Reviewer's report 
 Serum hyaluronate as a Non-invasive Marker of Hepatic Fibrosis and Inflammation in Title: 
HBeAg-negative Chronic Hepatitis B 
 4  19 July 2005 Version: Date: 
 Edoardo Giovanni Giannini Reviewer: 
Reviewer's report: 
General 
The manuscript was greatly improved. I appreciated the thoughtful review of the paper made by the 
Authors. However, there are still some points that need to be addressed. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
1. The Authors state that they aimed at evaluating the usefulness of HA for discrimination of "levels 
of fibrosis". On the basis of the typology of patients studied and of the obtained results, I would suggest that the aim should be "to evaluate the presence of extensive fibrosis in patients with 
chronic hepatitis B". 
2. Methods. The Authors should report in the text that their pathologist was unable to differentiate 
fibrosis stage 5 and 6. 
3. I would be glad to see a scattergram of the HA serum levels plotted against fibrosis scores. 
4. Discussion, page 9, second paragraph (HA cut-offs): The Authors should add that the cut-off 
value for a given variable depends upon the sample in which it has been identified. In order to be 
reproducible, a cut-off value should be obtained in a sample representative of the population with 
the disease. 5. Discussion, page 9, third paragraph (HA predictive values): Fifty-four out of 65 patients had 
extensive fibrosis, and 54 out of 65 had "extensive" inflammation. What was the relationship 
between these two histological features in this cohort? 
6. Discussion, page 10, last paragraph: On the basis of their results, the Authors can conclude that HA was correlated with stage and predictive for the presence of extensive fibrosis but not "predictive 
for the level of fibrosis". 
------------------------------------------------------------------------------- Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
1. Abstract, Conclusions, first line: I would suggest "Serum hyaluronate was the best predictor of the 
presence of extensive fibrosis..." rather than "...of the presence of liver fibrosis...". 
2. Background, first line: HBV should be spelled out the first tme it is cited in the text. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Serum hyaluronate as a Non-invasive Marker of Hepatic Fibrosis and Inflammation in Title: 
HBeAg-negative Chronic Hepatitis B 
 4  19 July 2005 Version: Date: 
 Edoardo Giovanni Giannini Reviewer: 
Reviewer's report: 
General 
The manuscript was greatly improved. I appreciated the thoughtful review of the paper made by the 
Authors. However, there are still some points that need to be addressed. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
1. The Authors state that they aimed at evaluating the usefulness of HA for discrimination of "levels 
of fibrosis". On the basis of the typology of patients studied and of the obtained results, I would suggest that the aim should be "to evaluate the presence of extensive fibrosis in patients with 
chronic hepatitis B". 
2. Methods. The Authors should report in the text that their pathologist was unable to differentiate 
fibrosis stage 5 and 6. 
3. I would be glad to see a scattergram of the HA serum levels plotted against fibrosis scores. 
4. Discussion, page 9, second paragraph (HA cut-offs): The Authors should add that the cut-off 
value for a given variable depends upon the sample in which it has been identified. In order to be 
reproducible, a cut-off value should be obtained in a sample representative of the population with 
the disease. 5. Discussion, page 9, third paragraph (HA predictive values): Fifty-four out of 65 patients had 
extensive fibrosis, and 54 out of 65 had "extensive" inflammation. What was the relationship 
between these two histological features in this cohort? 
6. Discussion, page 10, last paragraph: On the basis of their results, the Authors can conclude that HA was correlated with stage and predictive for the presence of extensive fibrosis but not "predictive 
for the level of fibrosis". 
------------------------------------------------------------------------------- Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
1. Abstract, Conclusions, first line: I would suggest "Serum hyaluronate was the best predictor of the 
presence of extensive fibrosis..." rather than "...of the presence of liver fibrosis...". 
2. Background, first line: HBV should be spelled out the first tme it is cited in the text. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Serum hyaluronate as a Non-invasive Marker of Hepatic Fibrosis and Inflammation in Title: 
HBeAg-negative Chronic Hepatitis B 
 4  19 July 2005 Version: Date: 
 Edoardo Giovanni Giannini Reviewer: 
Reviewer's report: 
General 
The manuscript was greatly improved. I appreciated the thoughtful review of the paper made by the 
Authors. However, there are still some points that need to be addressed. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
1. The Authors state that they aimed at evaluating the usefulness of HA for discrimination of "levels 
of fibrosis". On the basis of the typology of patients studied and of the obtained results, I would suggest that the aim should be "to evaluate the presence of extensive fibrosis in patients with 
chronic hepatitis B". 
2. Methods. The Authors should report in the text that their pathologist was unable to differentiate 
fibrosis stage 5 and 6. 
3. I would be glad to see a scattergram of the HA serum levels plotted against fibrosis scores. 
4. Discussion, page 9, second paragraph (HA cut-offs): The Authors should add that the cut-off 
value for a given variable depends upon the sample in which it has been identified. In order to be 
reproducible, a cut-off value should be obtained in a sample representative of the population with 
the disease. 5. Discussion, page 9, third paragraph (HA predictive values): Fifty-four out of 65 patients had 
extensive fibrosis, and 54 out of 65 had "extensive" inflammation. What was the relationship 
between these two histological features in this cohort? 
6. Discussion, page 10, last paragraph: On the basis of their results, the Authors can conclude that HA was correlated with stage and predictive for the presence of extensive fibrosis but not "predictive 
for the level of fibrosis". 
------------------------------------------------------------------------------- Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
1. Abstract, Conclusions, first line: I would suggest "Serum hyaluronate was the best predictor of the 
presence of extensive fibrosis..." rather than "...of the presence of liver fibrosis...". 
2. Background, first line: HBV should be spelled out the first tme it is cited in the text. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant