Reviewer's report
Title:Non-Invasive Index of Liver Fibrosis Generated by Alcohol, Thioacetamide
and Schistosomal Infection in Mice
Version: 2Date:10 November 2009
Reviewer: giada Sebastiani
Reviewer's report:
Major concerns
- The authors should make a proper analysis of the performance of the
non-invasive model that they have generated, and this analysis should be shown
both in the abstract ad in the results. For all non-invasive markers proposed in
the literature the performance is expressed as accuracy, AUROC (with 95%
confidence interval), sensitivity, specificity, positive and negative predictive value,
likelihood ratios, as compared to histology considered as the gold standard.
These must be reported in Tables, and they must divided in training set of mice
and validation set of mice. These statistical indicators give an immediate idea of
the performance of the model proposed, then its possible application in clinical
practice. It is also mandatory that the authors clearly report the number
(percentage) of liver fibrosis stages by METAVIR at the various time points as
the performance of non-invasive fibrosis markers largely depend on the
prevalence of liver fibrosis stages. Moreover, one of the most important end-point
of non-invasive fibrosis assessment is cirrhosis, but authors did not clearly
assess performance of model in cirrhosis.
- In the discussion the authors propose an application of the new model on
human samples but it is really not clear what could be which kind of application
they are speaking of. The model has been developed in mice treated with TAA
(and this is not an etiology of liver disease in humans; may they intend chronic
drug damage?), with alcohol (could this be the application in humans?) and in
schistosomiasis. The authors should clearly explain what they intend as
application in humans, especially in clinical practice. The statement that their new
model correlates well with the corresponding liver histological stages is not
supported by the data reported and indeed is not very relevant in clinical practice
as the two most important stages of liver fibrosis that significantly change the
management of patients are significant fibrosis (> or = F2 by METAVIR) and
cirrhosis (F4 by METAVIR) (see recent reviews regarding this topic).
Minor concerns
- In the title, I would change "generated" with "induced".
- Introduction: Change "They also usually have 2 cut offs with and indeterminate
zone where the accuracy is less" with "Apart from Fibrotest, they also usually
have 2 cut offs with and indeterminate zone where the accuracy is less".
Some of the references are incomplete or outdated. Change the sentence: "They
can also be combined" with "They can also be combined in decisional
algorithms" and add the following references: Castera et al, Gastroenterology
2005; Sebastiani et al, Hepatology 2009. Replace reference 11 with Castera et
al, Gastroenterology 2005.
- Methods: METAVIR system is generally described as F0 to F4, not S0 to S4,
please correct. Also, it is not clear if the pathologist was single. In the logarithmic
formula, there is a mistake in the legenda: "gGGT= (delete "serum Where: Bil").
- Discussion: The sentence " Histologically, the highest fibrotic stage was
observed in mice with fibrosis" needs to be changed as it does not make sense.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Non-Invasive Index of Liver Fibrosis Generated by Alcohol, Thioacetamide
and Schistosomal Infection in Mice
Version: 2Date:10 November 2009
Reviewer: giada Sebastiani
Reviewer's report:
Major concerns
- The authors should make a proper analysis of the performance of the
non-invasive model that they have generated, and this analysis should be shown
both in the abstract ad in the results. For all non-invasive markers proposed in
the literature the performance is expressed as accuracy, AUROC (with 95%
confidence interval), sensitivity, specificity, positive and negative predictive value,
likelihood ratios, as compared to histology considered as the gold standard.
These must be reported in Tables, and they must divided in training set of mice
and validation set of mice. These statistical indicators give an immediate idea of
the performance of the model proposed, then its possible application in clinical
practice. It is also mandatory that the authors clearly report the number
(percentage) of liver fibrosis stages by METAVIR at the various time points as
the performance of non-invasive fibrosis markers largely depend on the
prevalence of liver fibrosis stages. Moreover, one of the most important end-point
of non-invasive fibrosis assessment is cirrhosis, but authors did not clearly
assess performance of model in cirrhosis.
- In the discussion the authors propose an application of the new model on
human samples but it is really not clear what could be which kind of application
they are speaking of. The model has been developed in mice treated with TAA
(and this is not an etiology of liver disease in humans; may they intend chronic
drug damage?), with alcohol (could this be the application in humans?) and in
schistosomiasis. The authors should clearly explain what they intend as
application in humans, especially in clinical practice. The statement that their new
model correlates well with the corresponding liver histological stages is not
supported by the data reported and indeed is not very relevant in clinical practice
as the two most important stages of liver fibrosis that significantly change the
management of patients are significant fibrosis (> or = F2 by METAVIR) and
cirrhosis (F4 by METAVIR) (see recent reviews regarding this topic).
Minor concerns
- In the title, I would change "generated" with "induced".
- Introduction: Change "They also usually have 2 cut offs with and indeterminate
zone where the accuracy is less" with "Apart from Fibrotest, they also usually
have 2 cut offs with and indeterminate zone where the accuracy is less".
Some of the references are incomplete or outdated. Change the sentence: "They
can also be combined" with "They can also be combined in decisional
algorithms" and add the following references: Castera et al, Gastroenterology
2005; Sebastiani et al, Hepatology 2009. Replace reference 11 with Castera et
al, Gastroenterology 2005.
- Methods: METAVIR system is generally described as F0 to F4, not S0 to S4,
please correct. Also, it is not clear if the pathologist was single. In the logarithmic
formula, there is a mistake in the legenda: "gGGT= (delete "serum Where: Bil").
- Discussion: The sentence " Histologically, the highest fibrotic stage was
observed in mice with fibrosis" needs to be changed as it does not make sense.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Non-Invasive Index of Liver Fibrosis Generated by Alcohol, Thioacetamide
and Schistosomal Infection in Mice
Version: 2Date:10 November 2009
Reviewer: giada Sebastiani
Reviewer's report:
Major concerns
- The authors should make a proper analysis of the performance of the
non-invasive model that they have generated, and this analysis should be shown
both in the abstract ad in the results. For all non-invasive markers proposed in
the literature the performance is expressed as accuracy, AUROC (with 95%
confidence interval), sensitivity, specificity, positive and negative predictive value,
likelihood ratios, as compared to histology considered as the gold standard.
These must be reported in Tables, and they must divided in training set of mice
and validation set of mice. These statistical indicators give an immediate idea of
the performance of the model proposed, then its possible application in clinical
practice. It is also mandatory that the authors clearly report the number
(percentage) of liver fibrosis stages by METAVIR at the various time points as
the performance of non-invasive fibrosis markers largely depend on the
prevalence of liver fibrosis stages. Moreover, one of the most important end-point
of non-invasive fibrosis assessment is cirrhosis, but authors did not clearly
assess performance of model in cirrhosis.
- In the discussion the authors propose an application of the new model on
human samples but it is really not clear what could be which kind of application
they are speaking of. The model has been developed in mice treated with TAA
(and this is not an etiology of liver disease in humans; may they intend chronic
drug damage?), with alcohol (could this be the application in humans?) and in
schistosomiasis. The authors should clearly explain what they intend as
application in humans, especially in clinical practice. The statement that their new
model correlates well with the corresponding liver histological stages is not
supported by the data reported and indeed is not very relevant in clinical practice
as the two most important stages of liver fibrosis that significantly change the
management of patients are significant fibrosis (> or = F2 by METAVIR) and
cirrhosis (F4 by METAVIR) (see recent reviews regarding this topic).
Minor concerns
- In the title, I would change "generated" with "induced".
- Introduction: Change "They also usually have 2 cut offs with and indeterminate
zone where the accuracy is less" with "Apart from Fibrotest, they also usually
have 2 cut offs with and indeterminate zone where the accuracy is less".
Some of the references are incomplete or outdated. Change the sentence: "They
can also be combined" with "They can also be combined in decisional
algorithms" and add the following references: Castera et al, Gastroenterology
2005; Sebastiani et al, Hepatology 2009. Replace reference 11 with Castera et
al, Gastroenterology 2005.
- Methods: METAVIR system is generally described as F0 to F4, not S0 to S4,
please correct. Also, it is not clear if the pathologist was single. In the logarithmic
formula, there is a mistake in the legenda: "gGGT= (delete "serum Where: Bil").
- Discussion: The sentence " Histologically, the highest fibrotic stage was
observed in mice with fibrosis" needs to be changed as it does not make sense.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
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