## 4 Discussion  
Although various diagnostic criteria have been published [17; 19; 21; 33; 34] the diagnosis of SOS is still challenging. SOS remains a clinical diagnosis until proven by biopsy. For a long time, ultrasound examinations have been used to rule out SOS rather than to confirm its presence [24]. Nevertheless, novel scoring systems have been developed to diagnose SOS by ultrasound including a selection of 10 sonographic parameters (HOKUS-10) [29]. These parameters have been refined recently [35] and the diagnosis of SOS by ultrasound was called \"confirmed\" when ascites was present and two of the following six findings were detected at the same time: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase [35]. In summary, standardized ultrasound protocols for SOS investigation may help to facilitate diagnosis. We included laboratory as well as ultrasound values and present the first study to incorporate all published parameters into a comprehensive SOS ultrasound protocol. In our study population of 23 patients, no case of SOS was detected, but we observed significant changes in laboratory parameters comparing them pre- and post-alloHSCT. Results from this study showed a significant increase in bilirubin levels after allogeneic transplantation, which may be explained in part by the design of our study protocol, in which patients were scheduled for a second ultrasound evaluation when their bilirubin level rose or when their timeline approached day 21 following transplantation. Few patients without bilirubin increase or clinical suspicion of SOS missed their second ultrasound examination and needed to be excluded from the analysis, which leads to a slight tilt of the study population. Other reasons for hyperbilirubin besides SOS (where a bilirubin level greater than 2 mg/dL is a diagnostic criterion [33]) have to be taken into account, such as toxic effects of the conditioning regimen and other drug toxicities, e.g., anti-thymocyte-globulin-induced hyperbilirubinemia [34; 35; 36]. In this study, 65.21% (15 out of 23) of the enrolled patients received anti-thymocyte-globulin (ATG), which may have contributed to increased bilirubin levels in our cohort. However, as bilirubin series as a diagnostic criterion for SOS, we kept this parameter as part of the protocol. The reasonability of this approach is emphasized by results of a recent study that reported a correlation between early bilirubinemia (cut off defined at 3.6 mg/dL) and increased non-relapse mortality independent of SOS [37]. Again, this fact may highlight the importance to monitor bilirubin levels with caution. Other changes in laboratory parameters observed in our study may also be explained by transplant-related side effects. For example, application of ATG or transplant-related infections may contribute to increased CRP levels as observed in our population [38]. Patients in our study had a median thrombocyte count of 24 G/L at the day of their ultrasound examination after alloHST, which was markedly decreased compared to values before transplantation, owing mostly to the conditioning regimen and aplasia that is prevalent following alloHST. Even though clinical separation from thrombocytopenia related to other reasons can be tough, increased consumption of thrombocytes may be observed in SOS [22], and therefore we included platelet count evaluation in our protocol. In line with a previously published study [39], which described an elevation of the liver enzymes ALT and AST higher than grade 3 (according to CTCAE v5.0) to be very rare after alloHST, we observed even a decrease in the level of these enzymes in our cohort. Therefore, being less confounded by other factors, AST and ALT levels may serve as a favorable surrogate marker for liver damage in general and SOS specifically, provided that veno-occlusive disease is rather associated with increased ALT levels [22].