Reviewer ’s report  
 
Title: Pruritus in patients with chronic liver disease and serum au totaxin levels in patients with 
primary biliary cholangitis  
 
Version: 0 Date: 24 Aug 2019  
 
Reviewer: Hirokazu Takahashi  
 
Reviewer's report:  
 
Manuscript Number: BMGE -D-19-00449  
 
Full Title: Pruritus in patients with chroni c liver disease and ser um autotaxin levels in patients 
with primary biliary cholangitis  
 
The authors investigated prevalence and severity of pruritus in the 2477 patients with chronic 
liver disease. Using numerical rating scale (NRS), the authors clearly d emonstrated the data in 
individual chronic liver disease. Furthermore, the authors focused on pruritus in PBC and 
analyzed association between autotaxin and pruritus.  
 
 
Major  
 
1. Whereas correlation between autotaxin and NRS in PBC was not significant, the  authors 
should show this missing data. Otherwise, autotaxin -related analysis seems to be abrupt 
and out of main purpose of this study. Moreover, authors should explain their hypothesis 
and study design why not other fibrosis markers, but autotaxin was tes ted in the 
correlation with NRS. No actual data was presented in this manuscript to support 
description below. Page 8 ："The relationship between autotaxin levels and pruritus was 
analyzed; however, the levels were not correlated with severity of pruritus. I n patients 
with PBC, no factor was significantly correlated with severe pruritus." Page 10 ："In 
contrast, this study on Japanese PBC patients showed no association between pruritus and 
liver fibrosis markers, including serum autotaxin" Page 11: "however, it  is not a 
predictive marker for severe pruritus in patients with PBC." This reviewer thinks more 
detail information and analysis of PBC cohort with autotaxin measurement should be 
demonstrated in this manuscript.  
 
 
Minor  
 
1. This study cohort includes many HCV antibody positive patients; however, it is unknow 
if they received anti -HCV therapy and achieved sustained viral response.   
 
2. Measurement of autotaxin in PBC patients. According to the method (page 6), the authors 
measure autotaxin in 114 patients, s uggesting that 5 patients were removed from this 
analysis. Authors should explain about this issue. The number of the patients with 
NRS≥5 or <5 should be described again in the 114 patients.  
 
3. Figure 2 and result (page 7) ："NRS was high in patients with ch ronic liver disease, 
especially in those with PBC, as is generally expected." In order to compare NRS among 
the chronic liver diseases, median of NRS of individual liver disease is important 
information and should be described.   
 
4. Please double check the number of HBV patients; 718 in page 5 and 719 in table 1.  
 
5. Which factors were tested in the multivariate analysis? Significant ones in univariate 
analysis?  
 
6. Was FibroScan data reliable in all cases?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary 
from an  organisation that may  in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either n ow or in the 
future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating t o the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing int erests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Acc ess Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Pruritus in patients with chronic liver disease and serum au totaxin levels in patients with 
primary biliary cholangitis  
 
Version: 0 Date: 24 Aug 2019  
 
Reviewer: Hirokazu Takahashi  
 
Reviewer's report:  
 
Manuscript Number: BMGE -D-19-00449  
 
Full Title: Pruritus in patients with chroni c liver disease and ser um autotaxin levels in patients 
with primary biliary cholangitis  
 
The authors investigated prevalence and severity of pruritus in the 2477 patients with chronic 
liver disease. Using numerical rating scale (NRS), the authors clearly d emonstrated the data in 
individual chronic liver disease. Furthermore, the authors focused on pruritus in PBC and 
analyzed association between autotaxin and pruritus.  
 
 
Major  
 
1. Whereas correlation between autotaxin and NRS in PBC was not significant, the  authors 
should show this missing data. Otherwise, autotaxin -related analysis seems to be abrupt 
and out of main purpose of this study. Moreover, authors should explain their hypothesis 
and study design why not other fibrosis markers, but autotaxin was tes ted in the 
correlation with NRS. No actual data was presented in this manuscript to support 
description below. Page 8 ："The relationship between autotaxin levels and pruritus was 
analyzed; however, the levels were not correlated with severity of pruritus. I n patients 
with PBC, no factor was significantly correlated with severe pruritus." Page 10 ："In 
contrast, this study on Japanese PBC patients showed no association between pruritus and 
liver fibrosis markers, including serum autotaxin" Page 11: "however, it  is not a 
predictive marker for severe pruritus in patients with PBC." This reviewer thinks more 
detail information and analysis of PBC cohort with autotaxin measurement should be 
demonstrated in this manuscript.  
 
 
Minor  
 
1. This study cohort includes many HCV antibody positive patients; however, it is unknow 
if they received anti -HCV therapy and achieved sustained viral response.   
 
2. Measurement of autotaxin in PBC patients. According to the method (page 6), the authors 
measure autotaxin in 114 patients, s uggesting that 5 patients were removed from this 
analysis. Authors should explain about this issue. The number of the patients with 
NRS≥5 or <5 should be described again in the 114 patients.  
 
3. Figure 2 and result (page 7) ："NRS was high in patients with ch ronic liver disease, 
especially in those with PBC, as is generally expected." In order to compare NRS among 
the chronic liver diseases, median of NRS of individual liver disease is important 
information and should be described.   
 
4. Please double check the number of HBV patients; 718 in page 5 and 719 in table 1.  
 
5. Which factors were tested in the multivariate analysis? Significant ones in univariate 
analysis?  
 
6. Was FibroScan data reliable in all cases?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary 
from an  organisation that may  in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either n ow or in the 
future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating t o the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing int erests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Acc ess Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Pruritus in patients with chronic liver disease and serum au totaxin levels in patients with 
primary biliary cholangitis  
 
Version: 0 Date: 24 Aug 2019  
 
Reviewer: Hirokazu Takahashi  
 
Reviewer's report:  
 
Manuscript Number: BMGE -D-19-00449  
 
Full Title: Pruritus in patients with chroni c liver disease and ser um autotaxin levels in patients 
with primary biliary cholangitis  
 
The authors investigated prevalence and severity of pruritus in the 2477 patients with chronic 
liver disease. Using numerical rating scale (NRS), the authors clearly d emonstrated the data in 
individual chronic liver disease. Furthermore, the authors focused on pruritus in PBC and 
analyzed association between autotaxin and pruritus.  
 
 
Major  
 
1. Whereas correlation between autotaxin and NRS in PBC was not significant, the  authors 
should show this missing data. Otherwise, autotaxin -related analysis seems to be abrupt 
and out of main purpose of this study. Moreover, authors should explain their hypothesis 
and study design why not other fibrosis markers, but autotaxin was tes ted in the 
correlation with NRS. No actual data was presented in this manuscript to support 
description below. Page 8 ："The relationship between autotaxin levels and pruritus was 
analyzed; however, the levels were not correlated with severity of pruritus. I n patients 
with PBC, no factor was significantly correlated with severe pruritus." Page 10 ："In 
contrast, this study on Japanese PBC patients showed no association between pruritus and 
liver fibrosis markers, including serum autotaxin" Page 11: "however, it  is not a 
predictive marker for severe pruritus in patients with PBC." This reviewer thinks more 
detail information and analysis of PBC cohort with autotaxin measurement should be 
demonstrated in this manuscript.  
 
 
Minor  
 
1. This study cohort includes many HCV antibody positive patients; however, it is unknow 
if they received anti -HCV therapy and achieved sustained viral response.   
 
2. Measurement of autotaxin in PBC patients. According to the method (page 6), the authors 
measure autotaxin in 114 patients, s uggesting that 5 patients were removed from this 
analysis. Authors should explain about this issue. The number of the patients with 
NRS≥5 or <5 should be described again in the 114 patients.  
 
3. Figure 2 and result (page 7) ："NRS was high in patients with ch ronic liver disease, 
especially in those with PBC, as is generally expected." In order to compare NRS among 
the chronic liver diseases, median of NRS of individual liver disease is important 
information and should be described.   
 
4. Please double check the number of HBV patients; 718 in page 5 and 719 in table 1.  
 
5. Which factors were tested in the multivariate analysis? Significant ones in univariate 
analysis?  
 
6. Was FibroScan data reliable in all cases?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary 
from an  organisation that may  in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either n ow or in the 
future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content 
of the manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating t o the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing int erests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Acc ess Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant