liver enlargement. [1]

What is a liver biopsy?

It is a procedure to take a small sample of liver tissue, though it is only used in VOD if it is deemed safe for the patient. [1]

What is an allogeneic transplant?

A transplant where the stem cells come from a donor rather than the patient's own body. [1]

Does age affect VOD risk?

Yes, both infants and older adults are at a higher risk for developing the condition. [1]

What are “water pills” used for in VOD?

Diuretics help the body get rid of the excess fluid that builds up in the abdomen and tissues. [1]

Can VOD damage the lungs?

Yes, severe VOD can lead to multi-organ dysfunction, including respiratory issues. [1]

What is GvHD?

Graft-versus-host disease is when donor stem cells attack the recipient's body; some treatments for GvHD can increase VOD risk. [1]

Is weight gain a sign of VOD?

Yes, sudden and rapid weight gain due to fluid retention is a hallmark symptom. [1]

Can VOD be prevented?

Not always, but medications like ursodiol or defibrotide can be used preventatively in high-risk patients. [1]

What is a “sinusoid” in the liver?

Sinusoids are the tiny, specialized blood vessels where the liver filters blood. [1]

What is the survival rate for severe VOD?

Historically, mortality was as high as 80%, but this has decreased with better management and new drugs. [1]

Can VOD cause heart problems?

Yes, the systemic impact of liver failure and fluid overload can strain the heart. [1]

What is ursodeoxycholic acid?

Also known as ursodiol, it is a medication that can help protect the liver and reduce VOD risk in adults. [1]

How long do patients stay in the hospital after a transplant?

Usually several weeks, partly so the medical team can monitor for complications like VOD. [1]

What is the “preparative” phase of a transplant?

This is the same as the conditioning phase, where the patient receives chemo or radiation. [1]

Can VOD cause permanent liver damage?

If severe and not treated promptly, it can lead to permanent scarring or liver failure. [1]

Is jaundice always a sign of VOD?

While a common sign, jaundice can have other causes after a transplant, such as GvHD or infection. [1]

What is a TIPS procedure?

It is a stent placed in the liver to create a new path for blood flow and reduce pressure in the veins. [1]

Are some chemo drugs riskier than others for VOD?

Yes, drugs like gemtuzumab and inotuzumab are specifically linked to a higher risk of VOD. [1]

Does a history of liver disease matter?

Yes, having liver issues before a transplant significantly increases the risk of VOD. [1]

Can VOD cause kidney failure?

Yes, multi-organ dysfunction syndrome (MODS) caused by VOD often involves the kidneys. [1]

What is “mild” VOD?

A version of the condition that typically resolves with supportive care like fluid management. [1]

How is defibrotide administered?

It is given as an intravenous (IV) infusion, usually every six hours. [1]

Can VOD occur months after a transplant?

While most cases happen within 21 days, “late-onset” VOD can occur after the three-week mark. [1]

What is the first lab sign of VOD?

A drop in platelet counts that does not respond to transfusions is often the first sign. [1]

Why is salt intake restricted in VOD?

Salt causes the body to hold onto more water, which worsens the fluid buildup in the abdomen. [1]

Is a liver transplant common for VOD?

No, it is a last-resort option for severe cases where the liver has completely failed. [1]

What is “sinusoidal endothelial cell” damage?

It is the damage to the specific cells that line the liver's blood vessels, which triggers VOD. [1]

Can radiation therapy cause VOD?

Yes, high-dose total body irradiation (TBI) used in transplant conditioning is a known cause. [1]

What is the grading system for VOD?

It is a way for doctors to categorize how sick a patient is based on their symptoms and lab results. [1]

Does VOD affect blood clotting?

Yes, liver dysfunction can interfere with the body's ability to produce clotting factors. [1]

Is VOD more common in children?

Infants are at the highest risk, but it affects both pediatric and adult transplant patients. [1]

What is “portal hypertension” in VOD?

It is high blood pressure in the main vein that carries blood to the liver, caused by vessel blockages. [1]

Can VOD cause shortness of breath?

Yes, if fluid builds up around the lungs or if the heart is strained by the condition. [1]

How do doctors monitor for VOD?

Through daily weigh-ins, abdominal measurements, and frequent blood tests. [1]

What is “supportive care”?

Treatments aimed at managing symptoms, such as managing fluids, nutrition, and pain. [1]

Can VOD be treated at home?

No, it is a serious condition that requires intensive monitoring and IV treatments in a hospital. [1]

What is the FDA's role in VOD?

The FDA approves medications like defibrotide after reviewing clinical evidence of their safety and efficacy. [1]

Should I be worried about VOD before a transplant?

It is a serious risk, but your transplant team will take extensive precautions to minimize the danger. [1]

Further Reading

• Mohty M, Malard F, Alaskar AS, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a refined classification from the European society for blood and marrow transplantation (EBMT). Bone Marrow Transplant. 2023;58(7):749-754. PMID: 37095231.

Related Reading

Stem Cell Transplant (Bone Marrow Transplant): Types, Risks, and Recovery explains the transplant treatment during which VOD most often develops.

What Is Budd-Chiari Syndrome? Symptoms, Causes, and Treatment Options covers a related blockage of the large liver veins.

Ascites: Fluid Buildup in the Belly — Causes, Symptoms, Grades, Diagnosis & Treatment (Complete Guide) explains belly fluid buildup, a key sign of VOD.

Portal Hypertension: Complete Guide to Symptoms, Causes, Diagnosis, and Treatment describes high pressure in the liver's blood vessels and its complications.

Sources

1. Cleveland Clinic. Hepatic Veno-Occlusive Disease. Cleveland Clinic. Last updated March 4, 2026. https://my.clevelandclinic.org/health/diseases/hepatic-veno-occlusive-disease

2. Cheuk DKL, Chiang AKS, Ha SY, et al. Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2015;(5):CD009311. PMID 26017019. https://doi.org/10.1002/14651858.CD009311.pub2

3. Corbacioglu S, Topaloglu O, Aggarwal S. A Systematic Review and Meta-Analysis of Studies of Defibrotide Prophylaxis for Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome. Clin Drug Investig. 2022;42(6):465-476. PMID 35594010. https://doi.org/10.1007/s40261-022-01140-y

4. Sousa-Pimenta M, Martins Â, Estevinho LM, et al. Hepatic Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) Primary Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Network Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2024;13(22):6917. PMID 39598060. https://doi.org/10.3390/jcm13226917

Disclaimer

The information provided in this article is for educational purposes only and should not be considered medical advice. Always consult with your transplant team regarding any post-procedure symptoms.