Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 1 Date: 06 May 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
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 technical rigor to allow
confidence in the results?
No - there are minor issues
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 - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The study demonstrated that in patients with acute-on-chronic
liver failure (ACLF), plasma adsorption (PA) and low-volume plasma exchange (PE) did not
significantly alter intracranial pressure (ICP). However, low-volume PE—but not PA—was
associated with significant increases in mean arterial pressure (MAP) and cerebral perfusion
pressure (CPP). These findings indicate that while both therapies appear safe in terms of ICP,
low-volume PE may confer additional circulatory benefits.
The study concept is interesting despite the negative results. A likely explanation is that the
included patients had ICP values within the normal range at baseline, limiting the potential for
measurable improvement. While the initial hypothesis may have been that artificial liver support
systems (ALSS) could improve hepatic encephalopathy (HE) partly through reducing ICP, the
authors were unable to demonstrate this effect. However, as shown in the Supplementary Table,
baseline ICP values were within normal limits, making further reduction less likely.
REQUESTED REVISIONS:
- It would be important to clarify whether any patients had elevated ICP (>20 mmHg), the typical
threshold for cerebral edema.
- Although the subgroup is small, an analysis of parameters specifically in patients with HE
would strengthen the study. How did pressures behave in this subgroup, and how did they change
following treatment?
- Additional details about ACLF precipitating factors would be valuable. From Table 1, it
appears that around half of the cases may have been precipitated by bacterial infections.
-The authors should also clarify what is meant by ""concomitant non-chronic liver disease""—
for example, does this refer to an acute hepatitis episode superimposed on chronic liver disease?"
Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 1 Date: 06 May 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
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 technical rigor to allow
confidence in the results?
No - there are minor issues
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 - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The study demonstrated that in patients with acute-on-chronic
liver failure (ACLF), plasma adsorption (PA) and low-volume plasma exchange (PE) did not
significantly alter intracranial pressure (ICP). However, low-volume PE—but not PA—was
associated with significant increases in mean arterial pressure (MAP) and cerebral perfusion
pressure (CPP). These findings indicate that while both therapies appear safe in terms of ICP,
low-volume PE may confer additional circulatory benefits.
The study concept is interesting despite the negative results. A likely explanation is that the
included patients had ICP values within the normal range at baseline, limiting the potential for
measurable improvement. While the initial hypothesis may have been that artificial liver support
systems (ALSS) could improve hepatic encephalopathy (HE) partly through reducing ICP, the
authors were unable to demonstrate this effect. However, as shown in the Supplementary Table,
baseline ICP values were within normal limits, making further reduction less likely.
REQUESTED REVISIONS:
- It would be important to clarify whether any patients had elevated ICP (>20 mmHg), the typical
threshold for cerebral edema.
- Although the subgroup is small, an analysis of parameters specifically in patients with HE
would strengthen the study. How did pressures behave in this subgroup, and how did they change
following treatment?
- Additional details about ACLF precipitating factors would be valuable. From Table 1, it
appears that around half of the cases may have been precipitated by bacterial infections.
-The authors should also clarify what is meant by ""concomitant non-chronic liver disease""—
for example, does this refer to an acute hepatitis episode superimposed on chronic liver disease?"
Please review this paper.
user
Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 1 Date: 06 May 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
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 technical rigor to allow
confidence in the results?
No - there are minor issues
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 - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The study demonstrated that in patients with acute-on-chronic
liver failure (ACLF), plasma adsorption (PA) and low-volume plasma exchange (PE) did not
significantly alter intracranial pressure (ICP). However, low-volume PE—but not PA—was
associated with significant increases in mean arterial pressure (MAP) and cerebral perfusion
pressure (CPP). These findings indicate that while both therapies appear safe in terms of ICP,
low-volume PE may confer additional circulatory benefits.
The study concept is interesting despite the negative results. A likely explanation is that the
included patients had ICP values within the normal range at baseline, limiting the potential for
measurable improvement. While the initial hypothesis may have been that artificial liver support
systems (ALSS) could improve hepatic encephalopathy (HE) partly through reducing ICP, the
authors were unable to demonstrate this effect. However, as shown in the Supplementary Table,
baseline ICP values were within normal limits, making further reduction less likely.
REQUESTED REVISIONS:
- It would be important to clarify whether any patients had elevated ICP (>20 mmHg), the typical
threshold for cerebral edema.
- Although the subgroup is small, an analysis of parameters specifically in patients with HE
would strengthen the study. How did pressures behave in this subgroup, and how did they change
following treatment?
- Additional details about ACLF precipitating factors would be valuable. From Table 1, it
appears that around half of the cases may have been precipitated by bacterial infections.
-The authors should also clarify what is meant by ""concomitant non-chronic liver disease""—
for example, does this refer to an acute hepatitis episode superimposed on chronic liver disease?"
assistant