Reviewer's report
Title:Non-Invasive Biomarkers for Hepatic Fibrosis
Version: 1Date:14 April 2011
Reviewer: Laurent Castera
Reviewer's report:
The title of the review is misleading as it deals not only with biomarkers but also
with imaging techniques. Therefore, I would suggest something like:
“Non-invasive markers for hepatic fibrosis”
General comments
Overall the manuscript is too lengthy and needs to be more focused. The
introduction chapters (Biology, type and causes of liver fibrosis) are too long and
need to be shortened. For instance, I’m not sure that the chapter on type and
cause of liver fibrosis is relevant to the topic.
The following are my comments:
1. Endpoints
Basically, it’s important to stress the limitations of liver biopsy which fostered the
development of non invasive methods and the clinically-relevant endpoints
(significant fibrosis and cirrhosis) that may vary according to liver disease
etiologies. Significant fibrosis may not be as relevant in NAFLD (where the
current therapeutic options are limited) as in Hepatitis C.
2. Imaging techniques
The chapter on transient elastography needs to be expanded as in clinical
practice the alternative to biomarkers is the measurement of liver stiffness.
Although it is not approved yet in the US (and the authors may not have personal
experience for this reason), this technique is now widely used worldwide. The
quoted references are inappropriate. Please quote the index studies in Hep C as
well as meta-analyses. Also how transient elastography compare to biomarkers
should be addressed as well as how combination of biomarkers with transient
elastography may increase diagnostic accuracy.
Finally the limitations of this technique should be discussed in more details
particularly in patients with NAFLD as evidenced by a large French series
published last year (Castera et al. Hepatology 2010).
Although MRE is an interesting technique, data are limited and it remains
restricted to research purposes thus far. Another more promising technique
(ARFI) should be mentioned although results are still preliminary.
3. Performance of biomarkers
The chapter on biomarker is too lengthy and needs to be shortened. The review
would be more appealing to readers if performances of biomarkers were
summarized in tables rather than detailed in the text. I would suggest
summarizing the performances according to endpoints and causes of liver
diseases, viral hepatitis, NAFLD, etc… I would also emphasize that the most
used and validated biomarkers are currently APRI (free) and Fibrotest (patented).
Minor comment
I’m not sure that figure1 add much to the topic.
A figure summarizing how the authors suggest to use non invasive methods in
clinical practice would be more useful to the reader.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:Non-Invasive Biomarkers for Hepatic Fibrosis
Version: 1Date:14 April 2011
Reviewer: Laurent Castera
Reviewer's report:
The title of the review is misleading as it deals not only with biomarkers but also
with imaging techniques. Therefore, I would suggest something like:
“Non-invasive markers for hepatic fibrosis”
General comments
Overall the manuscript is too lengthy and needs to be more focused. The
introduction chapters (Biology, type and causes of liver fibrosis) are too long and
need to be shortened. For instance, I’m not sure that the chapter on type and
cause of liver fibrosis is relevant to the topic.
The following are my comments:
1. Endpoints
Basically, it’s important to stress the limitations of liver biopsy which fostered the
development of non invasive methods and the clinically-relevant endpoints
(significant fibrosis and cirrhosis) that may vary according to liver disease
etiologies. Significant fibrosis may not be as relevant in NAFLD (where the
current therapeutic options are limited) as in Hepatitis C.
2. Imaging techniques
The chapter on transient elastography needs to be expanded as in clinical
practice the alternative to biomarkers is the measurement of liver stiffness.
Although it is not approved yet in the US (and the authors may not have personal
experience for this reason), this technique is now widely used worldwide. The
quoted references are inappropriate. Please quote the index studies in Hep C as
well as meta-analyses. Also how transient elastography compare to biomarkers
should be addressed as well as how combination of biomarkers with transient
elastography may increase diagnostic accuracy.
Finally the limitations of this technique should be discussed in more details
particularly in patients with NAFLD as evidenced by a large French series
published last year (Castera et al. Hepatology 2010).
Although MRE is an interesting technique, data are limited and it remains
restricted to research purposes thus far. Another more promising technique
(ARFI) should be mentioned although results are still preliminary.
3. Performance of biomarkers
The chapter on biomarker is too lengthy and needs to be shortened. The review
would be more appealing to readers if performances of biomarkers were
summarized in tables rather than detailed in the text. I would suggest
summarizing the performances according to endpoints and causes of liver
diseases, viral hepatitis, NAFLD, etc… I would also emphasize that the most
used and validated biomarkers are currently APRI (free) and Fibrotest (patented).
Minor comment
I’m not sure that figure1 add much to the topic.
A figure summarizing how the authors suggest to use non invasive methods in
clinical practice would be more useful to the reader.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Non-Invasive Biomarkers for Hepatic Fibrosis
Version: 1Date:14 April 2011
Reviewer: Laurent Castera
Reviewer's report:
The title of the review is misleading as it deals not only with biomarkers but also
with imaging techniques. Therefore, I would suggest something like:
“Non-invasive markers for hepatic fibrosis”
General comments
Overall the manuscript is too lengthy and needs to be more focused. The
introduction chapters (Biology, type and causes of liver fibrosis) are too long and
need to be shortened. For instance, I’m not sure that the chapter on type and
cause of liver fibrosis is relevant to the topic.
The following are my comments:
1. Endpoints
Basically, it’s important to stress the limitations of liver biopsy which fostered the
development of non invasive methods and the clinically-relevant endpoints
(significant fibrosis and cirrhosis) that may vary according to liver disease
etiologies. Significant fibrosis may not be as relevant in NAFLD (where the
current therapeutic options are limited) as in Hepatitis C.
2. Imaging techniques
The chapter on transient elastography needs to be expanded as in clinical
practice the alternative to biomarkers is the measurement of liver stiffness.
Although it is not approved yet in the US (and the authors may not have personal
experience for this reason), this technique is now widely used worldwide. The
quoted references are inappropriate. Please quote the index studies in Hep C as
well as meta-analyses. Also how transient elastography compare to biomarkers
should be addressed as well as how combination of biomarkers with transient
elastography may increase diagnostic accuracy.
Finally the limitations of this technique should be discussed in more details
particularly in patients with NAFLD as evidenced by a large French series
published last year (Castera et al. Hepatology 2010).
Although MRE is an interesting technique, data are limited and it remains
restricted to research purposes thus far. Another more promising technique
(ARFI) should be mentioned although results are still preliminary.
3. Performance of biomarkers
The chapter on biomarker is too lengthy and needs to be shortened. The review
would be more appealing to readers if performances of biomarkers were
summarized in tables rather than detailed in the text. I would suggest
summarizing the performances according to endpoints and causes of liver
diseases, viral hepatitis, NAFLD, etc… I would also emphasize that the most
used and validated biomarkers are currently APRI (free) and Fibrotest (patented).
Minor comment
I’m not sure that figure1 add much to the topic.
A figure summarizing how the authors suggest to use non invasive methods in
clinical practice would be more useful to the reader.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
assistant