Reviewer ’s report  
 
Title: Comparison of the Prevalence, Severity, and R isk Factors for Hepatic Steatosis in HIV -
Infected and Uninfected People  
 
Version: 0 Date: 11 Sep 2018  
 
Reviewer: Phunchai Charatcharoenwitthaya  
 
Reviewer's report:  
 
Torgersen et al conducted a cross -sectional study among participants without cardiovascular 
disease who participated in the Veterans Aging Cohort Study. They reported the prevalence and 
severity of hepatic steatosis among 171 HIV -infected and 97 uninfected  persons and identified 
factors associated with greater steatosis severity within both groups. The prevalence of hepatic 
steatosis by noncontrast abdominal CT was not different by HIV status. Increasing severity of 
liver steatosis was independently associa ted with advanced liver fibrosis in both groups.   
Comments to the Author  
Hepatic steatosis has emerged as a potential contributor to liver fibrosis progression in HIV -
infected people. Several studies have examined the prevalence, clinical presentation and  risk 
factors of steatosis in HIV infection. However, several data on this topic have been published 
previously and some issues should be addressed:  
1. The authors should clearly comment on the exclusion criteria of cardiovascular disease 
for the study pop ulation. What is the hypothesis for this criterion? This should lead to the 
different prevalence and risk factors of hepatic steatosis when compared to previous studies.  
2. What is the flow of enrollment of patients into this study? What is the attrition rate of this 
study? Selection bias could lead to the different results of each prevalence study. Healthy 
veterans may be more likely to participate into the study.  
3. In this small -sample size of veterans mainly Black/African American ethnicity during 
2008 -2011, the overall prevalence of steatosis was 8.2% in uninfected individuals. This rate was 
lower than age -adjusted prevalence of 17.6% in 2011 from a US Cohort of Veterans reported by 
Kanwal et al in Clinical Gastroenterology and Hepatology 2016. This di fferent data deserves a 
comment.  
4. Almost of HIV -infected patients have been on ART with median CD4 count 492 
cells/mm3 and, 90% of them had an undetectable HIV RNA. This indicates that this study could 
not evaluate the effect of HIV infection on the ris k of hepatic steatosis. On the other hand, the 
potential impact of antiretroviral therapy on the emergence of steatosis needs to be explored in 
this population.  
5. Metabolic derangement and the development of lipodystrophy have been demonstrated to 
be ass ociated with many different antiretroviral therapy and HIV itself. However, in this study, 
HIV-infected patients has a lower proportion of obesity (BMI>30 kg/m2; 14% vs. 34%, 
p=0.007) and similar prevalence of diabetes (19% vs. 20%, p=0.95) and hypertensio n (82% vs. 
83%, p=0.77) compared to uninfected patients. What is the explanation for this discrepant 
observation?  
6. The diagnostic accuracy of FIB -4 score is unreliable for the assessment of liver fibrosis. 
The authors should evaluate other non -invasive tools, such as NAFLD fibrosis score or serum -
based algorithm in this study.  
7. Given advanced liver fibrosis in nonalcoholic steatohepatitis is often accompanied by a 
reduction in hepatic fat to the point of complete fat loss (burnt -out NASH), it is surpr isingly that 
increasing severity of steatosis was associated with advanced hepatic fibrosis as measured by 
FIB-4 in both HIV+ and uninfected persons. These different data deserve a comment.  
 
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 not, 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 manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects requ ire 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, 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 fut ure? 
 
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 acce pted 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 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: Comparison of the Prevalence, Severity, and R isk Factors for Hepatic Steatosis in HIV -
Infected and Uninfected People  
 
Version: 0 Date: 11 Sep 2018  
 
Reviewer: Phunchai Charatcharoenwitthaya  
 
Reviewer's report:  
 
Torgersen et al conducted a cross -sectional study among participants without cardiovascular 
disease who participated in the Veterans Aging Cohort Study. They reported the prevalence and 
severity of hepatic steatosis among 171 HIV -infected and 97 uninfected  persons and identified 
factors associated with greater steatosis severity within both groups. The prevalence of hepatic 
steatosis by noncontrast abdominal CT was not different by HIV status. Increasing severity of 
liver steatosis was independently associa ted with advanced liver fibrosis in both groups.   
Comments to the Author  
Hepatic steatosis has emerged as a potential contributor to liver fibrosis progression in HIV -
infected people. Several studies have examined the prevalence, clinical presentation and  risk 
factors of steatosis in HIV infection. However, several data on this topic have been published 
previously and some issues should be addressed:  
1. The authors should clearly comment on the exclusion criteria of cardiovascular disease 
for the study pop ulation. What is the hypothesis for this criterion? This should lead to the 
different prevalence and risk factors of hepatic steatosis when compared to previous studies.  
2. What is the flow of enrollment of patients into this study? What is the attrition rate of this 
study? Selection bias could lead to the different results of each prevalence study. Healthy 
veterans may be more likely to participate into the study.  
3. In this small -sample size of veterans mainly Black/African American ethnicity during 
2008 -2011, the overall prevalence of steatosis was 8.2% in uninfected individuals. This rate was 
lower than age -adjusted prevalence of 17.6% in 2011 from a US Cohort of Veterans reported by 
Kanwal et al in Clinical Gastroenterology and Hepatology 2016. This di fferent data deserves a 
comment.  
4. Almost of HIV -infected patients have been on ART with median CD4 count 492 
cells/mm3 and, 90% of them had an undetectable HIV RNA. This indicates that this study could 
not evaluate the effect of HIV infection on the ris k of hepatic steatosis. On the other hand, the 
potential impact of antiretroviral therapy on the emergence of steatosis needs to be explored in 
this population.  
5. Metabolic derangement and the development of lipodystrophy have been demonstrated to 
be ass ociated with many different antiretroviral therapy and HIV itself. However, in this study, 
HIV-infected patients has a lower proportion of obesity (BMI>30 kg/m2; 14% vs. 34%, 
p=0.007) and similar prevalence of diabetes (19% vs. 20%, p=0.95) and hypertensio n (82% vs. 
83%, p=0.77) compared to uninfected patients. What is the explanation for this discrepant 
observation?  
6. The diagnostic accuracy of FIB -4 score is unreliable for the assessment of liver fibrosis. 
The authors should evaluate other non -invasive tools, such as NAFLD fibrosis score or serum -
based algorithm in this study.  
7. Given advanced liver fibrosis in nonalcoholic steatohepatitis is often accompanied by a 
reduction in hepatic fat to the point of complete fat loss (burnt -out NASH), it is surpr isingly that 
increasing severity of steatosis was associated with advanced hepatic fibrosis as measured by 
FIB-4 in both HIV+ and uninfected persons. These different data deserve a comment.  
 
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 not, 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 manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects requ ire 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, 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 fut ure? 
 
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 acce pted 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 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: Comparison of the Prevalence, Severity, and R isk Factors for Hepatic Steatosis in HIV -
Infected and Uninfected People  
 
Version: 0 Date: 11 Sep 2018  
 
Reviewer: Phunchai Charatcharoenwitthaya  
 
Reviewer's report:  
 
Torgersen et al conducted a cross -sectional study among participants without cardiovascular 
disease who participated in the Veterans Aging Cohort Study. They reported the prevalence and 
severity of hepatic steatosis among 171 HIV -infected and 97 uninfected  persons and identified 
factors associated with greater steatosis severity within both groups. The prevalence of hepatic 
steatosis by noncontrast abdominal CT was not different by HIV status. Increasing severity of 
liver steatosis was independently associa ted with advanced liver fibrosis in both groups.   
Comments to the Author  
Hepatic steatosis has emerged as a potential contributor to liver fibrosis progression in HIV -
infected people. Several studies have examined the prevalence, clinical presentation and  risk 
factors of steatosis in HIV infection. However, several data on this topic have been published 
previously and some issues should be addressed:  
1. The authors should clearly comment on the exclusion criteria of cardiovascular disease 
for the study pop ulation. What is the hypothesis for this criterion? This should lead to the 
different prevalence and risk factors of hepatic steatosis when compared to previous studies.  
2. What is the flow of enrollment of patients into this study? What is the attrition rate of this 
study? Selection bias could lead to the different results of each prevalence study. Healthy 
veterans may be more likely to participate into the study.  
3. In this small -sample size of veterans mainly Black/African American ethnicity during 
2008 -2011, the overall prevalence of steatosis was 8.2% in uninfected individuals. This rate was 
lower than age -adjusted prevalence of 17.6% in 2011 from a US Cohort of Veterans reported by 
Kanwal et al in Clinical Gastroenterology and Hepatology 2016. This di fferent data deserves a 
comment.  
4. Almost of HIV -infected patients have been on ART with median CD4 count 492 
cells/mm3 and, 90% of them had an undetectable HIV RNA. This indicates that this study could 
not evaluate the effect of HIV infection on the ris k of hepatic steatosis. On the other hand, the 
potential impact of antiretroviral therapy on the emergence of steatosis needs to be explored in 
this population.  
5. Metabolic derangement and the development of lipodystrophy have been demonstrated to 
be ass ociated with many different antiretroviral therapy and HIV itself. However, in this study, 
HIV-infected patients has a lower proportion of obesity (BMI>30 kg/m2; 14% vs. 34%, 
p=0.007) and similar prevalence of diabetes (19% vs. 20%, p=0.95) and hypertensio n (82% vs. 
83%, p=0.77) compared to uninfected patients. What is the explanation for this discrepant 
observation?  
6. The diagnostic accuracy of FIB -4 score is unreliable for the assessment of liver fibrosis. 
The authors should evaluate other non -invasive tools, such as NAFLD fibrosis score or serum -
based algorithm in this study.  
7. Given advanced liver fibrosis in nonalcoholic steatohepatitis is often accompanied by a 
reduction in hepatic fat to the point of complete fat loss (burnt -out NASH), it is surpr isingly that 
increasing severity of steatosis was associated with advanced hepatic fibrosis as measured by 
FIB-4 in both HIV+ and uninfected persons. These different data deserve a comment.  
 
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 not, 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 manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects requ ire 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, 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 fut ure? 
 
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 acce pted 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 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