Reviewer ’s report  
 
Title: Hepatocellular carcinoma is the most common liver -related event in patients with 
histopathologically confirmed NAFLD in Japan  
 
Version: 1 Date: 30 Sep 2018  
 
Reviewer: Per Stål 
 
Reviewer's report:  
 
In the revised version of the manuscript "Hepatocellular carcinoma is the most common liver -
related complication in patients with histopathologically -confirmed NAFLD in Japan" by Akuta 
et al.  (BMGE -D-18-00306 -R1), the authors have dealt with the reviewers' remarks and 
comments satisfactorily. There are only a few minor commentaries regarding the revised 
manuscript, in order to enhance clarification:  
Page 7, lines 111 -113: 
I suggest that "In the present study" on  line 111 is omitted.  
On line 113 "…current HCC at the diagnosis of NAFLD" I suggest: "…existing HCC at the time 
of diagnosis of NAFLD"  
Page 7, lines 117 -119: "… current hepatic encephalopathy, esophago -gastric varices, ascites, and 
jaundice with HCC at NAFLD diagnosis, respectively. Mortality was evaluated in patients, who 
had no previous or current malignancies. Details of patient enrolment were shown in Figure 1" 
should be:  
"… current hepatic encephalopathy, esophago -gastric varices, ascites, jaundice  or HCC at the 
time of NAFLD diagnosis, respectively. Mortality was evaluated in patients, who had no 
previous or present malignancies at the time of NAFLD diagnosis. Details of patient enrolment 
are shown in Figure 1".  
Page 12, line 202:  
The sentence "In  patients with NAFLD but without previous or current malignancies.." should be 
rephrased:  
"In patients without previous or present malignancies at the time of NAFLD diagnosis…"  
Page 13, line 215: "Patients with NAFLD…" should be "We found that patients wi th NAFLD.."  
Line 220 "On the other hand…" could be omitted  
Line 225: "with no previous or current malignancies" should be "with no previous or present 
malignancies at the time of NAFLD diagnosis"  
Line 230: "The incidence oh HCC…" should be "In another study, the incidence of HCC…."  
Page 14, lines 238 -239: "…did not undergo liver biopsy…" should be "did not undergo liver 
biopsy, and were thus not included. Also, patients who visit the hospital… and  diabetes mellitus, 
which are risk factors for cardiovascular…"  
Figure legend no. 1, page 24 line 396: "The clinical details of the events of 3 patients were 
missing" is hard to understand, I suggest rephrase to: "Follow -up was missing in 3 patients".  
Line 399 I suggest: "Mortality was evaluated in 351 patients, without previous or current 
malignancies at the time of NAFLD diagnosis".  
Table 2 and Table 5, at the footer:  
"N; number of patients, without previous and current each event" is not linguisticall y correct. I 
suggest:  
"N; number of patients, not having, or having had, the respective event simultaneously or 
previously to the time of NAFLD diagnosis".  
Table 2: "**Liver -related events were evaluated in patients, without previous and current 
hepatoce llular carcinoma" should be "**Liver -related events were evaluated in patients, without 
previous or current hepatocellular carcinoma at the time of NAFLD diagnosis".  
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 st atistics 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.  
 
I am able to assess the statisti cs 
 
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 followi ng 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 st ocks 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 h ave 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 Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wis h 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 is the most common liver -related event in patients with 
histopathologically confirmed NAFLD in Japan  
 
Version: 1 Date: 30 Sep 2018  
 
Reviewer: Per Stål 
 
Reviewer's report:  
 
In the revised version of the manuscript "Hepatocellular carcinoma is the most common liver -
related complication in patients with histopathologically -confirmed NAFLD in Japan" by Akuta 
et al.  (BMGE -D-18-00306 -R1), the authors have dealt with the reviewers' remarks and 
comments satisfactorily. There are only a few minor commentaries regarding the revised 
manuscript, in order to enhance clarification:  
Page 7, lines 111 -113: 
I suggest that "In the present study" on  line 111 is omitted.  
On line 113 "…current HCC at the diagnosis of NAFLD" I suggest: "…existing HCC at the time 
of diagnosis of NAFLD"  
Page 7, lines 117 -119: "… current hepatic encephalopathy, esophago -gastric varices, ascites, and 
jaundice with HCC at NAFLD diagnosis, respectively. Mortality was evaluated in patients, who 
had no previous or current malignancies. Details of patient enrolment were shown in Figure 1" 
should be:  
"… current hepatic encephalopathy, esophago -gastric varices, ascites, jaundice  or HCC at the 
time of NAFLD diagnosis, respectively. Mortality was evaluated in patients, who had no 
previous or present malignancies at the time of NAFLD diagnosis. Details of patient enrolment 
are shown in Figure 1".  
Page 12, line 202:  
The sentence "In  patients with NAFLD but without previous or current malignancies.." should be 
rephrased:  
"In patients without previous or present malignancies at the time of NAFLD diagnosis…"  
Page 13, line 215: "Patients with NAFLD…" should be "We found that patients wi th NAFLD.."  
Line 220 "On the other hand…" could be omitted  
Line 225: "with no previous or current malignancies" should be "with no previous or present 
malignancies at the time of NAFLD diagnosis"  
Line 230: "The incidence oh HCC…" should be "In another study, the incidence of HCC…."  
Page 14, lines 238 -239: "…did not undergo liver biopsy…" should be "did not undergo liver 
biopsy, and were thus not included. Also, patients who visit the hospital… and  diabetes mellitus, 
which are risk factors for cardiovascular…"  
Figure legend no. 1, page 24 line 396: "The clinical details of the events of 3 patients were 
missing" is hard to understand, I suggest rephrase to: "Follow -up was missing in 3 patients".  
Line 399 I suggest: "Mortality was evaluated in 351 patients, without previous or current 
malignancies at the time of NAFLD diagnosis".  
Table 2 and Table 5, at the footer:  
"N; number of patients, without previous and current each event" is not linguisticall y correct. I 
suggest:  
"N; number of patients, not having, or having had, the respective event simultaneously or 
previously to the time of NAFLD diagnosis".  
Table 2: "**Liver -related events were evaluated in patients, without previous and current 
hepatoce llular carcinoma" should be "**Liver -related events were evaluated in patients, without 
previous or current hepatocellular carcinoma at the time of NAFLD diagnosis".  
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 st atistics 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.  
 
I am able to assess the statisti cs 
 
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 followi ng 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 st ocks 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 h ave 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 Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wis h 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 is the most common liver -related event in patients with 
histopathologically confirmed NAFLD in Japan  
 
Version: 1 Date: 30 Sep 2018  
 
Reviewer: Per Stål 
 
Reviewer's report:  
 
In the revised version of the manuscript "Hepatocellular carcinoma is the most common liver -
related complication in patients with histopathologically -confirmed NAFLD in Japan" by Akuta 
et al.  (BMGE -D-18-00306 -R1), the authors have dealt with the reviewers' remarks and 
comments satisfactorily. There are only a few minor commentaries regarding the revised 
manuscript, in order to enhance clarification:  
Page 7, lines 111 -113: 
I suggest that "In the present study" on  line 111 is omitted.  
On line 113 "…current HCC at the diagnosis of NAFLD" I suggest: "…existing HCC at the time 
of diagnosis of NAFLD"  
Page 7, lines 117 -119: "… current hepatic encephalopathy, esophago -gastric varices, ascites, and 
jaundice with HCC at NAFLD diagnosis, respectively. Mortality was evaluated in patients, who 
had no previous or current malignancies. Details of patient enrolment were shown in Figure 1" 
should be:  
"… current hepatic encephalopathy, esophago -gastric varices, ascites, jaundice  or HCC at the 
time of NAFLD diagnosis, respectively. Mortality was evaluated in patients, who had no 
previous or present malignancies at the time of NAFLD diagnosis. Details of patient enrolment 
are shown in Figure 1".  
Page 12, line 202:  
The sentence "In  patients with NAFLD but without previous or current malignancies.." should be 
rephrased:  
"In patients without previous or present malignancies at the time of NAFLD diagnosis…"  
Page 13, line 215: "Patients with NAFLD…" should be "We found that patients wi th NAFLD.."  
Line 220 "On the other hand…" could be omitted  
Line 225: "with no previous or current malignancies" should be "with no previous or present 
malignancies at the time of NAFLD diagnosis"  
Line 230: "The incidence oh HCC…" should be "In another study, the incidence of HCC…."  
Page 14, lines 238 -239: "…did not undergo liver biopsy…" should be "did not undergo liver 
biopsy, and were thus not included. Also, patients who visit the hospital… and  diabetes mellitus, 
which are risk factors for cardiovascular…"  
Figure legend no. 1, page 24 line 396: "The clinical details of the events of 3 patients were 
missing" is hard to understand, I suggest rephrase to: "Follow -up was missing in 3 patients".  
Line 399 I suggest: "Mortality was evaluated in 351 patients, without previous or current 
malignancies at the time of NAFLD diagnosis".  
Table 2 and Table 5, at the footer:  
"N; number of patients, without previous and current each event" is not linguisticall y correct. I 
suggest:  
"N; number of patients, not having, or having had, the respective event simultaneously or 
previously to the time of NAFLD diagnosis".  
Table 2: "**Liver -related events were evaluated in patients, without previous and current 
hepatoce llular carcinoma" should be "**Liver -related events were evaluated in patients, without 
previous or current hepatocellular carcinoma at the time of NAFLD diagnosis".  
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 st atistics 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.  
 
I am able to assess the statisti cs 
 
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 followi ng 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 st ocks 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 h ave 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 Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wis h 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