Review for 10.1186/s12876-021-02007-w (2021)

Reviewer’s report
Title: 
A neutrophil-to-lymphocyte ratio-based prognostic model to predict
mortality in patients with HBV-related acute-on-chronic liver failure
Version: 
1 
Date: 
21 Jun 2021
Reviewer's report:
Sun and colleagues present a large cohort analysis assessing the biomarker
neutrophil lymphocyte ratio in a group of patients with hepatitis B related acute
on chronic liver failure. This allows a large comprehensive analysis and
interestingly since it uses the APASL definition not all patients have cirrhosis.
While it confirms what other authors have shown it is of interest that this is
suitable in the HBV ACLF population. Where I am unclear is what true
comparisons they have made to EASL Models and how this would actually
shape clinical practice. 
The replacement of lactate with NLR is interesting. 
Introduction 
I disagree that T lymphocytes are the primary driver of the failure to recover
after BI. There is substantial evidence on the role of the innate immune system in
ACLF and this should be mentioned and referenced. 
There is no evidence that artificial liver support improves outcomes in patients
with ACLF
Methods
How did the physicians diagnose cirrhosis - this is vital as this should align with
other similar studies. Saying this was done by 2 physicians is not enough
How was the "poorest" result defined if WBC were high or low? 
Was the most up to date MELD which includes Na used?
Was HCC an exclusion? Cancer has been shown to be a factor in elevated NLR
What form of artificial liver support was used and why and when? What were
the indications for its use and what were the outcomes?
Is liver transplant performed in patients with HBV ACLF in a protocolised
manner (ie what are the contraindications to proceeding in terms of levels of
organ support for example).
Results
In section 3.2 the authors say the performance of lactate was inferior. Inferior to
what? To NLR in predicting 28 or 90 day mortality? Please clarify
Did the authors compare the AUROC curves quantitatively? I am unclear that
while accurate if the novel score is more accurate than others. I suggest the
Hanley and McNeill method.
Why are there no CI on Fig 4 A? 
Showing the dots as well as the bars would be better for all of the bar graphs.
Discussion 
The ACLF microenvironment is a misnomer. Are the authors referring to the
hepatic microenvironment during ACLF or the peripheral compartment of
circulating immune cells?
When the authors say regulatory T cells do they mean Tregs? These are a highly
specialised subgroup and more could be said on more conventional subtypes.
It would be worth explaining the potential dynamic course of NLR - is admission
value the most optimal for prognositicaion?
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