What is sinusoidal obstruction syndrome (SOS), also known as veno‑occlusive disease (VOD)?

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Last updated: September 17, 2026 • View editorial policy

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What is Sinusoidal Obstruction Syndrome?

Sinusoidal obstruction syndrome (SOS), previously called veno-occlusive disease (VOD), is a potentially life-threatening liver complication characterized by injury and detachment of sinusoidal endothelial cells, leading to sinusoidal congestion, hepatic outflow obstruction, and varying degrees of centrilobular hepatocellular necrosis. 1

Pathophysiology

The disease process begins with sinusoidal endothelial cell injury and denudation from the vessel wall. These damaged cells then embolize and slough toward the central zones of hepatic lobules, creating a sinusoidal congestive obstruction through outflow blockage. Depending on the severity and level of obstruction, this can progress to centrilobular hepatocellular necrosis. SOS may also present with associated lesions including centrilobular perisinusoidal and endovenular fibrosis, peliosis, and nodular regenerative hyperplasia (NRH). 1

Major Causes

The most common setting is as a complication of myeloablative regimens used in hematopoietic stem cell transplantation (HSCT), where incidence has declined from 50% historically to approximately 14% currently due to improved prophylaxis and modified conditioning regimens. 1

Other major causes include: 1

  • Chemotherapeutic agents: Actinomycin D, azathioprine, busulfan, carmustine, cytosine arabinoside, cyclophosphamide, dacarbazine, gemtuzumab-ozogamicin, melphalan, mercaptopurine, mitomycin, oxaliplatin, 6-mercaptopurine, 6-thioguanine
  • Immunosuppressors: Used in solid organ transplantation or inflammatory bowel disease
  • Radiation: Total body or high-dose hepatic irradiation
  • Toxins: Pyrrolizidine alkaloids, urethane, terbinafine, traditional herbal remedies
  • Other: Platelet transfusion containing ABO-incompatible plasma

Clinical Presentation

The classic triad consists of: 1

  • Weight gain due to fluid retention (with or without ascites)
  • Tender hepatomegaly
  • Jaundice

However, clinical presentation ranges from asymptomatic disease to severe multiorgan dysfunction leading to death. In HSCT patients receiving cyclophosphamide, onset typically occurs within the first 20 days, though timing varies with different regimens. 1

Severity Classification

SOS is subdivided into three forms based on clinical course: 1

  • Mild: Self-limiting disease not requiring treatment
  • Moderate: Resolving disease requiring treatment, particularly for fluid retention
  • Severe: Disease not resolving after day 100 despite treatment, potentially fatal

Prognosis and Mortality

Mortality at 100 days ranges from 9% in mild cases to nearly 100% in clinically severe SOS. 1 Death most commonly results from renal, cardiopulmonary, or liver failure. Major parameters predicting poor outcome include high serum bilirubin, significant weight gain, aminotransferase elevation, elevated hepatic venous pressure gradient, renal dysfunction, and multiorgan failure. 1

Special Context: Oxaliplatin-Related SOS

In patients receiving oxaliplatin chemotherapy for colorectal liver metastases before surgical resection, SOS is associated with decreased imaging detection of liver metastases, increased operative bleeding, and post-operative liver dysfunction or delayed liver regeneration. The timeframe for regression of SOS and associated lesions remains uncertain, with histological persistence documented even months after completing treatment. 1

Diagnostic Challenges

A critical pitfall is that standard diagnostic criteria may be unreliable in patients with altered portal circulation, such as those with pre-existing transjugular intrahepatic portosystemic shunts (TIPS), where the shunt can decompress the portal system and mask hallmark clinical signs until advanced liver failure occurs. 2 Clinicians must maintain high suspicion when biochemical abnormalities emerge in these patients, as prompt recognition remains critical for survival.

The 2023 EBMT refined classification now distinguishes between probable, clinical, and proven SOS/VOD at diagnosis, with severity grading based on multiorgan dysfunction using Sequential Organ Failure Assessment (SOFA) scores. 3

References

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.