(See also Overview of Vascular Disorders of the Liver.)
Venous congestion causes portal hypertension and ischemic necrosis (which leads to cirrhosis).
Etiology
Common causes include
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Irradiation
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Graft-vs-host disease resulting from bone marrow or hematopoietic cell transplantation
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Pyrrolizidine alkaloids in crotalaria and senecio plants (eg, medicinal bush teas) and other herbs (eg, comfrey)
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Other hepatotoxins (eg, dimethylnitrosamine, aflatoxin, azathioprine, some anticancer drugs)
Symptoms and Signs
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
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, invasive tests become necessary—eg, liver biopsy or measurement of the portal-hepatic venous pressure gradient (a pressure gradient > 10 mm Hg suggests 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
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.
Treatment reference
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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.
