Reviewer’s report
Title: A Case Series Evaluating the Impact of Hepatitis C Eradication using Direct Acting Antivirals on
Primary Biliary Cholangitis-Associated Autoimmunity.
Version: 1 Date: 24 Jan 2018
Reviewer: Alessandra Mangia
Reviewer's report:
This is an interesting case series focusing on a subgroup of patients with HCV infection and associated
primary biliary cholangitis. This association reported in less than 10% of patients with HCV chronic
infection (Floreani A et al 2003) may be considered an intriguing clinical model.
The Authors describe the ALT/AST levels before and during HCV treatment as well as the fluctuations
in the titres of anti-mitocondrial and anti 3E subunity-BPO.  In two of three patients described here
after an initial decline in autoantibodies titres a following increase during  antiviral treatment was
reported.
Of note,  all  the  patients  considered  in  the  manuscript  achieved  HCV viral  clearance  after  DAA
treatment and regardless of the adopted antiviral regimen. 
The  limitation  of  this  paper  is  the  small  number  of  patients  and  the  differences  in  the  primary
cholangitis treatment (UDCA was used in only one of the three patients). By contrast, the topic is
original and a complete profiling of antibody reactivity is available for every patient.
Main points
My question for the Authors is the following: how they explain the initial decline in antibodies titers?
Was it specific or there are other reports  looking at coexistence of  autoantibodies/autoimmune
diseases  in  HCV  patients?  For  example  in  subjects  positive  for  antithyroid  peroxidase  or  anti
thyroglobulin antibodies?
Can  we  hypothesize  that  with  a  longer  follow  up,  after  HCV  DAA-induced  eradication,  an
improvement of the underlying autoimmune disease can be expected?  Please include all comments for
the authors in this box rather than uploading your report as an attachment. Please only upload as
attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your
report which cannot be included in a text format.
Please overwrite this text when adding your comments to the authors.
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.
Unable to assess
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 manuscript or would you recommend an additional 
statistical review?
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
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 financially from the publication of this 
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially 
from the publication of this manuscript, either now 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 to 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 interests' below. If 
your reply is yes to any, please give details below.
I declare that I have not competing interests
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for 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 Access 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 included 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: A Case Series Evaluating the Impact of Hepatitis C Eradication using Direct Acting Antivirals on
Primary Biliary Cholangitis-Associated Autoimmunity.
Version: 1 Date: 24 Jan 2018
Reviewer: Alessandra Mangia
Reviewer's report:
This is an interesting case series focusing on a subgroup of patients with HCV infection and associated
primary biliary cholangitis. This association reported in less than 10% of patients with HCV chronic
infection (Floreani A et al 2003) may be considered an intriguing clinical model.
The Authors describe the ALT/AST levels before and during HCV treatment as well as the fluctuations
in the titres of anti-mitocondrial and anti 3E subunity-BPO.  In two of three patients described here
after an initial decline in autoantibodies titres a following increase during  antiviral treatment was
reported.
Of note,  all  the  patients  considered  in  the  manuscript  achieved  HCV viral  clearance  after  DAA
treatment and regardless of the adopted antiviral regimen. 
The  limitation  of  this  paper  is  the  small  number  of  patients  and  the  differences  in  the  primary
cholangitis treatment (UDCA was used in only one of the three patients). By contrast, the topic is
original and a complete profiling of antibody reactivity is available for every patient.
Main points
My question for the Authors is the following: how they explain the initial decline in antibodies titers?
Was it specific or there are other reports  looking at coexistence of  autoantibodies/autoimmune
diseases  in  HCV  patients?  For  example  in  subjects  positive  for  antithyroid  peroxidase  or  anti
thyroglobulin antibodies?
Can  we  hypothesize  that  with  a  longer  follow  up,  after  HCV  DAA-induced  eradication,  an
improvement of the underlying autoimmune disease can be expected?  Please include all comments for
the authors in this box rather than uploading your report as an attachment. Please only upload as
attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your
report which cannot be included in a text format.
Please overwrite this text when adding your comments to the authors.
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.
Unable to assess
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 manuscript or would you recommend an additional 
statistical review?
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
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 financially from the publication of this 
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially 
from the publication of this manuscript, either now 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 to 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 interests' below. If 
your reply is yes to any, please give details below.
I declare that I have not competing interests
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for 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 Access 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 included 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: A Case Series Evaluating the Impact of Hepatitis C Eradication using Direct Acting Antivirals on
Primary Biliary Cholangitis-Associated Autoimmunity.
Version: 1 Date: 24 Jan 2018
Reviewer: Alessandra Mangia
Reviewer's report:
This is an interesting case series focusing on a subgroup of patients with HCV infection and associated
primary biliary cholangitis. This association reported in less than 10% of patients with HCV chronic
infection (Floreani A et al 2003) may be considered an intriguing clinical model.
The Authors describe the ALT/AST levels before and during HCV treatment as well as the fluctuations
in the titres of anti-mitocondrial and anti 3E subunity-BPO.  In two of three patients described here
after an initial decline in autoantibodies titres a following increase during  antiviral treatment was
reported.
Of note,  all  the  patients  considered  in  the  manuscript  achieved  HCV viral  clearance  after  DAA
treatment and regardless of the adopted antiviral regimen. 
The  limitation  of  this  paper  is  the  small  number  of  patients  and  the  differences  in  the  primary
cholangitis treatment (UDCA was used in only one of the three patients). By contrast, the topic is
original and a complete profiling of antibody reactivity is available for every patient.
Main points
My question for the Authors is the following: how they explain the initial decline in antibodies titers?
Was it specific or there are other reports  looking at coexistence of  autoantibodies/autoimmune
diseases  in  HCV  patients?  For  example  in  subjects  positive  for  antithyroid  peroxidase  or  anti
thyroglobulin antibodies?
Can  we  hypothesize  that  with  a  longer  follow  up,  after  HCV  DAA-induced  eradication,  an
improvement of the underlying autoimmune disease can be expected?  Please include all comments for
the authors in this box rather than uploading your report as an attachment. Please only upload as
attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your
report which cannot be included in a text format.
Please overwrite this text when adding your comments to the authors.
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.
Unable to assess
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 manuscript or would you recommend an additional 
statistical review?
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
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 financially from the publication of this 
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially 
from the publication of this manuscript, either now 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 to 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 interests' below. If 
your reply is yes to any, please give details below.
I declare that I have not competing interests
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for 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 Access 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 included as confidential comments to the editors, which will not
be published.
I agree to the open peer review policy of the journal
assistant