Reviewer's report
Title:Plasma Pentraxin3 is a Novel Marker for Nonalcoholic Steatohepatitis
(NASH)
Version: 1Date:18 July 2008
Reviewer: Joel E Lavine
Reviewer's report:
This manuscript by Yoneda et al addresses the utility of a plasma pentraxin3 in
the diagnosis, staging and grading of nonalcoholic fatty liver disease.
Development and validation of serum markers or imaging tools to assist in
diagnosis is much needed to minimize the need for liver biopsy, which is the only
method currently used to stage and grade fatty liver. NAFLD is a common and
increasingly prevalent problem in many parts of the world, so rapid, accurate and
non-invasive surrogates are important.
Major compulsory revisions:
1) Some terminology is inaccurate. I would not call NAFLD with stage 0-2 fibrosis
"non-advanced" and stages 3-4 "advanced". I think it should be called Stages 0-2
vs. Stages 3-4. The terms "simple steatosis" vs. NASH are not clear, since some
with "simple steatosis" have inflammation (table 1). I think the authors can call
this "not NASH" and "NASH", all within the category of NAFLD.
2) This work does not address the relation between PTX3 and pathogenesis or
progression (in a longitudinal sense), so the Aims in the abstract should be
amended.
3) A power calculation for determining sample size would have been appropriate.
4) Relations between CRP, sedimentation rate and PTX3 would be useful, and
should be provided. Hopefully this would let readers know whether PTX3
provides additional benefit beyond these other inflammatory indices.
5) Other laboratory data such as ALT, AST, hyaluronic acid, type 4 collagen,
platelet and albumin demonstrated significance between classes of NAFLD
examined. How does inclusion of these variables in multivariate regression
models change the predictive value of PTX3?
6) Figure 3 should be eliminated since it is not significant.
7) Discusssion should include if and whether PTX3 can or could replace liver
biopsy, and if so, how? If not, see if combination of other significant tests can.
8) It should be stated if pathologist blinded to laboratory results
9) Samples should have been tested prospectively using ROC cut-offs selected
to determine utility of this test.
10) In figures, how do "outliers" extend beyond the range? What is the definition
of an outlier?
Minor essentional revisions include:
1) Background states liver biopsy has "relatively high rate of complications".
Relatively high compared to what? Does this mean that hepatologists should not
perform this test? I believe it would be sufficient to state that avoidance of liver
biopsy would be desirable.
2) Methods does not state that patients with drugs causing fatty liver disease
were excluded. Were they?
3)Last sentence of conclusion should be removed, as this study does not
address the prognostic value of PTX3 levels on outcome.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Plasma Pentraxin3 is a Novel Marker for Nonalcoholic Steatohepatitis
(NASH)
Version: 1Date:18 July 2008
Reviewer: Joel E Lavine
Reviewer's report:
This manuscript by Yoneda et al addresses the utility of a plasma pentraxin3 in
the diagnosis, staging and grading of nonalcoholic fatty liver disease.
Development and validation of serum markers or imaging tools to assist in
diagnosis is much needed to minimize the need for liver biopsy, which is the only
method currently used to stage and grade fatty liver. NAFLD is a common and
increasingly prevalent problem in many parts of the world, so rapid, accurate and
non-invasive surrogates are important.
Major compulsory revisions:
1) Some terminology is inaccurate. I would not call NAFLD with stage 0-2 fibrosis
"non-advanced" and stages 3-4 "advanced". I think it should be called Stages 0-2
vs. Stages 3-4. The terms "simple steatosis" vs. NASH are not clear, since some
with "simple steatosis" have inflammation (table 1). I think the authors can call
this "not NASH" and "NASH", all within the category of NAFLD.
2) This work does not address the relation between PTX3 and pathogenesis or
progression (in a longitudinal sense), so the Aims in the abstract should be
amended.
3) A power calculation for determining sample size would have been appropriate.
4) Relations between CRP, sedimentation rate and PTX3 would be useful, and
should be provided. Hopefully this would let readers know whether PTX3
provides additional benefit beyond these other inflammatory indices.
5) Other laboratory data such as ALT, AST, hyaluronic acid, type 4 collagen,
platelet and albumin demonstrated significance between classes of NAFLD
examined. How does inclusion of these variables in multivariate regression
models change the predictive value of PTX3?
6) Figure 3 should be eliminated since it is not significant.
7) Discusssion should include if and whether PTX3 can or could replace liver
biopsy, and if so, how? If not, see if combination of other significant tests can.
8) It should be stated if pathologist blinded to laboratory results
9) Samples should have been tested prospectively using ROC cut-offs selected
to determine utility of this test.
10) In figures, how do "outliers" extend beyond the range? What is the definition
of an outlier?
Minor essentional revisions include:
1) Background states liver biopsy has "relatively high rate of complications".
Relatively high compared to what? Does this mean that hepatologists should not
perform this test? I believe it would be sufficient to state that avoidance of liver
biopsy would be desirable.
2) Methods does not state that patients with drugs causing fatty liver disease
were excluded. Were they?
3)Last sentence of conclusion should be removed, as this study does not
address the prognostic value of PTX3 levels on outcome.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Plasma Pentraxin3 is a Novel Marker for Nonalcoholic Steatohepatitis
(NASH)
Version: 1Date:18 July 2008
Reviewer: Joel E Lavine
Reviewer's report:
This manuscript by Yoneda et al addresses the utility of a plasma pentraxin3 in
the diagnosis, staging and grading of nonalcoholic fatty liver disease.
Development and validation of serum markers or imaging tools to assist in
diagnosis is much needed to minimize the need for liver biopsy, which is the only
method currently used to stage and grade fatty liver. NAFLD is a common and
increasingly prevalent problem in many parts of the world, so rapid, accurate and
non-invasive surrogates are important.
Major compulsory revisions:
1) Some terminology is inaccurate. I would not call NAFLD with stage 0-2 fibrosis
"non-advanced" and stages 3-4 "advanced". I think it should be called Stages 0-2
vs. Stages 3-4. The terms "simple steatosis" vs. NASH are not clear, since some
with "simple steatosis" have inflammation (table 1). I think the authors can call
this "not NASH" and "NASH", all within the category of NAFLD.
2) This work does not address the relation between PTX3 and pathogenesis or
progression (in a longitudinal sense), so the Aims in the abstract should be
amended.
3) A power calculation for determining sample size would have been appropriate.
4) Relations between CRP, sedimentation rate and PTX3 would be useful, and
should be provided. Hopefully this would let readers know whether PTX3
provides additional benefit beyond these other inflammatory indices.
5) Other laboratory data such as ALT, AST, hyaluronic acid, type 4 collagen,
platelet and albumin demonstrated significance between classes of NAFLD
examined. How does inclusion of these variables in multivariate regression
models change the predictive value of PTX3?
6) Figure 3 should be eliminated since it is not significant.
7) Discusssion should include if and whether PTX3 can or could replace liver
biopsy, and if so, how? If not, see if combination of other significant tests can.
8) It should be stated if pathologist blinded to laboratory results
9) Samples should have been tested prospectively using ROC cut-offs selected
to determine utility of this test.
10) In figures, how do "outliers" extend beyond the range? What is the definition
of an outlier?
Minor essentional revisions include:
1) Background states liver biopsy has "relatively high rate of complications".
Relatively high compared to what? Does this mean that hepatologists should not
perform this test? I believe it would be sufficient to state that avoidance of liver
biopsy would be desirable.
2) Methods does not state that patients with drugs causing fatty liver disease
were excluded. Were they?
3)Last sentence of conclusion should be removed, as this study does not
address the prognostic value of PTX3 levels on outcome.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
assistant