Hepatic sinusoidal obstruction syndrome is caused by endothelial injury, leading to nonthrombotic occlusion of the terminal hepatic venules and hepatic sinusoids, rather than of the hepatic veins or inferior vena cava (as in Budd-Chiari syndrome).
(See also Overview of Vascular Disorders of the Liver.)
Venous congestion causes portal hypertension and ischemic necrosis (which leads to cirrhosis).
Etiology of Sinusoidal Obstruction Syndrome
Common causes include
Irradiation
Graft-vs-host disease resulting from bone marrow or hematopoietic cell transplantation
Pyrrolizidine alkaloids in crotalaria and senecio plants (eg, medicinal bush teas) and other herbs (eg, comfrey)
Other hepatotoxins (eg, dimethylnitrosamine, aflatoxin, azathioprine, some anticancer drugs)
Цінні поради та підводні камені
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Symptoms and Signs of Sinusoidal Obstruction Syndrome
Initial manifestations include sudden jaundice, ascites, and tender, smooth hepatomegaly. Onset is within the first 3 weeks of transplantation in bone marrow or hematopoietic cell recipients, who either recover spontaneously within a few weeks (or sometimes, with mild cases, after an increase in immunosuppressant therapy) or die of fulminant liver failure. Other patients have recurrent ascites, portal hypertension, splenomegaly, and, eventually, cirrhosis.
Diagnosis of Sinusoidal Obstruction Syndrome
Clinical evaluation and liver tests
Ultrasonography
Sometimes invasive tests (eg, liver biopsy, measurement of portal-hepatic venous pressure gradient)
The diagnosis is suspected in patients with unexplained clinical or laboratory evidence of liver disease, particularly in those with known risk factors, such as bone marrow or hematopoietic cell transplantation.
Laboratory results are nonspecific: elevated aminotransferase and conjugated bilirubin levels. Prothrombin time/international normalized ratio (PT/INR) becomes abnormal when disease is severe. Ultrasonography shows retrograde flow in the portal vein.
If the diagnosis is unclear, liver biopsy and measurement of the portal-hepatic venous pressure gradient is definitive (a pressure gradient > 10 mm Hg is consistent with sinusoidal obstruction syndrome). Measuring the pressure across the liver entails inserting a catheter percutaneously into a hepatic vein and then wedging it into the liver. This wedged pressure reflects portal vein pressure. (An exception is portal vein thrombosis; in this case, the pressure is normal despite portal hypertension.)
Treatment of Sinusoidal Obstruction Syndrome
Supportive care
Treatment of cause
For progressive disease, transjugular intrahepatic portosystemic shunting or transplantation
Ursodeoxycholic acid helps prevent graft-vs-host disease in bone marrow or hematopoietic stem cell transplant recipients.
Management includes withdrawing the causative agent (such as herbal teas) and providing supportive therapy. Defibrotide, a sodium salt of single-stranded oligodeoxyribonucleotide, has been demonstrated to protect endothelial cells from further activation, and may be considered in patients with sinusoidal obstruction syndrome that complicates hematopoietic stem cell transplantation (1).
Most patients have mild to moderate disease and do quite well. Transjugular intrahepatic portosystemic shunting (TIPS) can be tried for relief of portal hypertension, but has not yet been shown to prolong survival, particularly when sinusoidal obstruction syndrome is severe. In 25%, sinusoidal obstruction syndrome is severe, accompanied by fulminant liver failure. Liver transplantation is a last resort in highly selected patients.
Довідковий матеріал щодо лікування
1. Richardson PG, Riches ML, Kernan NA, et al: Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood 27(13):1656-1665, 2016. doi: 10.1182/blood-2015-10-676924
