Reviewer's report
Title:White cell count and platelet count associate with histological alcoholic
hepatitis in jaundiced harmful drinkers
Version: 2Date:24 October 2012
Reviewer: Philippe Mathurin
Reviewer's report:
This study evaluates the frequency of biopsy-proven alcoholic hepatitis in
patients admitted with a suspected diagnosis of severe alcoholic hepatitis based
on biological and clinical features. The objective of this study is relevant as some
investigators are still reluctant to consider liver biopsy as a prerequisite criterion
for the treatment of patients with aggressive forms of ALD requiring specific
interventions or for the setting of studies evaluating new therapies. As only 75 %
of patients with presumed diagnosis of alcoholic hepatitis disclose biopsy-proven
alcoholic hepatitis, this study supports the conclusions of the recent EASL
guidelines on Alcoholic liver disease for the use of liver biopsy in the setting of
alcoholic hepatitis. I suggest some modifications in order to improve the quality of
this work.
Major comments
1. The authors need to include in the references and to discuss the recent
published EASL Clinical Practical Guidelines on Alcoholic Liver Disease [J
Hepatol 2012;57:399-420]
2. The authors need to provide all details on histological analysis on overall
patients: a/What are the histological features for patients without biopsy-proven
alcoholic hepatitis? b/ What are the histological features s of patients with
biopsy-proven alcoholic hepatitis? Do the pathologist use a histological grading
of severity of alcoholic hepatitis in terms of hepatocyte ballooning and of
inflammatory infiltrate?
3. Although the presence of Mallory-Denk’s bodie is not considered as
necessary, it would be interesting to specify the percentage of patients disclosing
this histological feature.
4. The authors state on page 7: “There was no difference in the mean age,
Child’s score, DF, prothrombin time or serum concentrations of creatinine,
bilirubin, albumin, alkaline phosphatase and alanine transaminase between the
group with histological alcoholic hepatitis and those without.” This sentence is
inaccurate when considering the limited sample size. As an example, the lack of
significance for bilirubin (431 vs 307 µmol/l) is probably attributed to a type II
error consisting in the failure to reject a false null hypothesis.
5. In table 1, p values need to be provided for all comparisons including the non
significant.
6. The authors need to clearly discuss their results in terms of the use of liver
biopsy in the setting of trials. How can we accept the possibility of 25% of false
inclusions if we are testing therapy with an expect impact of 20-30% in terms of
short-term survival? I suggest emphasizing this point in the conclusion of the
abstract, as well. This is a crucial point for the development of future therapies
aiming to improve the outcome of patients suffering from this life-threatening
disease.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I do not have conflit of interests related to this manuscript.
Reviewer's report
Title:White cell count and platelet count associate with histological alcoholic
hepatitis in jaundiced harmful drinkers
Version: 2Date:24 October 2012
Reviewer: Philippe Mathurin
Reviewer's report:
This study evaluates the frequency of biopsy-proven alcoholic hepatitis in
patients admitted with a suspected diagnosis of severe alcoholic hepatitis based
on biological and clinical features. The objective of this study is relevant as some
investigators are still reluctant to consider liver biopsy as a prerequisite criterion
for the treatment of patients with aggressive forms of ALD requiring specific
interventions or for the setting of studies evaluating new therapies. As only 75 %
of patients with presumed diagnosis of alcoholic hepatitis disclose biopsy-proven
alcoholic hepatitis, this study supports the conclusions of the recent EASL
guidelines on Alcoholic liver disease for the use of liver biopsy in the setting of
alcoholic hepatitis. I suggest some modifications in order to improve the quality of
this work.
Major comments
1. The authors need to include in the references and to discuss the recent
published EASL Clinical Practical Guidelines on Alcoholic Liver Disease [J
Hepatol 2012;57:399-420]
2. The authors need to provide all details on histological analysis on overall
patients: a/What are the histological features for patients without biopsy-proven
alcoholic hepatitis? b/ What are the histological features s of patients with
biopsy-proven alcoholic hepatitis? Do the pathologist use a histological grading
of severity of alcoholic hepatitis in terms of hepatocyte ballooning and of
inflammatory infiltrate?
3. Although the presence of Mallory-Denk’s bodie is not considered as
necessary, it would be interesting to specify the percentage of patients disclosing
this histological feature.
4. The authors state on page 7: “There was no difference in the mean age,
Child’s score, DF, prothrombin time or serum concentrations of creatinine,
bilirubin, albumin, alkaline phosphatase and alanine transaminase between the
group with histological alcoholic hepatitis and those without.” This sentence is
inaccurate when considering the limited sample size. As an example, the lack of
significance for bilirubin (431 vs 307 µmol/l) is probably attributed to a type II
error consisting in the failure to reject a false null hypothesis.
5. In table 1, p values need to be provided for all comparisons including the non
significant.
6. The authors need to clearly discuss their results in terms of the use of liver
biopsy in the setting of trials. How can we accept the possibility of 25% of false
inclusions if we are testing therapy with an expect impact of 20-30% in terms of
short-term survival? I suggest emphasizing this point in the conclusion of the
abstract, as well. This is a crucial point for the development of future therapies
aiming to improve the outcome of patients suffering from this life-threatening
disease.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I do not have conflit of interests related to this manuscript.
Please review this paper.
user
Reviewer's report
Title:White cell count and platelet count associate with histological alcoholic
hepatitis in jaundiced harmful drinkers
Version: 2Date:24 October 2012
Reviewer: Philippe Mathurin
Reviewer's report:
This study evaluates the frequency of biopsy-proven alcoholic hepatitis in
patients admitted with a suspected diagnosis of severe alcoholic hepatitis based
on biological and clinical features. The objective of this study is relevant as some
investigators are still reluctant to consider liver biopsy as a prerequisite criterion
for the treatment of patients with aggressive forms of ALD requiring specific
interventions or for the setting of studies evaluating new therapies. As only 75 %
of patients with presumed diagnosis of alcoholic hepatitis disclose biopsy-proven
alcoholic hepatitis, this study supports the conclusions of the recent EASL
guidelines on Alcoholic liver disease for the use of liver biopsy in the setting of
alcoholic hepatitis. I suggest some modifications in order to improve the quality of
this work.
Major comments
1. The authors need to include in the references and to discuss the recent
published EASL Clinical Practical Guidelines on Alcoholic Liver Disease [J
Hepatol 2012;57:399-420]
2. The authors need to provide all details on histological analysis on overall
patients: a/What are the histological features for patients without biopsy-proven
alcoholic hepatitis? b/ What are the histological features s of patients with
biopsy-proven alcoholic hepatitis? Do the pathologist use a histological grading
of severity of alcoholic hepatitis in terms of hepatocyte ballooning and of
inflammatory infiltrate?
3. Although the presence of Mallory-Denk’s bodie is not considered as
necessary, it would be interesting to specify the percentage of patients disclosing
this histological feature.
4. The authors state on page 7: “There was no difference in the mean age,
Child’s score, DF, prothrombin time or serum concentrations of creatinine,
bilirubin, albumin, alkaline phosphatase and alanine transaminase between the
group with histological alcoholic hepatitis and those without.” This sentence is
inaccurate when considering the limited sample size. As an example, the lack of
significance for bilirubin (431 vs 307 µmol/l) is probably attributed to a type II
error consisting in the failure to reject a false null hypothesis.
5. In table 1, p values need to be provided for all comparisons including the non
significant.
6. The authors need to clearly discuss their results in terms of the use of liver
biopsy in the setting of trials. How can we accept the possibility of 25% of false
inclusions if we are testing therapy with an expect impact of 20-30% in terms of
short-term survival? I suggest emphasizing this point in the conclusion of the
abstract, as well. This is a crucial point for the development of future therapies
aiming to improve the outcome of patients suffering from this life-threatening
disease.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I do not have conflit of interests related to this manuscript.
assistant