Title: Alpha-Fetoprotein and APRI as Predictive Markers for Patients with Type C Hepatitis B-
Related Acute-on-Chronic Liver Failure: A Retrospective Study
Version: 3 Date: 25 Oct 2023
Reviewer:  Iliana Mani
Reviewer's report:
Dear Editor,
This is a really interesting study in HBV-related acute-on-chronic liver failure, proposing a new
prognostic model, using commonly available biomarkers, for short term mortality in this difficult
to treat population. However, there are several limitations in its current form.
Major comments:
• The manuscript needs extensive editing for grammar and syntax errors.
• Authors should provide information about HBV-DNA levels in survivors and non-survivors
as well as about treatment they received (Table 1).
• Was there any difference in treatment status in survivors vs non survivors?
• Authors should clarify which variables they included in their multivariate analysis. Inclusion
of highly correlated variables such as NLR and white blood cells, APRI and PLTs, ALT, FIB-4
and PLTs, Age, ALT, AST, overfits model and no solid results can be drawn.
It would be of great interest if they also performed a univariate analysis of HBV-DNA levels as a
predictor of mortality [Lei JH et al.   Is HBV viral load at admission associated with development
of acute-on-chronic liver failure in patients with acute decompensation of chronic hepatitis B
related cirrhosis?. BMC Infect Dis 19, 363 (2019). https://doi.org/10.1186/s12879-019-3988-1 ]
• In addition to the above, authors should provide more information about the statistical methods
they applied to choose parameters for the development of their model, especially if multivariate
analysis was overfitted.
• Authors should mention as a major limitation the lack of a validation cohort, as this parameter
is of paramount importance in the development of a predictive model.
To conclude, except of the language errors, my main concern is the statistical analysis on which
development of the proposed model was based.
Minor comments:
Table 1. Please expand all the abbreviations used (Pre – Alb, NLR, MLR, HE, MELD, TACIA,
COSSH-ACLF II)
Title: Alpha-Fetoprotein and APRI as Predictive Markers for Patients with Type C Hepatitis B-
Related Acute-on-Chronic Liver Failure: A Retrospective Study
Version: 3 Date: 25 Oct 2023
Reviewer:  Iliana Mani
Reviewer's report:
Dear Editor,
This is a really interesting study in HBV-related acute-on-chronic liver failure, proposing a new
prognostic model, using commonly available biomarkers, for short term mortality in this difficult
to treat population. However, there are several limitations in its current form.
Major comments:
• The manuscript needs extensive editing for grammar and syntax errors.
• Authors should provide information about HBV-DNA levels in survivors and non-survivors
as well as about treatment they received (Table 1).
• Was there any difference in treatment status in survivors vs non survivors?
• Authors should clarify which variables they included in their multivariate analysis. Inclusion
of highly correlated variables such as NLR and white blood cells, APRI and PLTs, ALT, FIB-4
and PLTs, Age, ALT, AST, overfits model and no solid results can be drawn.
It would be of great interest if they also performed a univariate analysis of HBV-DNA levels as a
predictor of mortality [Lei JH et al.   Is HBV viral load at admission associated with development
of acute-on-chronic liver failure in patients with acute decompensation of chronic hepatitis B
related cirrhosis?. BMC Infect Dis 19, 363 (2019). https://doi.org/10.1186/s12879-019-3988-1 ]
• In addition to the above, authors should provide more information about the statistical methods
they applied to choose parameters for the development of their model, especially if multivariate
analysis was overfitted.
• Authors should mention as a major limitation the lack of a validation cohort, as this parameter
is of paramount importance in the development of a predictive model.
To conclude, except of the language errors, my main concern is the statistical analysis on which
development of the proposed model was based.
Minor comments:
Table 1. Please expand all the abbreviations used (Pre – Alb, NLR, MLR, HE, MELD, TACIA,
COSSH-ACLF II)
Please review this paper.
user
Title: Alpha-Fetoprotein and APRI as Predictive Markers for Patients with Type C Hepatitis B-
Related Acute-on-Chronic Liver Failure: A Retrospective Study
Version: 3 Date: 25 Oct 2023
Reviewer:  Iliana Mani
Reviewer's report:
Dear Editor,
This is a really interesting study in HBV-related acute-on-chronic liver failure, proposing a new
prognostic model, using commonly available biomarkers, for short term mortality in this difficult
to treat population. However, there are several limitations in its current form.
Major comments:
• The manuscript needs extensive editing for grammar and syntax errors.
• Authors should provide information about HBV-DNA levels in survivors and non-survivors
as well as about treatment they received (Table 1).
• Was there any difference in treatment status in survivors vs non survivors?
• Authors should clarify which variables they included in their multivariate analysis. Inclusion
of highly correlated variables such as NLR and white blood cells, APRI and PLTs, ALT, FIB-4
and PLTs, Age, ALT, AST, overfits model and no solid results can be drawn.
It would be of great interest if they also performed a univariate analysis of HBV-DNA levels as a
predictor of mortality [Lei JH et al.   Is HBV viral load at admission associated with development
of acute-on-chronic liver failure in patients with acute decompensation of chronic hepatitis B
related cirrhosis?. BMC Infect Dis 19, 363 (2019). https://doi.org/10.1186/s12879-019-3988-1 ]
• In addition to the above, authors should provide more information about the statistical methods
they applied to choose parameters for the development of their model, especially if multivariate
analysis was overfitted.
• Authors should mention as a major limitation the lack of a validation cohort, as this parameter
is of paramount importance in the development of a predictive model.
To conclude, except of the language errors, my main concern is the statistical analysis on which
development of the proposed model was based.
Minor comments:
Table 1. Please expand all the abbreviations used (Pre – Alb, NLR, MLR, HE, MELD, TACIA,
COSSH-ACLF II)
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