Treatment and prevention of hepatic sinusoidal obstruction syndrome following hematopoietic cell transplantation
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
Hepatic sinusoidal obstruction syndrome (SOS), previously termed hepatic veno-occlusive disease (VOD), is one of the most feared complications of allogeneic and autologous hematopoietic cell transplantation (HCT). It accounts for a significant fraction of transplant-related mortality and, in its severe form, is almost always fatal.
SOS is characterized by hepatomegaly, right upper quadrant pain, jaundice, and ascites, most often occurring in patients undergoing HCT and less commonly following the use of chemotherapeutic agents in non-transplant settings, ingestion of alkaloid toxins, after high dose radiation therapy, or liver transplantation. The disease resembles the Budd-Chiari syndrome clinically; however, hepatic venous outflow obstruction in SOS is due to occlusion of the terminal hepatic venules and hepatic sinusoids rather than the hepatic veins and inferior vena cava.
The prevention and management of hepatic SOS following HCT will be reviewed here. The pathogenesis, clinical features, and diagnosis of SOS following HCT are discussed separately. (See "Diagnosis of hepatic sinusoidal obstruction syndrome (veno-occlusive disease) following hematopoietic cell transplantation".)
Certain pretransplant characteristics and factors related to the transplant process are associated with the development of sinusoidal obstruction syndrome (SOS). The strength of these associations varies among studies, and no factor alone or in combination explains the variability in the risk of developing SOS among patients (table 1).
Pretransplant characteristics that are associated with an increased risk of SOS include preexisting liver disease (elevated serum aspartate aminotransferase, AST), younger patient age (higher rate in children <7 years), and poor baseline performance status. Proposed risk factors related to the transplant process include the source of graft (allogeneic greater than autologous), choice of conditioning therapy (higher with cyclophosphamide and high doses of radiation, lower with reduced intensity regimens), choice of graft-versus-host disease prophylaxis (use of sirolimus in combination with certain preparative regimens), and the use of specific antimicrobials (eg, vancomycin, amphotericin, acyclovir) prior to transplantation. These are described in more detail separately. (See "Diagnosis of hepatic sinusoidal obstruction syndrome (veno-occlusive disease) following hematopoietic cell transplantation", section on 'Overview'.)
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- Minimizing risk factors
- - Choice of agent
- - Ursodeoxycholic acid
- - Heparin
- - Defibrotide
- Assessing severity
- Supportive care
- Management of severe disease
- - Defibrotide
- - Transjugular intrahepatic portosystemic stent-shunt
- - Liver transplantation
- CLINICAL TRIALS
- SUMMARY AND RECOMMENDATIONS