Review for 10.1186/s12876-021-02006-x (2021)

Reviewer’s report
Title: 
Soluble Urokinase Plasminogen Activator Receptor is Associated with
Short-Term Mortality and Enhanced Reactive Oxygen Species Production in
Acute-on-Chronic Liver Failure
Version: 
0 
Date: 
22 Jan 2021
Reviewer's report:
The authors present a paper describing the relationship between suPAR and
short-term mortality of acute-chronic liver failure based on a prospective cohort
of 282 patients with ACLF from three hospitals in China. Several previous
publications have demonstrated the plasma suPAR levels predict poorer survival
and the severity of in some patients with infectious diseases, autoimmune
inflammation and tumors. The authors attempt to determine whether suPAR can
be used as a diagnostic tool for acute-chronic liver failure and discovered suPAR
enhanced neutrophil ROS production in patients with HBV-related ACLF.
The paper has several methodological flaws which appear to lead to a conclusion
not completely supported by the evidence.
1. The article demonstrates that suPAR is sssociated with short-term mortality of
acute-chronic liver failure and suPAR induces neutrophil ROS generation, but
there is a lack of discussion about the enhanced ROS production.
2. suPAR induces neutrophil ROS generation, and the amount of ROS
generation accumulates over time, whether or not to detect ROS production at
the same time during blood collection.
3. In the article, the author mentioned the application of suPAR to circulating
neutrophils and an enhanced ROS production, but it was not clarified in the
methodology and discussion section. In the discussion section of the article, the
relationship between ROS and suPAR should be discussed. 
4. When discussing suPAR is a suitable biomarker for short-term outcomes in
patients with ACLF and suggesting elevated serum suPAR levels promote
disease progress in HBV related-ACLF, but the mechanism of how it regulates
ROS production in neutrophils has not been explained.
5. In the article, the author mentioned there was enhanced ROS production after
suPAR addition, but there were no control group. What about non-HBV-related
ACLF patients or non-ACLF patients? Only six patients were tested for ROS
production, it seem that there were no significant difference in ROS production
before and after suPAR addition from the figure 4(b).
6. The article only mentioned that during the 30-day and 90-day follow-up, the
mortality rate was 22.0% and 29.1%, respectively. The median follow-up time
and median survival time should be shown in the results section.
7. The diagnostic efficiency of suPAR alone is not very high. Whether
combining other prognostic indicators such as MELD and CTP score can
improve the predictive value of short-term survival?
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
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Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes