Comprehensive analysis of transient elastography, ultrasonography, and blood biomarkers in SOS diagnosis and prediction

Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication following allogeneic hematopoietic cell transplantation (allo-HCT). The Seattle and Baltimore criteria are widely used for diagnosing SOS, but both have limitations in terms of sensitivity and positive predictive value. While liver biopsy provides definitive evidence, it carries a high risk of hemorrhage, prompting the need for less invasive diagnostic methods. Recently, non-invasive tests, including abdominal ultrasound (AUS) and liver stiffness measurement using transient elastography (TE), and several blood biomarkers such as procollagen III peptide (P3P) and plasminogen activator inhibitor 1 (PAI-1) have been reported for the diagnosis and prediction of SOS, though their applicability in different settings remains unclear due to insufficient validation. To date, there are no studies comparing the diagnostic utility of AUS, TE, and blood biomarkers in a single cohort of allo-HCT patients. Further research is needed to refine diagnostic approaches and improve patient outcomes. The aim of this prospective study was to comprehensively and quantitatively evaluate the diagnostic and predictive utility of these markers for SOS, using a stringent definition of SOS primarily based on histopathological confirmation through liver biopsy or autopsy. In a prospective study of 180 patients undergoing allo-HCT, we evaluated the diagnostic and predictive utility of liver stiffness measured by transient elastography (TE), abdominal ultrasound, and various blood biomarkers. Univariable logistic regression and area under the receiver operating characteristics curve (AUC) analyses were used to assess the significance of these measures. Out of 180 patients, 10 developed definitive SOS, most of which were based on pathological diagnosis. In the 48 patients who developed post-transplant liver injury, the AUC analysis highlighted that PAI-1 and liver stiffness were especially significant diagnostic markers for SOS, with highest AUCs of 0.85 (95% CI: 0.67–1.00) and 0.83 (95% CI: 0.67–0.98), respectively. Combining these markers resulted in an excellent diagnostic AUC of 0.96 (95% CI: 0.88–1.00). For predicting SOS in the 180 patients, pre-transplant P3P and liver stiffness were especially significant, with the highest AUCs of 0.82 (95% CI: 0.67–0.97) and 0.80 (95% CI: 0.61–0.99), respectively. Kinetic analysis showed that liver stiffness, PAI-1, and P3P levels increased throughout the early period after allo-HCT only in patients who developed SOS. Liver stiffness, PAI-1, and P3P are valuable markers for diagnosing and predicting SOS after allo-HCT. The combination of them offers excellent diagnostic and predictive accuracy, suggesting these markers should be integrated into clinical practice for better management of SOS in allo-HCT patients.