Reviewer ’s report  
Title: Case report: lactic acidosis and rhabdomyolysis during telb ivudine and tenofovir treatment 
for chroni c hepatitis B  
 
Version: 0 Date: 13 Sep 2017  
 
Reviewer: Yee Hui Yeo  
 
Reviewer's report:  
In this case report, the authors reported a case of lactic acidosis and rhabdomyolysis during 
telbivudine and tenofovir treatment for chronic hepatitis B. The case is well p resented. Several 
comments are as follow:  
 
1. The authors need to indicate if the patient has any important comorbidities such as diabetes or 
chronic kidney disease.  
2. The authors need to indicate if the patient has any concurrent drug use, any chinese herb or 
nutrition supplementary use.  
3. (page 4, row 20 -21) The authors need to present the results of other liver function test such as 
AST, bilirubin (total, indirect ) at this point, if applicable.  
4. (page 4, row 21 -22) The authors need to justify the indication for doing abdominal MRI at this 
time point. With a patient presenting neurological symptoms at lower limbs and the 
mentioned lab results, abdominal MRI is not  my first consideration.  
5. (page 5, row 2) Did the patient receive any treatment after receiving the arterial blood gas 
results?  
6. (page 5, row 3 -19) In addition to the presentation of myalgia, lab, EMG and biopsy results, the 
authors also need to menti on other urine color, urine output, and present lab results including 
electrolytes, uric acid and follow -up arterial blood gas results.  
7. (page 5, row 3 -19) The authors did not provide any clues from history taking to support the 
diagnosis of LA and RM an d to rule out other differential diagnosis. For example, any fever, 
any history of injury, any other concurrent drugs, any chinese herbs or nutrition 
supplementations...  
8. (page 6, row 2 -3) The authors should justify the change from Entecavir to tenofovir  disoproxil 
in the discussion. Is that due to the suspected resistance to Telbivudine? Any guideline that 
can support this change? etc.  
9. (page 8, row 10 -12) these clues should be moved to the clinical presentation.  
10. The authors should discuss and comp are the severe adverse events of trials that have 
investigated the efficacy and safety of Telbivudine +Tenofovir combination therapy in chronic 
hepatitis B patients. (2013, 52 -Week Efficacy and Safety of Telbivudine with Conditional 
Tenofovir Intensificati on at Week 24 in HBeAg -Positive Chronic Hepatitis B) (2014, Early 
Viral Kinetics with Telbivudine, Tenofovir or Combination of Both in Immunotolerant 
Patients with Hepatitis B e Antigen -Positive Chronic Hepatitis B)  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Unable to assess  
Does the work include the necessary controls?  
If not, ple ase 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.  
Unable to  assess  
Are you able to assess any statistics in the manuscrip t 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.  
Not relevant to this manuscript  
Quality of written Eng lish 
Please indicate the quality of language in the manuscript:  
Needs some language corrections before being published  
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, f ees, 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 tha t 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, fee s, 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 no competing interests  
 
I agree to the o pen 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 th e 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: Case report: lactic acidosis and rhabdomyolysis during telb ivudine and tenofovir treatment 
for chroni c hepatitis B  
 
Version: 0 Date: 13 Sep 2017  
 
Reviewer: Yee Hui Yeo  
 
Reviewer's report:  
In this case report, the authors reported a case of lactic acidosis and rhabdomyolysis during 
telbivudine and tenofovir treatment for chronic hepatitis B. The case is well p resented. Several 
comments are as follow:  
 
1. The authors need to indicate if the patient has any important comorbidities such as diabetes or 
chronic kidney disease.  
2. The authors need to indicate if the patient has any concurrent drug use, any chinese herb or 
nutrition supplementary use.  
3. (page 4, row 20 -21) The authors need to present the results of other liver function test such as 
AST, bilirubin (total, indirect ) at this point, if applicable.  
4. (page 4, row 21 -22) The authors need to justify the indication for doing abdominal MRI at this 
time point. With a patient presenting neurological symptoms at lower limbs and the 
mentioned lab results, abdominal MRI is not  my first consideration.  
5. (page 5, row 2) Did the patient receive any treatment after receiving the arterial blood gas 
results?  
6. (page 5, row 3 -19) In addition to the presentation of myalgia, lab, EMG and biopsy results, the 
authors also need to menti on other urine color, urine output, and present lab results including 
electrolytes, uric acid and follow -up arterial blood gas results.  
7. (page 5, row 3 -19) The authors did not provide any clues from history taking to support the 
diagnosis of LA and RM an d to rule out other differential diagnosis. For example, any fever, 
any history of injury, any other concurrent drugs, any chinese herbs or nutrition 
supplementations...  
8. (page 6, row 2 -3) The authors should justify the change from Entecavir to tenofovir  disoproxil 
in the discussion. Is that due to the suspected resistance to Telbivudine? Any guideline that 
can support this change? etc.  
9. (page 8, row 10 -12) these clues should be moved to the clinical presentation.  
10. The authors should discuss and comp are the severe adverse events of trials that have 
investigated the efficacy and safety of Telbivudine +Tenofovir combination therapy in chronic 
hepatitis B patients. (2013, 52 -Week Efficacy and Safety of Telbivudine with Conditional 
Tenofovir Intensificati on at Week 24 in HBeAg -Positive Chronic Hepatitis B) (2014, Early 
Viral Kinetics with Telbivudine, Tenofovir or Combination of Both in Immunotolerant 
Patients with Hepatitis B e Antigen -Positive Chronic Hepatitis B)  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Unable to assess  
Does the work include the necessary controls?  
If not, ple ase 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.  
Unable to  assess  
Are you able to assess any statistics in the manuscrip t 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.  
Not relevant to this manuscript  
Quality of written Eng lish 
Please indicate the quality of language in the manuscript:  
Needs some language corrections before being published  
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, f ees, 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 tha t 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, fee s, 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 no competing interests  
 
I agree to the o pen 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 th e 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: Case report: lactic acidosis and rhabdomyolysis during telb ivudine and tenofovir treatment 
for chroni c hepatitis B  
 
Version: 0 Date: 13 Sep 2017  
 
Reviewer: Yee Hui Yeo  
 
Reviewer's report:  
In this case report, the authors reported a case of lactic acidosis and rhabdomyolysis during 
telbivudine and tenofovir treatment for chronic hepatitis B. The case is well p resented. Several 
comments are as follow:  
 
1. The authors need to indicate if the patient has any important comorbidities such as diabetes or 
chronic kidney disease.  
2. The authors need to indicate if the patient has any concurrent drug use, any chinese herb or 
nutrition supplementary use.  
3. (page 4, row 20 -21) The authors need to present the results of other liver function test such as 
AST, bilirubin (total, indirect ) at this point, if applicable.  
4. (page 4, row 21 -22) The authors need to justify the indication for doing abdominal MRI at this 
time point. With a patient presenting neurological symptoms at lower limbs and the 
mentioned lab results, abdominal MRI is not  my first consideration.  
5. (page 5, row 2) Did the patient receive any treatment after receiving the arterial blood gas 
results?  
6. (page 5, row 3 -19) In addition to the presentation of myalgia, lab, EMG and biopsy results, the 
authors also need to menti on other urine color, urine output, and present lab results including 
electrolytes, uric acid and follow -up arterial blood gas results.  
7. (page 5, row 3 -19) The authors did not provide any clues from history taking to support the 
diagnosis of LA and RM an d to rule out other differential diagnosis. For example, any fever, 
any history of injury, any other concurrent drugs, any chinese herbs or nutrition 
supplementations...  
8. (page 6, row 2 -3) The authors should justify the change from Entecavir to tenofovir  disoproxil 
in the discussion. Is that due to the suspected resistance to Telbivudine? Any guideline that 
can support this change? etc.  
9. (page 8, row 10 -12) these clues should be moved to the clinical presentation.  
10. The authors should discuss and comp are the severe adverse events of trials that have 
investigated the efficacy and safety of Telbivudine +Tenofovir combination therapy in chronic 
hepatitis B patients. (2013, 52 -Week Efficacy and Safety of Telbivudine with Conditional 
Tenofovir Intensificati on at Week 24 in HBeAg -Positive Chronic Hepatitis B) (2014, Early 
Viral Kinetics with Telbivudine, Tenofovir or Combination of Both in Immunotolerant 
Patients with Hepatitis B e Antigen -Positive Chronic Hepatitis B)  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Unable to assess  
Does the work include the necessary controls?  
If not, ple ase 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.  
Unable to  assess  
Are you able to assess any statistics in the manuscrip t 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.  
Not relevant to this manuscript  
Quality of written Eng lish 
Please indicate the quality of language in the manuscript:  
Needs some language corrections before being published  
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, f ees, 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 tha t 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, fee s, 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 no competing interests  
 
I agree to the o pen 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 th e 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