ELASTOVOD PROJECT: Prospective studies to evaluate the preclinical diagnostic potential of hepatic ultrasound-based elastography measurement for predicting the development of Sinusoidal Obstruction Syndrome (SOS/VOD) and hepatic complications in patients undergoing hematopoietic stem cell transplantation (HSCT)“

Veno-occlusive-disease(VOD),also known as sinusoidal-obstruction-syndrome(SOS), is one of the main complications of hematopoietic stem cell transplantation and is related to the treatment with pyrrolizidine alkaloids or other toxic agents. Clinical diagnosis using the new criteria is the reference for SOS/VOD diagnosis. Increasing evidence suggests the emerging role of several imaging methods that could help the clinician in VOD/SOS assessment. The survival rate is higher when earlier specific therapy is initiated,improving early, non-invasive diagnosis of SOS/VOD is strongly needed.We aimed to assess in patients undergoing HSCT, the SOS/VOD diagnostic role of Liver Stiffness Measurement (LSM) evaluated by elastography techniques. The ElastoVOD project was an interventional study without drugs developed in two sequential phases:the first was monocentric proof of the concept study in Bologna from April 2015 to November 2017; the second was a national multicentre study involving around 47 Italian transplant centres and is still ongoing (clinicaltrial.govNCT03426358). LSM was performed before HSCT and at day +9/10, +15/17 and +22/24 post-HSCT. EBMT-criteria were used to establish a VOD/SOS diagnosis. Among the 456 patients undergoing HSCT, 20 patients developed SOS/VOD (4.4%) during the study period. A sudden increase of LSM, compared to the previous assessment and pre- HSCT measurement, was found in all patients who developed SOS/VOD. LSM increases occurred from 1 to more than ten days before clinical SOS/VOD appearance. The SOS/VOD diagnostic performance of increased LSM over pre-HSCT assessment showed AUROC 0.997 (Sens.75%Spec.98.7%). LSM gradually decreased following successful SOS/VOD specific treatment. Interestingly in the adult patient’s subgroup, LSM values did not significantly increase in patients experiencing hepato-biliary complications other than SOS/VOD. Elastography techniques measuring LSM represent the most recent and promising approach to perform an early, pre-clinical diagnosis and follow-up of SOS/VOD. In our view, a multidisciplinary approach to the SOS/VOD diagnosis should be highly encouraged.