B-054 Potential of Autotaxin in the Early Diagnosis of Sinusoidal Obstruction Syndrome after Allogeneic Hematopoietic Cell Transplantation
Authors: Takemura K , Nakamae M , Okamura H , Sakatoku K , Ido K , Makuuchi Y , Kuno M , Takakuwa T , Hirose A , Nishimoto M , Nakashima Y , Koh H , Igarashi K , Kubota H , Hino M , Nakamae H 
Published: September 2023

Abstract

Background
Sinusoidal obstruction syndrome (SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Early intervention leads to a good prognosis, but it is often difficult to differentiate SOS from other hepatobiliary complications. Liver biopsy is the gold standard for diagnosing SOS, but it is difficult to perform invasive testing early in the transplant process, and no specific biomarker for SOS has been established. Autotaxin (ATX) is useful as a liver fibrosis marker, the serum levels of which are elevated by metabolic inhibition of liver sinusoidal endothelial cells. Considering the pathophysiology of SOS, which begins with injury of liver sinusoidal endothelial cells, serum ATX levels may be elevated early in the onset of SOS.

Methods
A retrospective study was conducted of 247 patients who had received allo-HCT, including 11 patients who developed SOS and met the EBMT criteria (male, 7; female, 4). Of 11 patients with SOS, 9 had pathologically proven SOS. The median time from allo-HCT to SOS diagnosis was 31 days (range, 8–141 days [male], 16–31 days [female]). This cohort included 39 patients with hepatobiliary complications without SOS (total bilirubin &gt; 2 mg/dL; male, 23; female, 16). Serum ATX levels were measured in stored samples before conditioning and at days 1, 3, 5, 7, 14, 28, 60, 90, 180, and 365 after allo-HCT by a two-site enzyme immunoassay with an AIA-2000 analyzer. The area under the receiver operating characteristic (AUROC) of serum ATX levels for the diagnosis of SOS was analyzed.

Results
We first investigated the variability of serum ATX levels during the allo-HCT period. Serum ATX levels fluctuated as follows: decreased on day 1, increased and peaked on days 7–14, and then decreased again on days 28–60. A variety of factors associated with allo-HCT such as the conditioning regimen and administration of steroids affected serum ATX levels. Serum ATX levels before and after allo-HCT tended to be higher in patients with SOS. In male patients, the AUROCs of serum ATX levels on day 3 after allo-HCT were 0.75 (in all patients; 95% confidence interval [95%CI], 0.49–1.00) and 0.75 (in patients with hepatobiliary complications; 95%CI, 0.48–1.00). In female patients, the AUROCs of serum ATX levels on day 14 after allo-HCT were 0.88 (in all patients; 95%CI, 0.77–0.98) and 0.94 (in patients with hepatobiliary complications; 95%CI, 0.82–1.00). These findings indicated that serum ATX levels before the diagnosis of SOS had a diagnostic capacity. In addition, focusing on severe SOS cases, three of six patients had serum ATX levels above the upper reference limit before conditioning (a total of 18 patients exceeded the upper reference limit in this cohort). Of the remaining three patients, two had elevated post-transplant ATX levels near or above the upper reference limit prior to diagnosis of SOS.

Conclusion
Although validation by further studies with larger numbers of SOS cases is needed, the serum ATX level may be a useful biomarker for early diagnosis of SOS after allo-HCT.