Liver Stiffness Measurement Allows Early Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Adult Patients Who Undergo Hematopoietic Stem Cell Transplantation: Results from a Monocentric Prospective Study

Abstract

A B S T R A C T Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complication affecting patients undergoing hematopoietic stem cell transplantation (HSCT). The survival rate is higher when specific therapy is initiated early; thus, improving early, noninvasive diagnosis of VOD/SOS is an important need. In an adult population undergoing HSCT, we aimed to assess the role of liver stiffness measurement (LSM), evaluated by transient elastography (TE), for diagnosing VOD/SOS. Between April 2016 and March 2018, 78 consecutive adult patients with indications for allogeneic HSCT were prospectively included. LSM was performed before HSCT and at days +9/10, +15/17, and +22/24 post-HSCT. New European Society for Blood and Marrow Transplantation criteria were used to establish VOD/SOS diagnosis. Four patients developed VOD/SOS (5.1%) during the study period, with a median time of +17 days post-HSCT. A sudden increase in LSM compared with previously assessed values and pre-HSCT values, was seen in all patients who developed VOD/SOS. LSM increases occurred from 2 to 12 days before clinical SOS/VOD appearance. The VOD/SOS diagnostic performance of increased LSM over pre-HSCT assessment showed an area under the receiver operating characteristic curve of 0.997 (sensitivity 75%; specificity 98.7%). LSM gradually decreased following successful VOD/SOS-specific treatment. Interestingly, LSM values did not increase significantly in patients experiencing hepatobiliary complications (according to the Common Terminology Criteria) other than VOD/SOS. LSM by TE can be considered a promising method to perform an early, preclinical diagnosis and follow-up of VOD/SOS.

Longitudinal evaluation of liver stiffness in three pediatric patients with veno‐occlusive disease

“…In addition, Colecchia et al first and Reddivalla et al subsequently have demonstrated that LSM, using TE and two‐dimensional SWE, respectively, had a sudden increase up to more than a week before the diagnosis of VOD/SOS in pediatric patients. Recently, the same findings have been demonstrated in a monocentric cohort of 78 adult patients …”

“…Although these three cases are homogenous in terms of transplant characteristics, they are not exhaustive and additional data are needed to confirm our observation that LSM may be a useful tool able to predict the clinical evolution of VOD under treatment, anticipating the improvement of clinical and laboratory signs of VOD/SOS. Furthermore, it would be really interesting to evaluate in pediatric patients the potential role of liver stiffness in the differential diagnosis between VOD/SOS and other hepatic complications (drug toxicity, acute GVHD), as recently evaluated in adults and to follow patients who did not have a good recovery after the treatment.…”

“…The correlation between the changes of the stiffness and VOD/SOS can be due to its pathogenesis, which is characterized adults 13 and to follow patients who did not have a good recovery after the treatment.…”

“…Recently, the same findings have been demonstrated in a monocentric cohort of 78 adult patients. 13 The aim of our study was to evaluate the liver stiffness before and at least three times (once every seven days after the transplant) with particular attention to patients who developed VOD/SOS, in order to record its value at the moment of diagnosis and its variation during the period of treatment. 14,15…”

Diagnosis and Treatment of VOD/SOS After Allogeneic Hematopoietic Stem Cell Transplantation

“…In HSCT patients, LSMs were carried out at baseline and once a week after HSCT. Only in patients who developed VOD/SOS, LSM values markedly increased compared to previous measurement (from 10.3-59.3 vs. 3.5-7.5 kPa) (62,63). Liver stiffness measurement increases from 1 to 15 days before clinical VOD/SOS diagnosis and most intriguingly LSM decreased after the start of defibrotide treatment parallel to clinical signs of VOD/SOS (e.g., bilirubin, weight) (63)(64)(65)(66)(67)(68)(69).…”