Hepatic Veno-Occlusive Disease

Hepatic veno-occlusive disease (VOD) is a serious liver condition that can happen after a stem cell transplant. A stem cell transplant can treat and sometimes cure blood cancers and blood disorders.

This condition is also called sinusoidal obstruction syndrome (SOS). It’s most common after an “allogeneic” stem cell transplant, where you get stem cells from a donor. It can happen when the chemotherapy and/or radiation treatments you receive before the transplant cause damage to liver cells. These therapies are called “conditioning” or “preparative” treatments. They’re necessary to prepare your body to get new stem cells by destroying the abnormal ones. This creates space for the new stem cells to set up shop and mature into healthy blood cells.

In VOD, these treatments can lead to a series of events that can result in organ dysfunction and failure. In some people, VOD can be fatal.

Healthcare providers know to watch out for this complication. This is why they often have people stay in the hospital for several weeks after a transplant. That way, they can provide care at the first sign of an issue.

Symptoms of veno-occlusive disease

Symptoms usually show up within the first three weeks after treatment. Most start around the 12-day mark. But symptoms may start after three weeks, too. Symptoms include:

• Pain in your upper right abdomen, where your liver is
• Signs of jaundice, like yellowing in your skin, the whites of your eyes and mucous membranes
• Signs of fluid build-up, like a swollen belly and sudden weight gain

Other symptoms may mean the condition is harming other organs as well. Shortness of breath and trouble breathing may be signs of heart or lung issues. Liver issues can also affect your brain. Signs may include confusion and trouble thinking.

Veno-occlusive disease causes

VOD happens when toxic effects from high-dose chemotherapy or radiation damage your liver. This most often happens as a part of conditioning treatment before a stem cell transplant. Rarely, it happens after cancer or liver tumor treatments unrelated to a stem cell transplant.

With VOD, the toxic substances damage the cells lining tiny blood vessels in your liver. They’re called sinusoidal endothelial cells.

The damaged cell lining in these vessels can allow fluids inside to leak out. Meanwhile, substances that don’t belong in these tiny vessels flow inside. The extra “traffic” narrows the pathway that your blood needs to make its way through your liver. This can lead to blockages. If the condition gets worse, it can lead to high blood pressure in the main vein in your liver.

The damaging effects can lead to liver failure. VOD can harm other major organs, too.

Risk factors

The overall risk of developing veno-occlusive disease is about 5 to 15 out of every 100 people who get a stem cell transplant. But there are lots of risk factors. Some increase the risk of VOD much more than others. Some can be changed, while others can’t. 

Risk factors include your:

• Age: VOD is more common in infants than in any other age group. With adults, the risk of VOD increases with age.
• Preexisting conditions: Having a prior history of liver disease is a risk factor in both children and adults. Other conditions that increase the risk vary in children and adults.
• Type of stem cell transplant: VOD is more common in allogeneic stem cell transplants. This kind involves getting stem cells from a donor.
• Prior treatment: Certain chemotherapy drugs used to treat leukemias (for example, gemtuzumab and inotuzumab) can increase the risk of VOD.
• Conditioning treatment: High-intensity chemotherapy or radiation may increase the risk of VOD.
• Preventive treatment: Some drug regimens that prevent graft-versus-host disease (GvHD) may increase your risk of VOD. GvHD is when your body attacks the donated stem cells.

How doctors diagnose this condition

Symptoms are usually what make healthcare providers suspect you have VOD. Once they suspect it, they’ll start treatment ASAP. They don’t wait for test results to confirm it because of how serious VOD is. Your care team will monitor you closely in the weeks after your transplant, while you’re in the hospital.

Common tests include regular:

• Physical exams: They’ll check your belly for signs of fluid buildup or an enlarged liver. They’ll ask about your symptoms. Your provider will also track how much fluid you take in versus how much you’re peeing out.
• Blood tests: You’ll need regular lab work to check your blood cell counts. Low platelets that don’t improve with treatment are often the first sign of VOD. They’ll also do tests to check your liver function and see how your blood is clotting.
• Imaging: An ultrasound is the most common imaging test used. Your provider will get images of your abdomen before and after the transplant. This helps them see changes, like blood flow issues.
• Liver biopsy: In adults, providers sometimes take a liver sample for testing. But this only happens if your provider decides it’s safe.

Grading

Healthcare providers consider things like your symptoms and test results to grade VOD. Grades are:

• Mild/moderate
• Severe/very severe

How is it treated?

Treatment depends on how severe your condition is.

VOD is most commonly treated in the hospital. You may only need supportive care if your condition is mild/moderate. If you’re retaining fluids, you may need to reduce fluids and salt intake. You may need to take water pills. Or your healthcare provider may give you a diuretic by IV to clear out excess fluid.

One of the main treatments for VOD is defibrotide. The U.S. Food and Drug Administration (FDA) has approved this to treat severe veno-occlusive disease. You’ll get it through an IV. Most people receive it every six hours until they no longer show signs of VOD. You may need this medicine for several weeks.

Other treatments are rarely used but may be an option in severe cases:

• Transjugular intrahepatic portosystemic stent-shunt (TIPS): A procedure that opens up blocked blood vessels
• Liver transplant: A possible option if an organ is available from a compatible donor

What can I expect if I have this condition?

Before defibrotide, about 8 in 10 adults with severe hepatic veno-occlusive disease died. But new treatments and better guidelines for managing this condition have improved survival rates. These improvements have reduced how often people develop VOD in the first place.

But VOD can still lead to organ damage and be fatal. About 3 to 6 out of 10 people with VOD get damage in more than one organ.

This is why healthcare providers assess your risk factors before doing a stem cell transplant. They go to great lengths to reduce every risk they can to keep VOD from happening.

Can this be prevented?

Not always. But your healthcare provider will take steps to reduce your risk.

Children may get defibrotide before the transplant to protect liver cells from damage. Adults may receive a medicine called ursodeoxycholic acid (ursodiol) to help protect their liver. Research shows that it may reduce the chance of VOD and other liver complications after a stem cell transplant.

Your provider will also:

• Treat conditions that increase your risk: You may need treatments for liver disease or other conditions that may make VOD more likely. You may need this before it’s safe for you to have a stem cell transplant.
• Weigh benefits vs. risks: Your provider will recommend drugs that are most likely to help without causing negative effects. They may time your transplant so that any high-risk cancer meds you’re taking have time to leave your system.