From the Guidelines
Veno-Occlusive Disease (VOD) is a hepatic complication characterized by sinusoidal obstruction, leading to centrilobular hepatocellular necrosis and potentially severe liver damage.
Definition and Pathophysiology
- VOD, also known as Sinusoidal Obstruction Syndrome (SOS), is caused by injury to the sinusoidal endothelial cells, resulting in cell detachment, embolization, and sloughing towards central zones of hepatic lobules, leading to sinusoidal congestive obstruction [ 1 ].
- This obstruction can cause various degrees of centrilobular hepatocellular necrosis, and may be associated with other lesions such as centrilobular perisinusoidal and endovenular fibrosis, peliosis, and nodular regenerative hyperplasia (NRH) [ 1 ].
Clinical Presentation and Diagnosis
- The clinical presentation of VOD/SOS can range from mild liver test abnormalities to abdominal swelling and pain, ascites, hepatomegaly, and splenomegaly [ 2 ].
- Diagnosis is challenging due to the lack of specific clinical signs or serological diagnostic tools, and is often based on a high index of clinical suspicion, after exclusion of other potential mimicking causes [ 3 ].
- Transjugular liver biopsy combined with measurement of the wedged hepatic venous pressure gradient can be helpful in confirming the diagnosis [ 3 ].
Causes and Risk Factors
- VOD/SOS is a well-established hepatic complication of myeloablative regimens used in the setting of haematopoietic stem cell transplantation (HSCT) [ 1 ].
- Other risk factors include certain chemotherapeutic agents, immunosuppressors, total body or hepatic irradiation, and platelet transfusion containing ABO-incompatible plasma [ 1 ].
Treatment and Management
- Treatment of VOD/SOS relies mostly on supportive care, with therapy aimed at managing fluid retention, sepsis, and organ failure [ 3 ].
- Defibrotide has demonstrated a benefit for SOS prophylaxis in a randomized study in pediatric HSCT [ 3 ].
- Liver transplantation may be considered in severe cases, but is limited by the underlying malignancy and should be proposed only to patients with favorable oncologic prognosis or non-oncologic etiology [ 3 ].
From the Research
Definition and Characteristics of Veno-Occlusive Disease (VOD)
- Veno-Occlusive Disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) 4, 5, 6, 7, 8.
- It is characterized by hepatomegaly, right-upper quadrant pain, jaundice, and ascites, occurring after high-dose chemotherapy, HSCT, and less commonly, other conditions 5.
- The injury of the sinusoidal endothelial cells with loss of wall integrity and sinusoidal obstruction is the basis of development of postsinusoidal portal hypertension responsible for the clinical syndrome 5.
Clinical Presentation and Diagnosis
- Patients with VOD present with right upper-quadrant abdominal pain, jaundice, weight gain, and conjugated hyperbilirubinemia 4.
- The diagnosis of VOD has evolved to include the use of ultrasound, elastography, cross-sectional imaging, and image-guided biopsy, alongside clinical symptoms 4.
- The European Society for Blood and Marrow Transplantation criteria are used to diagnose VOD/SOS 7, 8.
Treatment and Management
- Defibrotide is the only medication approved by the US Food and Drug Administration for the management of severe VOD/SOS after HSCT 7.
- Early diagnosis, prompt initiation of defibrotide, and minimization of dosing interruptions may be key to successful treatment of VOD/SOS 7.
- Treatment includes supportive care, intensive management, and specific drug therapy with defibrotide 5.
- Prophylaxis approaches are under investigation due to the severity of VOD, particularly in cases with associated multiorgan disease 5.