Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation.

Sinusoidal obstruction syndrome (SOS), previously known as hepatic veno-occlusive disease (VOD), remains a multi-organ system complication following haematopoietic cell transplantation (HCT). When SOS/VOD is accompanied by multi-organ dysfunction, overall mortality rates remain >80%. However, the definitions related to the diagnosis and grading of SOS/VOD after HCT are almost 25 years old and require new and contemporary modifications. Importantly, the pathophysiology of SOS/VOD, including the contribution of dysregulated inflammatory and coagulation cascades as well as the critical importance of liver and vascular derived endothelial dysfunction, have been elucidated. Here we summarise new information on pathogenesis of SOS/VOD; identify modifiable and unmodifiable risk factors for disease development; propose novel, contemporary and panel opinion-based diagnostic criteria and an innovative organ-based method of SOS/VOD grading classification; and review current approaches for prophylaxis and treatment of SOS/VOD. This review will hopefully illuminate pathways responsible for drug-induced liver injury and manifestations of disease, sharpen awareness of risk for disease development and enhance the timely and correct diagnosis of SOS/VOD post-HCT.

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation.

The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.

Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD), increasingly referred to as sinusoidal obstruction syndrome, is a well-recognized complication of hematopoietic stem cell transplantation and contributes to considerable morbidity and mortality. In the Western Hemisphere, VOD, classified as a conditioning-related toxicity, is most commonly caused by stem cell transplantation. VOD has been described after all types of stem cell transplantation, irrespective of the stem cell source, type of conditioning therapy, or underlying disease. Recognition of this disease in the posttransplantation setting remains a challenge in the absence of specific diagnostic features because many other more common conditions can mimic it. Limited therapeutic or preventive strategies are currently available for the management of VOD. In this review, we provide a comprehensive account of the pathophysiology of this disease as we understand it today, risk factors for its development, and the current state of knowledge regarding preventive and therapeutic options.

Classification of hepatic venous outflow obstruction: ambiguous terminology of the Budd-Chiari syndrome.

Severe hepatic venous outflow obstruction and its manifestations often are recorded under the label "Budd-Chiari syndrome." Unfortunately, this label is ambiguous; it does not clearly identify the site of the lesion (hepatic veins versus inferior vena cava), its morphologic features (thrombotic versus nonthrombotic), or its cause. In the literature, implied or expressed definitions vary. Use of a standardized topographic and pathogenetic classification of hepatic venous outflow obstruction would enable investigators to group patients with comparable conditions, as required for therapeutic trials, prognostic evaluations, and studies of pathogenetic pathways. Review of our own cases revealed that hepatic venous outflow obstruction involving large hepatic veins is usually thrombotic and that isolated obstruction of the inferior vena cava or of small hepatic veins is usually nonthrombotic. Application of such a classification seems feasible and may yield useful results.

The clinical picture of veno-occlusive disease of the liver in Jamaican children

A study was made of 11 children suffering from "veno-occlusive disease of the liver" (V.O.D.). Clinically the disease was characterized by three overlapping phases, from the acute stage, with the sudden onset of hepatomegaly, with or without ascites, usually in infants from 18 months to three years of age, to the chronic stage, with the development of frank cirrhosis in later childhood. An attempt is made to outline the clinical natural history of V.O.D., as suggested by present information. The histology of V.O.D. is considered in outline. The primary lesion is a wide-spread occlusion of the smaller branches of the hepatic vein, the result of a primary endo-phlebitis; this is followed by the development of a non-portal type of cirrhosis radiating out from the central veins. The aetiology of V.O.D. is unknown, but it does not appear to be primarily or entirely nutritional; affected children are usually apparently adequately nourished. The possibility that V.O.D. is produced by the action of toxins, either bacterial or chemical, is considered, with special reference to "bush teas," which are widely used in Jamaica. Points of similarity are discussed between V.O.D. and serous hepatosis, Chiari's syndrome, senecio poisoning and Indian infantile cirrhosis (Summary)