Reviewer ’s report  
 
Title: Hepatocellular carcinoma in Adult Thalassemia patients: An expert opinion based on  
current evidence  
 
Version: 0 Date: 15 Apr 2020  
 
Reviewer's report:  
 
I read with interest the submitted paper entitled "HCC in Adult Thalassemia patients: An expert 
opinion based on current evidence".  
Overall, the p aper tries to translate into clinical indications, the scanty evidence about HCC in 
thalassemia (TH).  
However, who has clinical experience in rare diseases knows how frequently published data 
lacks when one has to take clinical decisions.  
Furthermore, abou t HCC in thalassemia, very few are the known experts and concentrated in the 
areas were TH is endemic.  
Consequently, whether the report of published studies is satisfactory (albeit not complete), some 
of the statements are in my opinion not agreable.  
 
My m ain coniderations are the following:  
 
-Background, First page, Line 52 - 59: 
The risk of HCC in TH is generally due to a combination of factors, as reported in the text, and 
has been increasing since the wide use of iron chelation, as a consequence of over all improved 
TH outcome. Then, HCC incidence in TH will likely increase in next future.  
 
-Background, Second page, Line 2:  
Who has clinical experience of the tahalassemia setting knows that rate of TI is absolutely 
greater than 10% of total TH.  
 
Main body  
-Statement 1 is not agreable. In fact, while the scanty studies on HCC incidence in TH report 
similar rate than in non thalassemics, mean age is absolutely younger in TH: this means that the 
risk of HCC in TH is probably higher.  
 
-Statement 6:  
US surveillance of HCC in TH is agreable but there are not enough data to suggest routine MRI.  
 
-Page 18, Line 8 - 13 and statement 8:  
Choice of HCC treatment in TH must consider comorbididies associated to TH, maily overt or 
subclinical heart failure (HF)  or pulmonary hypertension (PH).  
 
-Statement 9: agreable, provided that severe PH and indolent HF are excluded.  
  
-Statement 10 is not agreable because of lack of evidence: only one heart -liver transplant in TH 
and without long term data published.  
 
-State ment 12: agreable but cosider the possibility of drug interections.  
 
 
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, 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 no 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 Acces s 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: Hepatocellular carcinoma in Adult Thalassemia patients: An expert opinion based on  
current evidence  
 
Version: 0 Date: 15 Apr 2020  
 
Reviewer's report:  
 
I read with interest the submitted paper entitled "HCC in Adult Thalassemia patients: An expert 
opinion based on current evidence".  
Overall, the p aper tries to translate into clinical indications, the scanty evidence about HCC in 
thalassemia (TH).  
However, who has clinical experience in rare diseases knows how frequently published data 
lacks when one has to take clinical decisions.  
Furthermore, abou t HCC in thalassemia, very few are the known experts and concentrated in the 
areas were TH is endemic.  
Consequently, whether the report of published studies is satisfactory (albeit not complete), some 
of the statements are in my opinion not agreable.  
 
My m ain coniderations are the following:  
 
-Background, First page, Line 52 - 59: 
The risk of HCC in TH is generally due to a combination of factors, as reported in the text, and 
has been increasing since the wide use of iron chelation, as a consequence of over all improved 
TH outcome. Then, HCC incidence in TH will likely increase in next future.  
 
-Background, Second page, Line 2:  
Who has clinical experience of the tahalassemia setting knows that rate of TI is absolutely 
greater than 10% of total TH.  
 
Main body  
-Statement 1 is not agreable. In fact, while the scanty studies on HCC incidence in TH report 
similar rate than in non thalassemics, mean age is absolutely younger in TH: this means that the 
risk of HCC in TH is probably higher.  
 
-Statement 6:  
US surveillance of HCC in TH is agreable but there are not enough data to suggest routine MRI.  
 
-Page 18, Line 8 - 13 and statement 8:  
Choice of HCC treatment in TH must consider comorbididies associated to TH, maily overt or 
subclinical heart failure (HF)  or pulmonary hypertension (PH).  
 
-Statement 9: agreable, provided that severe PH and indolent HF are excluded.  
  
-Statement 10 is not agreable because of lack of evidence: only one heart -liver transplant in TH 
and without long term data published.  
 
-State ment 12: agreable but cosider the possibility of drug interections.  
 
 
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, 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 no 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 Acces s 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: Hepatocellular carcinoma in Adult Thalassemia patients: An expert opinion based on  
current evidence  
 
Version: 0 Date: 15 Apr 2020  
 
Reviewer's report:  
 
I read with interest the submitted paper entitled "HCC in Adult Thalassemia patients: An expert 
opinion based on current evidence".  
Overall, the p aper tries to translate into clinical indications, the scanty evidence about HCC in 
thalassemia (TH).  
However, who has clinical experience in rare diseases knows how frequently published data 
lacks when one has to take clinical decisions.  
Furthermore, abou t HCC in thalassemia, very few are the known experts and concentrated in the 
areas were TH is endemic.  
Consequently, whether the report of published studies is satisfactory (albeit not complete), some 
of the statements are in my opinion not agreable.  
 
My m ain coniderations are the following:  
 
-Background, First page, Line 52 - 59: 
The risk of HCC in TH is generally due to a combination of factors, as reported in the text, and 
has been increasing since the wide use of iron chelation, as a consequence of over all improved 
TH outcome. Then, HCC incidence in TH will likely increase in next future.  
 
-Background, Second page, Line 2:  
Who has clinical experience of the tahalassemia setting knows that rate of TI is absolutely 
greater than 10% of total TH.  
 
Main body  
-Statement 1 is not agreable. In fact, while the scanty studies on HCC incidence in TH report 
similar rate than in non thalassemics, mean age is absolutely younger in TH: this means that the 
risk of HCC in TH is probably higher.  
 
-Statement 6:  
US surveillance of HCC in TH is agreable but there are not enough data to suggest routine MRI.  
 
-Page 18, Line 8 - 13 and statement 8:  
Choice of HCC treatment in TH must consider comorbididies associated to TH, maily overt or 
subclinical heart failure (HF)  or pulmonary hypertension (PH).  
 
-Statement 9: agreable, provided that severe PH and indolent HF are excluded.  
  
-Statement 10 is not agreable because of lack of evidence: only one heart -liver transplant in TH 
and without long term data published.  
 
-State ment 12: agreable but cosider the possibility of drug interections.  
 
 
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, 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 no 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 Acces s 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