Hepatic veno-occlusive disease (ORPHA:890)
A rare vascular liver disease characterized by toxic injury to the hepatic sinusoidal capillaries that leads to obstruction of the small hepatic veins and sinusoids. Clinical manifestations include painful hepatomegaly, jaundice, and fluid retention that manifests by weight gain, edemas, and ascites.
Epidemiology
Prevalence is difficult to estimate as the frequency varies according to the underlying cause. The incidence due to pyrrolizidine alkaloid plant exposure is unknown, although in Ethiopia it has been estimated at 29.6/mill/year. In addition, epidemics may occur due to harvest contamination with these plants. Hepatic veno-occlusive disease (HVOD) develops in between 0. 3- 2.3% of patients who receive liver transplant; in up to 15% of those treated with gemtuzumab ozogamicin (GO); and in 2-15% of those who receive hematopoietic stem cell transplantation (HSCT), rising to 40% in patients with a history of GO treatment.
Clinical description
It affects children and adults. The clinical picture is characterized by painful hepatomegaly, jaundice, and fluid retention that manifests by weight gain, edemas, and ascites. Hepatic insufficiency manifesting as jaundice, and hepatic encephalopathy may occur. Functional renal insufficiency is common. In severe cases, multiple organ failure or severe bacterial infections may occur. In developed countries, the disease is mainly associated with the conditioning regimen for HSCT, with currently less than 10% of transplant patients (depending on the conditioning regimen protocol used) developing HVOD. HVOD may also occur after chemotherapy or radiation therapy.
Etiology
Hepatic sinusoidal endothelial cell lesions appear to be the primary cause of the disease, leading to non-thrombotic occlusion of hepatic veins with concentric subendothelial thickening associated with edema and eventually fibrosis.
Diagnostic methods
Diagnosis is based on recognition of the clinical manifestations (hepatomegaly, jaundice, and weight gain) and their association with a potential cause of HVOD (HSCT or chemotherapy, exposure to pyrrolizidine alkaloids), together with exclusion of other causes of liver disease. Liver biopsy is often indicated, and recent data support its indication. Imaging studies, particularly hepatic Doppler-ultrasonography, may help to confirm the diagnosis.
Differential diagnosis
Differential diagnoses include other causes of acute or chronic liver disease, and, in the case of HSCT, graft-versus-host disease and severe infections.
Management and treatment
No specific treatment is available. Defibrotide is recommended for severe sinusoidal obstruction syndrome, mainly on the basis of limited studies (historic comparisons) and because side effects are uncommon. Management is with supportive care (nutritional support, intensive care unit if needed for respiratory or renal support), renal function monitoring, and avoidance of other liver drug toxicity. Preventive treatment with ursodeoxycholic acid is indicated from beginning of conditioning to 90 days post-transplantation. In case of HSCT, the risk of disease is managed prophylactically by the characterization of risk factors prior to transplantation. Liver transplantation should be discussed in patients with excellent hematologic prognosis.
Prognosis
Severity and course of the disease varies between patients. In severe cases, the prognosis is poor with a high mortality rate (up to 90%) due to multiple organ failure.

                            Last update: 
                            December 2021


                            - Expert reviewer(s): 
                            Dr Aurélie PLESSIER | RARE-LIVER*


                                * European Reference Network