Reviewer ’s report  
 
Title: Nomogram based on blood lipoprotein for estimation of mortality in patients with hepatitis  
B virus -related acute -on-chronic liver failure  
 
Version: 0 Date: 04 Oct 2019  
 
Reviewer: Jian-Ming Zheng  
 
Reviewer's report:  
 
Comments to the Author  
The study tried to formulate and validate a nomogram model based on blood lipoprotein for 
prediction of 3 -month mortality in patients with hepatitis B virus (HBV) -related ACLF. It is a 
retrospective controlled study, not a randomized controlled study. In this study, 393 consecutive 
patients with HBV -related ACLF were retrospectively reviewed. 260 patients who were 
collected in an earlier period formed the training cohort for the development of nomogram, while 
133 patients who were collected thereafter formed the validation cohort for confirming the 
performance of nomogram.  
 
 
 
MAJOR COMMENTS  
 
1. The patients' inclusion criteria has some problems. The consensus recommendations of the 
Asian Pacific  Association for the Study of the Liver (APASL) 2014 for ACLF were used as the 
diagnostic criteria in this study. However, the patients' inclusion criteria in the methods are 
different from the APASL 2014 consensus recommendations. Such as, one of the incl usion 
criteria is "serum total bilirubin (TBIL) level &gt; 10 times of the normal level, i.e., TBIL ≥85 
μmol/L)". But the diagnostic criteria of APASL 2014 for ACLF is that the original value of ≥5 
mg/dl (5 times of the normal level) was accepted as the cu toff for bilirubin for defining liver 
failure. The second of the inclusion criteria is a history of liver cirrhosis. That is different from 
APASL 2014 diagnostic criteria. The APASL 2014 concept of ACLF is defined as a proportion 
of patients who present wi th features mimicking ALF, however, have an underlying chronic liver 
disease or cirrhosis of the liver. Both cirrhotic and non -cirrhotic chronic liver diseases qualify as 
chronic liver diseases. The coagulopathy of liver failure is defined as prothrombin a ctivity &lt; 
40% of the normal level in the article, but the coagulopathy of APASL 2014 ACLF diagnostic 
criteria is defined by INR, not PTA.  
 
2. INR not showed in the data, but The MELD score was computed using INR as a lab 
parameter.  
 
3. ROC curve (receiver  operating characteristic curve) may be used to compare the prediction of 
nomogram scores with that of MELD scores.  
 
4. Why define low level LDLC is 0.5, middle level LDLC is 0.5 to 1, high level of LDLC is 
above 1?  
 
5. Does other parameters affect prognosis , such as sodium, HBeAg status, HBV DNA level or 
antiviral drug?  
 
6. The conclusions of this study is that reduction of serum LDLC level was an independent risk 
factor for the survival in patients with HBV -related ACLF, and the nomogram based on serum 
LDLC was an accurate and practical model for predicting the 3 -month mortality in patients with 
this disease. Whether nomogram score is better than MELD score for predicting the 3 -month 
mortality in patients with HBV -related ACLF?  
 
7. Discussions were inadequate and similar researches were not mentioned.(such as, Etogo -Asse 
FE et al. High density lipoprotein in patients with liver failure; relation to sepsis, adrenal 
function and outcome of illness. Liver Int. 2012 Jan;32(1):128 -36. Manka P et al. Low levels of 
blood lipids are associated with etiology and lethal outcome in acute liver failure. PLoS One. 
2014 Jul 15;9(7):e102351.)  
 
 
 
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 necess ary 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.  
 
No 
 
Are you able to assess any st atistics 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 recommend additional statistical review  
 
Quality of written English  
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 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 now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content o f 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 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 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 i n 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: Nomogram based on blood lipoprotein for estimation of mortality in patients with hepatitis  
B virus -related acute -on-chronic liver failure  
 
Version: 0 Date: 04 Oct 2019  
 
Reviewer: Jian-Ming Zheng  
 
Reviewer's report:  
 
Comments to the Author  
The study tried to formulate and validate a nomogram model based on blood lipoprotein for 
prediction of 3 -month mortality in patients with hepatitis B virus (HBV) -related ACLF. It is a 
retrospective controlled study, not a randomized controlled study. In this study, 393 consecutive 
patients with HBV -related ACLF were retrospectively reviewed. 260 patients who were 
collected in an earlier period formed the training cohort for the development of nomogram, while 
133 patients who were collected thereafter formed the validation cohort for confirming the 
performance of nomogram.  
 
 
 
MAJOR COMMENTS  
 
1. The patients' inclusion criteria has some problems. The consensus recommendations of the 
Asian Pacific  Association for the Study of the Liver (APASL) 2014 for ACLF were used as the 
diagnostic criteria in this study. However, the patients' inclusion criteria in the methods are 
different from the APASL 2014 consensus recommendations. Such as, one of the incl usion 
criteria is "serum total bilirubin (TBIL) level &gt; 10 times of the normal level, i.e., TBIL ≥85 
μmol/L)". But the diagnostic criteria of APASL 2014 for ACLF is that the original value of ≥5 
mg/dl (5 times of the normal level) was accepted as the cu toff for bilirubin for defining liver 
failure. The second of the inclusion criteria is a history of liver cirrhosis. That is different from 
APASL 2014 diagnostic criteria. The APASL 2014 concept of ACLF is defined as a proportion 
of patients who present wi th features mimicking ALF, however, have an underlying chronic liver 
disease or cirrhosis of the liver. Both cirrhotic and non -cirrhotic chronic liver diseases qualify as 
chronic liver diseases. The coagulopathy of liver failure is defined as prothrombin a ctivity &lt; 
40% of the normal level in the article, but the coagulopathy of APASL 2014 ACLF diagnostic 
criteria is defined by INR, not PTA.  
 
2. INR not showed in the data, but The MELD score was computed using INR as a lab 
parameter.  
 
3. ROC curve (receiver  operating characteristic curve) may be used to compare the prediction of 
nomogram scores with that of MELD scores.  
 
4. Why define low level LDLC is 0.5, middle level LDLC is 0.5 to 1, high level of LDLC is 
above 1?  
 
5. Does other parameters affect prognosis , such as sodium, HBeAg status, HBV DNA level or 
antiviral drug?  
 
6. The conclusions of this study is that reduction of serum LDLC level was an independent risk 
factor for the survival in patients with HBV -related ACLF, and the nomogram based on serum 
LDLC was an accurate and practical model for predicting the 3 -month mortality in patients with 
this disease. Whether nomogram score is better than MELD score for predicting the 3 -month 
mortality in patients with HBV -related ACLF?  
 
7. Discussions were inadequate and similar researches were not mentioned.(such as, Etogo -Asse 
FE et al. High density lipoprotein in patients with liver failure; relation to sepsis, adrenal 
function and outcome of illness. Liver Int. 2012 Jan;32(1):128 -36. Manka P et al. Low levels of 
blood lipids are associated with etiology and lethal outcome in acute liver failure. PLoS One. 
2014 Jul 15;9(7):e102351.)  
 
 
 
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 necess ary 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.  
 
No 
 
Are you able to assess any st atistics 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 recommend additional statistical review  
 
Quality of written English  
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 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 now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content o f 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 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 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 i n 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: Nomogram based on blood lipoprotein for estimation of mortality in patients with hepatitis  
B virus -related acute -on-chronic liver failure  
 
Version: 0 Date: 04 Oct 2019  
 
Reviewer: Jian-Ming Zheng  
 
Reviewer's report:  
 
Comments to the Author  
The study tried to formulate and validate a nomogram model based on blood lipoprotein for 
prediction of 3 -month mortality in patients with hepatitis B virus (HBV) -related ACLF. It is a 
retrospective controlled study, not a randomized controlled study. In this study, 393 consecutive 
patients with HBV -related ACLF were retrospectively reviewed. 260 patients who were 
collected in an earlier period formed the training cohort for the development of nomogram, while 
133 patients who were collected thereafter formed the validation cohort for confirming the 
performance of nomogram.  
 
 
 
MAJOR COMMENTS  
 
1. The patients' inclusion criteria has some problems. The consensus recommendations of the 
Asian Pacific  Association for the Study of the Liver (APASL) 2014 for ACLF were used as the 
diagnostic criteria in this study. However, the patients' inclusion criteria in the methods are 
different from the APASL 2014 consensus recommendations. Such as, one of the incl usion 
criteria is "serum total bilirubin (TBIL) level &gt; 10 times of the normal level, i.e., TBIL ≥85 
μmol/L)". But the diagnostic criteria of APASL 2014 for ACLF is that the original value of ≥5 
mg/dl (5 times of the normal level) was accepted as the cu toff for bilirubin for defining liver 
failure. The second of the inclusion criteria is a history of liver cirrhosis. That is different from 
APASL 2014 diagnostic criteria. The APASL 2014 concept of ACLF is defined as a proportion 
of patients who present wi th features mimicking ALF, however, have an underlying chronic liver 
disease or cirrhosis of the liver. Both cirrhotic and non -cirrhotic chronic liver diseases qualify as 
chronic liver diseases. The coagulopathy of liver failure is defined as prothrombin a ctivity &lt; 
40% of the normal level in the article, but the coagulopathy of APASL 2014 ACLF diagnostic 
criteria is defined by INR, not PTA.  
 
2. INR not showed in the data, but The MELD score was computed using INR as a lab 
parameter.  
 
3. ROC curve (receiver  operating characteristic curve) may be used to compare the prediction of 
nomogram scores with that of MELD scores.  
 
4. Why define low level LDLC is 0.5, middle level LDLC is 0.5 to 1, high level of LDLC is 
above 1?  
 
5. Does other parameters affect prognosis , such as sodium, HBeAg status, HBV DNA level or 
antiviral drug?  
 
6. The conclusions of this study is that reduction of serum LDLC level was an independent risk 
factor for the survival in patients with HBV -related ACLF, and the nomogram based on serum 
LDLC was an accurate and practical model for predicting the 3 -month mortality in patients with 
this disease. Whether nomogram score is better than MELD score for predicting the 3 -month 
mortality in patients with HBV -related ACLF?  
 
7. Discussions were inadequate and similar researches were not mentioned.(such as, Etogo -Asse 
FE et al. High density lipoprotein in patients with liver failure; relation to sepsis, adrenal 
function and outcome of illness. Liver Int. 2012 Jan;32(1):128 -36. Manka P et al. Low levels of 
blood lipids are associated with etiology and lethal outcome in acute liver failure. PLoS One. 
2014 Jul 15;9(7):e102351.)  
 
 
 
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 necess ary 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.  
 
No 
 
Are you able to assess any st atistics 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 recommend additional statistical review  
 
Quality of written English  
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 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 now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content o f 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 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 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 i n 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