Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome

Abstract

Hepatic sinusoidal obstruction syndrome is frequently linked to high-dose chemotherapy/total-body irradiation in recipients of haematopoietic stem cell transplantation, long-term use of azathioprine after organ transplantation and other chemotherapeutic agents. The incidence of hepatic sinusoidal obstruction syndrome varies from 0% to 70%, and is decreasing. Disease risk is higher in patients with malignancies, hepatitis C virus infection, those who present late, when norethisterone is used to prevent menstruation, and when broad-spectrum antibiotics and antifungals are used during and after the conditioning therapy. Hepatic sinusoidal obstruction syndrome presents with tender hepatomegaly, hyperbilirubinaemia and ascites, and diagnosis is mainly clinical (Seattle and Baltimore Criteria). Imaging excludes biliary obstruction and malignancy, but cannot establish accurate diagnosis. Hepatic sinusoidal obstruction syndrome may be prevented by avoiding the highest risk regimens, using non-myelo-ablative regimens, and reducing total-body irradiation dose. Treatment is largely symptomatic and supportive, because 70-80% of patients recover spontaneously. Tissue plasminogen activator plus heparin improves outcome in <30% of cases. Defibrotide, a polydeoxyribonucleotide, is showing encouraging results. Transjugular intrahepatic porto-systemic shunt relieves ascites, but does not improve outcome. Liver transplantation may be an option in the absence of malignancy. Prognosis is variable and depends on disease severity, aetiology and associated conditions. Death is most commonly caused by renal or cardiopulmonary failure.