Hepatic venoocclusive disease

Synonyms

2

Overview

Hepatic veno-occlusive disease or veno-occlusive disease (VOD) or  Sinusoidal Obstruction Syndrome (SOS) is a condition in which some of the small veins in the liver are obstructed. It is 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 now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation.

Apart from chemotherapy, VOD may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids (in some herbal teas), and has been described as part of a rare hereditary disease called hepatic venoocclusive disease with immunodeficiency (which results from mutations in the gene coding for a protein called SP110).

Along with graft versus host disease (GVHD) and cytomegalovirus (CMV) infection, veno-occlusive disease (VOD) is one of the most frequently encountered serious complications after stem cell transplantation. The reported overall incidence rate of veno-occlusive disease ranges from 5% to more than 60% in children who have undergone stem cell transplantation, and similar rates have been reported in adults.

Symptoms

Signs and symptoms may include:

  • Abdominal swelling or stretching
  • Pain in the right upper abdomen
  • Vomiting blood
  • Yellowing of the skin (jaundice)
  • Weight gain
  • Tender hepatomegaly
  • Aascites
  • Increased bilirubin
  • It often is associated with renal failure

Causes

Hepatic vein obstruction prevents blood from flowing out of the liver and back to the heart. This blockage can cause liver damage. Obstruction of this vein can be caused by a tumor or growth pressing on the vessel, or by a clot in the vessel (hepatic vein thrombosis).

Most often, it is caused by conditions that make blood clots more likely to form, including:

  • Abnormal growth of cells in the bone marrow (myeloproliferative disorders)
  • Cancers
  • Chronic inflammatory or autoimmune diseases
  • Infections
  • Inherited (hereditary) or acquired problems with blood clotting
  • Oral contraceptives
  • Pregnancy

Hepatic vein obstruction is the most common cause of Budd-Chiari syndrome.

Prevention

The absence of effective therapies for VOD has spurred much interest in developing effective preventive strategies for the disease. Heparin is the best-studied agent used for prevention. Multiple studies have suggested that low-dose heparin can decrease the overall incidence of VOD, although its effect on the incidence of severe disease is unproved. In a large prospective randomized trial, administration of 100 U · kg–1 · d–1 of unfractionated heparin started 1 week before transplantation and continued until day 30 decreased the overall incidence of VOD by nearly 10%.100 Use of low-molecular-weight heparin in place of unfractionated heparin can decrease the risk of bleeding episodes and has the advantage of intermittent dosing. Low-molecular-weight heparin also may accelerate platelet engraftment, but the mechanism is unclear. Ursodeoxycholic acid is administered orally and is usually well tolerated. At least 2 prospective randomized studies have shown a decreased incidence of VOD with the prophylactic use of this agent; another study showed no additional benefit when ursodeoxycholic acid was combined with heparin. Low-dose PGE1, initiated before conditioning therapy and continued for 30 days after transplantation, decreased the incidence of VOD in a study involving patients with acute leukemia who received allogeneic transplants. However, other studies have been unable to re596 Hepatic Veno-occlusive Disease Mayo Clin Proc, May 2003, Vol 78 produce the results, and PGE1 use has been associated with considerable toxicity. Pentoxifylline, a xanthine derivative, has been studied in prospective trials based on initial results from small studies. Pentoxifylline is capable of preventing transcription of tumor necrosis factor α and stimulates endothelial production of PGI2 and PGE2. These trials showed no clinically meaningful benefits from the use of pentoxifylline, and its use was associated with adverse effects. Parenteral glutamine used prophylactically may decrease the incidence of VOD.

Diagnosis

One of the signs is swelling of the abdomen from fluid buildup (ascites). The liver is often swollen and tender.
Tests include:

  • CT (computer tomography) scan or MRI of the abdomen
  • Doppler ultrasound of the liver veins
  • Liver biopsy
  • Liver function tests
  • Ultrasound of the liver

Prognosis

When associated with bone marrow transplant, VOD is fatal in over 30% of cases. 

Severity and course of the disease vary between patients. In severe cases, the prognosis is poor with a high mortality rate (up to 90%) due to multiple organ failure.

The risk of veno-occlusive disease in the pediatric population is not limited to a well-defined group of high-risk patients who have undergone transplantation. The disease frequently occurs outside this group. For example, patients treated for solid tumors (eg, Wilms tumor, neuroblastomas, and rhabdomyosarcomas are at a high risk for developing veno-occlusive disease. It has also been described in a patient with Burkitt lymphoma.

Treatment

Treatment varies, depending on the cause of the blockage.

  • Blood-thinners (anticoagulants)
  • Clot-busting drugs (thrombolytic treatment)
  • Medicines to treat for the liver disease, including ascites

Defibrotide (Defitelio) is a single-stranded polydeoxyribonucleotide derived from porcine tissue that possesses antithrombotic, thrombolytic, anti-inflammatory, and anti-ischemic properties. In March 2016, the FDA approved defibrotide (Defitelio) for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT)
 

Surgery:

  • Angioplasty and stent placement
  • Liver transplant
  • Transjugular intrahepatic portosystemic shunt (TIPS)
  • Venous shunt surgery