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.

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

“…Iguchi et al observed increased serum levels of VEGF during development of SOS in human patients, 40 leaving open the question of whether VEGF-induced acceleration of vasopermeability, neovascularization, and/or expression of coagulopathic tissue factors on circulating mononuclear cells may play a role in SOS pathogenesis. 32 Nakamura et al 41 hypothesized that antiangiogenic agents may protect against SOS, and chose to use sorafenib to test this hypothesis. Sorafenib is a multiple receptor tyrosine kinase inhibitor that inhibits multiple tyrosine kinases including the VEGF receptor-2 (VEGFR-2) and -3 (VEGFR-3).…”

“…Key pathogenic factors include SEC glutathione depletion, nitric oxide depletion, increased expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. 32 In the first instance, drugs leading to SOS are metabolized exclusively by the hepatocellular cytochrome P450 systems, for which glutathione is an antioxidant recovery mechanism. Hepatic exposure to these drugs leads to depletion of glutathione.…”

Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

“…Abnormalities of liver function were generally transient and reversible. Veno-occlusive disease (VOD) occurred in seven patients (3%), of whom two patients deceased [12]. VOD is the most severe adverse event of GO.…”

Hepatobiliary Quiz Answers—19 (2016)

“…Other important factors are nitric oxide depletion, vasoconstriction, increased expression of matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor and activation of clotting cascade. [40][41][42][43] Increased expression and release of MMP9is an early change in the pathogenesis of SOS. MMP9 inhibitors have been found to prevent SOS in animal models.…”