Reviewer ’s report  
 
Title: The development of early ascites is associated with shorter ov erall survival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 0 Date: 01 Jan 2020  
 
Reviewer: Florian Hucke  
 
Reviewer's report:  
 
This is a well performed study analyzing prognostic factors in patients treated with DEB -TACE. 
Liver decompensation after TACE as well as history of decompens ation, higher CP stage, higher  
BCLC stage and alkaline phosphatase were independently associated with OS. The median OS 
of the study Population was 27months. However the 216 patients included in the Analysis were 
very heterogeneous - 40% of patients were BCLC A/0, most of patients were CP A but in 10% of 
patients CP stage was missing.  
 
The finding that hepatic decompensation in Terms of occurence of ascites is associated with poor 
survival has been shown several times.  
 
 
Due to the observational character o f this study and the heterogeneous Population several aspects 
should be adressed:  
 
1. A Major Question is why 40% of patients were BCLC A or even 0. Why were these patients 
not treated according to BCLC recommendations (OLT; resection, radio -frequency Abla tion)?  
 
Furthermore the Survival Analysis should be Extended to subgroups (BCLC A/0 vs BCLC B), 
since the Overall Survival was lower than those in other study.  
 
 
2. How many patients were Child B 7, 8, 9 Points? Why was CP stage not available in 20 
patients? How many patients had no Underlying liver cirrhosis? If CP stage was in fact not 
available due missing data, those patients should be excluded from further analyses.  
 
Patients with history of decompensation, CSPH and CP stage B should are a priory not reall y 
suitable patients for chemoembolisation. How many patients had those 3 characteristics? This 
should be adressed in the discussion why those patients were treated with TACE. I would like to 
see an Analysis without those patients.  
 
 
3. Patients with occurenc e of ascites after TACE 1 were retreated with TACE at the time they 
recovered. The median time between TACE1 and 2 seems very Long with 140 days. What 
happened in the meantime?  
 
4. The last follow -up was April 1 2019. Since 2017 several systemic therapies w ere approved. 
How many patients received Sorafenib? How many patients received second or third -line 
systemic therapies and which therapies?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If no t, please specify which controls are required in your comments to the authors.  
 
No 
 
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 statistics in the manu script 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 manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five year s 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 that may in a ny 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 a pplied 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 un derstan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my na med 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 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: The development of early ascites is associated with shorter ov erall survival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 0 Date: 01 Jan 2020  
 
Reviewer: Florian Hucke  
 
Reviewer's report:  
 
This is a well performed study analyzing prognostic factors in patients treated with DEB -TACE. 
Liver decompensation after TACE as well as history of decompens ation, higher CP stage, higher  
BCLC stage and alkaline phosphatase were independently associated with OS. The median OS 
of the study Population was 27months. However the 216 patients included in the Analysis were 
very heterogeneous - 40% of patients were BCLC A/0, most of patients were CP A but in 10% of 
patients CP stage was missing.  
 
The finding that hepatic decompensation in Terms of occurence of ascites is associated with poor 
survival has been shown several times.  
 
 
Due to the observational character o f this study and the heterogeneous Population several aspects 
should be adressed:  
 
1. A Major Question is why 40% of patients were BCLC A or even 0. Why were these patients 
not treated according to BCLC recommendations (OLT; resection, radio -frequency Abla tion)?  
 
Furthermore the Survival Analysis should be Extended to subgroups (BCLC A/0 vs BCLC B), 
since the Overall Survival was lower than those in other study.  
 
 
2. How many patients were Child B 7, 8, 9 Points? Why was CP stage not available in 20 
patients? How many patients had no Underlying liver cirrhosis? If CP stage was in fact not 
available due missing data, those patients should be excluded from further analyses.  
 
Patients with history of decompensation, CSPH and CP stage B should are a priory not reall y 
suitable patients for chemoembolisation. How many patients had those 3 characteristics? This 
should be adressed in the discussion why those patients were treated with TACE. I would like to 
see an Analysis without those patients.  
 
 
3. Patients with occurenc e of ascites after TACE 1 were retreated with TACE at the time they 
recovered. The median time between TACE1 and 2 seems very Long with 140 days. What 
happened in the meantime?  
 
4. The last follow -up was April 1 2019. Since 2017 several systemic therapies w ere approved. 
How many patients received Sorafenib? How many patients received second or third -line 
systemic therapies and which therapies?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If no t, please specify which controls are required in your comments to the authors.  
 
No 
 
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 statistics in the manu script 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 manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five year s 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 that may in a ny 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 a pplied 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 un derstan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my na med 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 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: The development of early ascites is associated with shorter ov erall survival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 0 Date: 01 Jan 2020  
 
Reviewer: Florian Hucke  
 
Reviewer's report:  
 
This is a well performed study analyzing prognostic factors in patients treated with DEB -TACE. 
Liver decompensation after TACE as well as history of decompens ation, higher CP stage, higher  
BCLC stage and alkaline phosphatase were independently associated with OS. The median OS 
of the study Population was 27months. However the 216 patients included in the Analysis were 
very heterogeneous - 40% of patients were BCLC A/0, most of patients were CP A but in 10% of 
patients CP stage was missing.  
 
The finding that hepatic decompensation in Terms of occurence of ascites is associated with poor 
survival has been shown several times.  
 
 
Due to the observational character o f this study and the heterogeneous Population several aspects 
should be adressed:  
 
1. A Major Question is why 40% of patients were BCLC A or even 0. Why were these patients 
not treated according to BCLC recommendations (OLT; resection, radio -frequency Abla tion)?  
 
Furthermore the Survival Analysis should be Extended to subgroups (BCLC A/0 vs BCLC B), 
since the Overall Survival was lower than those in other study.  
 
 
2. How many patients were Child B 7, 8, 9 Points? Why was CP stage not available in 20 
patients? How many patients had no Underlying liver cirrhosis? If CP stage was in fact not 
available due missing data, those patients should be excluded from further analyses.  
 
Patients with history of decompensation, CSPH and CP stage B should are a priory not reall y 
suitable patients for chemoembolisation. How many patients had those 3 characteristics? This 
should be adressed in the discussion why those patients were treated with TACE. I would like to 
see an Analysis without those patients.  
 
 
3. Patients with occurenc e of ascites after TACE 1 were retreated with TACE at the time they 
recovered. The median time between TACE1 and 2 seems very Long with 140 days. What 
happened in the meantime?  
 
4. The last follow -up was April 1 2019. Since 2017 several systemic therapies w ere approved. 
How many patients received Sorafenib? How many patients received second or third -line 
systemic therapies and which therapies?  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If no t, please specify which controls are required in your comments to the authors.  
 
No 
 
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 statistics in the manu script 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 manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five year s 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 that may in a ny 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 a pplied 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 un derstan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my na med 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 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