Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 2 Date: 06 Dec 2021
Reviewer's report:
Many of my previously posed questions have been dealt with satisfactorily.
I would disagree with the comment that tissue cannot be used for diagnosis due to the risks
associated with biopsy and esp looking at the severity of disease esp in the ALF cohort (severity
of coagulopathy). TJ biopsy can be safely performed in ALF and coagulopathic patients; the
main problem is around sampling errors/diagnostic yield in case an area of necrosis is biopsied,
this may not be relevant in relation to SOD levels though.
Are there any animal experiments regarding tissue SOD levels in ALF? If so this should be
referenced.
In the  Methods and Result sections "HEV on the ground of ALD, CHB" should be changed  to
"on the background of ALD, CHB" and throughout the manuscript.
AUROC curves and levels should be provided for SOD, the area under the ROC curves don't
look as though there is a very specific and sensitive cutoff value which could be used as a
prognostic indicator, which is somewhat one of the main goals of the paper.
The definition of ALF in the Introduction is poor - page 3 last sentence; the same definition as
per the later quoted APASL criteria or other commonly used definitions should be used "Bernal
et Wendon NEJM Dec 2013".
Do the authors think that the SOD levels are predominantly linked to organ failure and given
the difference ACLF vs ALF. Were the decompensated ACLF patients sicker in terms of MOF
which would also explain the high mortality? Are SOFA scores or other organ failure scores
available?
In other words is SOD just a marker of organ failure and associated ROS activation, rather than
HEV specific - this could be briefly appraised  in the Discussion and as a possible confounder.
Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 2 Date: 06 Dec 2021
Reviewer's report:
Many of my previously posed questions have been dealt with satisfactorily.
I would disagree with the comment that tissue cannot be used for diagnosis due to the risks
associated with biopsy and esp looking at the severity of disease esp in the ALF cohort (severity
of coagulopathy). TJ biopsy can be safely performed in ALF and coagulopathic patients; the
main problem is around sampling errors/diagnostic yield in case an area of necrosis is biopsied,
this may not be relevant in relation to SOD levels though.
Are there any animal experiments regarding tissue SOD levels in ALF? If so this should be
referenced.
In the  Methods and Result sections "HEV on the ground of ALD, CHB" should be changed  to
"on the background of ALD, CHB" and throughout the manuscript.
AUROC curves and levels should be provided for SOD, the area under the ROC curves don't
look as though there is a very specific and sensitive cutoff value which could be used as a
prognostic indicator, which is somewhat one of the main goals of the paper.
The definition of ALF in the Introduction is poor - page 3 last sentence; the same definition as
per the later quoted APASL criteria or other commonly used definitions should be used "Bernal
et Wendon NEJM Dec 2013".
Do the authors think that the SOD levels are predominantly linked to organ failure and given
the difference ACLF vs ALF. Were the decompensated ACLF patients sicker in terms of MOF
which would also explain the high mortality? Are SOFA scores or other organ failure scores
available?
In other words is SOD just a marker of organ failure and associated ROS activation, rather than
HEV specific - this could be briefly appraised  in the Discussion and as a possible confounder.
Please review this paper.
user
Title: Serum Superoxide Dismutase Level Is a Potential Biomarker of Disease Prognosis in
Patients with HEV-induced Liver Failure
Version: 2 Date: 06 Dec 2021
Reviewer's report:
Many of my previously posed questions have been dealt with satisfactorily.
I would disagree with the comment that tissue cannot be used for diagnosis due to the risks
associated with biopsy and esp looking at the severity of disease esp in the ALF cohort (severity
of coagulopathy). TJ biopsy can be safely performed in ALF and coagulopathic patients; the
main problem is around sampling errors/diagnostic yield in case an area of necrosis is biopsied,
this may not be relevant in relation to SOD levels though.
Are there any animal experiments regarding tissue SOD levels in ALF? If so this should be
referenced.
In the  Methods and Result sections "HEV on the ground of ALD, CHB" should be changed  to
"on the background of ALD, CHB" and throughout the manuscript.
AUROC curves and levels should be provided for SOD, the area under the ROC curves don't
look as though there is a very specific and sensitive cutoff value which could be used as a
prognostic indicator, which is somewhat one of the main goals of the paper.
The definition of ALF in the Introduction is poor - page 3 last sentence; the same definition as
per the later quoted APASL criteria or other commonly used definitions should be used "Bernal
et Wendon NEJM Dec 2013".
Do the authors think that the SOD levels are predominantly linked to organ failure and given
the difference ACLF vs ALF. Were the decompensated ACLF patients sicker in terms of MOF
which would also explain the high mortality? Are SOFA scores or other organ failure scores
available?
In other words is SOD just a marker of organ failure and associated ROS activation, rather than
HEV specific - this could be briefly appraised  in the Discussion and as a possible confounder.
assistant