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: 5 Date: 14 May 2024
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Overall the revised manuscript appears to address most of the key
issues raised in initial peer review.  This is a unique analysis addressing an issue of high
clinical relevance due to the high mortality associated with HBV-related acute-on-chronic
liver failure and contributes a novel risk model which is potentially actionable.  There are
intrinsic methodologic limitations which are not modifiable but should be addressed fully in the
discussion section.
ADDITIONAL REQUESTS/SUGGESTIONS:
1) study population: the additional language clarifying diagnostic criteria for HBV-ACLF is
helpful both in text and Figure 1, but it remains unclear how the investigators adjudicated
HBV as precipitant for ACLF versus other precipitants as well as distinction between ""further
decompensation"" as part of natural history of decompensated cirrhosis versus ACLF - please
kindly comment; 2) Results: please include oral NUC status in Table 1 - clinically we would
expect antiviral therapy to be associated with lower risk of hepatic decompensation and
improved transplant-free survival based on published data - please also comment on observations
on oral NUC in model in discussion section; 3) discussion: comment on significance of these
findings in context of existing data on type A and B HBV-ACLF; 4) discussion: would
suggest identifying homogenous population (Chinese) as potential limitation which may not be
applicable to other populations"
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: 5 Date: 14 May 2024
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Overall the revised manuscript appears to address most of the key
issues raised in initial peer review.  This is a unique analysis addressing an issue of high
clinical relevance due to the high mortality associated with HBV-related acute-on-chronic
liver failure and contributes a novel risk model which is potentially actionable.  There are
intrinsic methodologic limitations which are not modifiable but should be addressed fully in the
discussion section.
ADDITIONAL REQUESTS/SUGGESTIONS:
1) study population: the additional language clarifying diagnostic criteria for HBV-ACLF is
helpful both in text and Figure 1, but it remains unclear how the investigators adjudicated
HBV as precipitant for ACLF versus other precipitants as well as distinction between ""further
decompensation"" as part of natural history of decompensated cirrhosis versus ACLF - please
kindly comment; 2) Results: please include oral NUC status in Table 1 - clinically we would
expect antiviral therapy to be associated with lower risk of hepatic decompensation and
improved transplant-free survival based on published data - please also comment on observations
on oral NUC in model in discussion section; 3) discussion: comment on significance of these
findings in context of existing data on type A and B HBV-ACLF; 4) discussion: would
suggest identifying homogenous population (Chinese) as potential limitation which may not be
applicable to other populations"
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: 5 Date: 14 May 2024
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: Overall the revised manuscript appears to address most of the key
issues raised in initial peer review.  This is a unique analysis addressing an issue of high
clinical relevance due to the high mortality associated with HBV-related acute-on-chronic
liver failure and contributes a novel risk model which is potentially actionable.  There are
intrinsic methodologic limitations which are not modifiable but should be addressed fully in the
discussion section.
ADDITIONAL REQUESTS/SUGGESTIONS:
1) study population: the additional language clarifying diagnostic criteria for HBV-ACLF is
helpful both in text and Figure 1, but it remains unclear how the investigators adjudicated
HBV as precipitant for ACLF versus other precipitants as well as distinction between ""further
decompensation"" as part of natural history of decompensated cirrhosis versus ACLF - please
kindly comment; 2) Results: please include oral NUC status in Table 1 - clinically we would
expect antiviral therapy to be associated with lower risk of hepatic decompensation and
improved transplant-free survival based on published data - please also comment on observations
on oral NUC in model in discussion section; 3) discussion: comment on significance of these
findings in context of existing data on type A and B HBV-ACLF; 4) discussion: would
suggest identifying homogenous population (Chinese) as potential limitation which may not be
applicable to other populations"
assistant