Title: Clinical Characteristics and Management of Patients with Nonalcoholic Steatohepatitis
in a Real-World Setting: Analysis of the Ipsos NASH Therapy Monitor Database
Version: 2 Date: 24 Jan 2023
Reviewer's report:
GENERAL COMMENTS.
This cross-sectional database study  in USA provides two "snapshots", in late 2016 and in late
2017, of patients assigned a clinical diagnosis of NASH, irrespective of diagnostic method.
It sought to assess the demographic and clinical characteristics of patients according to their
fibrosis stage and also to understand the diagnostic testing  and treatment regimes by fibrosis
stage, physician specialty and ethnicity in a real-world, but specifically not an academic US
medical center.
In reviewing any paper to assess its potential value to the medical literature, I look to see the
nature of any new findings ,  how it might compare to other evidence from other relevant studies,
any limitations and the potential impact of said new findings.
Essentially using this criteria I did not find much new which could influence clinical practice
that has not been voiced in other publications.  It did raise some questions which could merit
further exploration in future studies in order to address them. There was a lot of data, some not
utilized, and there were some inconsistencies in the paper. The cited references were very US
centric and  could and should have drawn upon other relevant publications from other countries,
potentially allowing the authors opportunities to compare their findings with others (who found
similar observations and offered similar 'ways forward' in general).  A few statements in the
paper required the addition of a reference.
SOME  SPECIFIC COMMENTS
Abstract
This study assesses   treatment regimes rather than management of patients NASH management
- that is a broader remit
Some of the numbers of patients with F stages are inconsistent with Table 2.
Plain language summary
Table 2 states that over 2% patients were of F stage unknown. Inconsistencies between text and
tables.
Background.
Lines 82-3. Please add a reference for the statement "The severity of liver fibrosis.......and
protective factors."
Cited reference 7 could be embellished with other recent SLRs in this space.
Methods:
Table 1 described study attrition of patients who had been diagnosed NASH by the contributing
physicians  documenting the final sample.  I looked at the  numbers excluded and calculated
attrition rates as  follows:   ALL (n=777 or 24.7%), PCPs  (n=78 or 35%), Gastroenterologists
(n=317 or 21%), Hepatologists (n=87 or 10.6%) and endocrinologists (n=295 or 48.4%), This
was not shown in the Table 1 or commented upon. I would suggest this is of note for physicians
who state "they manage at least 20 NASH patients per month". The study aims to describe non-
academic center management by specialty after all.
Study measures.  You state that data was collected regarding patient experiences with NASH
diagnosis and treatment.  Was this physician or patient basis. I missed this in the paper.
Results:
Patient demographics by ethnicity -
Line 166. You state between 61% and 69% of patients were currently employed.  Patients with
F4 Fibrosis stage in Table 2 were 40% employed. Severe NASH impacts work-life balance and
QOL. This should be highlighted.
There are inconsistencies between text and Figures 1 and 2. Also there are (I believe)
inconsistencies between Figure 1 and 2A.
Figure 1 & 2A.
Table 2 describes of the whole study group (n=2,366) there were 189 patients with F0 in the
study.  Figure 1 and 2A  describe  234 patients with F0. Please correct.
Despite having the same denominators per F stage.
Discussion.
Liver biopsy remains the standard for NASH diagnosis and F staging. This study acknowledges
the (unexpected) high proportion of patients having undergone a liver biopsy across these
participating physicians. And more could perhaps be made of this observation by revisiting these
centers or importantly by updating this (as the authors acknowledge) 6-7 year old data collected
in 2016 and 2017.  Citing research in other jurisdictions would validate this point, namely of
low use of liver biopsies.  It could also suggest the participating physicians in this study  are as
'expert' as those in US academic centers of course.  The eligibility of participating patients here
is not dissimilar to other Real World studies elsewhere outside USA.
Line 259-262. What is the reference supporting the sentence: "Despite the well
documented...........stage of fibrosis in this analysis."
Line 262-263. What is the reference to support the sentence: "It  is possible that there is....with
genotype offset."
Lines 283-288. Currently, in the absence of treatments indicated for the treatment of NASH,
pharmacological treatments prescribed by  clinicians/specialists worldwide  are prescribed to
control the underlying risk factors of NASH (i.e. T2D, obesity) and this study endorses these
observations. Citing other researchers work would be expected here.  Their conclusions were
almost identical.
Limitations.
The authors rightly acknowledge the age of the data in the study.  It would be optimal to repeat
this exercise to see the current state of affairs.  Or at a minimum look to see if 2016 vs 2017
were the same or exhibited trends of change?  Perhaps there are too many variables.
Discussion.
A number of the suggestions posed in the discussion suggest the participating physicians are
specialized experts and that the management is not dissimilar to 'academic centers'
Lines 259-263. What are the references supporting the statements spanning the text: "Despite
the well documented.......high-risk nutrients with genotype offset".. I do not understand this.
Title: Clinical Characteristics and Management of Patients with Nonalcoholic Steatohepatitis
in a Real-World Setting: Analysis of the Ipsos NASH Therapy Monitor Database
Version: 2 Date: 24 Jan 2023
Reviewer's report:
GENERAL COMMENTS.
This cross-sectional database study  in USA provides two "snapshots", in late 2016 and in late
2017, of patients assigned a clinical diagnosis of NASH, irrespective of diagnostic method.
It sought to assess the demographic and clinical characteristics of patients according to their
fibrosis stage and also to understand the diagnostic testing  and treatment regimes by fibrosis
stage, physician specialty and ethnicity in a real-world, but specifically not an academic US
medical center.
In reviewing any paper to assess its potential value to the medical literature, I look to see the
nature of any new findings ,  how it might compare to other evidence from other relevant studies,
any limitations and the potential impact of said new findings.
Essentially using this criteria I did not find much new which could influence clinical practice
that has not been voiced in other publications.  It did raise some questions which could merit
further exploration in future studies in order to address them. There was a lot of data, some not
utilized, and there were some inconsistencies in the paper. The cited references were very US
centric and  could and should have drawn upon other relevant publications from other countries,
potentially allowing the authors opportunities to compare their findings with others (who found
similar observations and offered similar 'ways forward' in general).  A few statements in the
paper required the addition of a reference.
SOME  SPECIFIC COMMENTS
Abstract
This study assesses   treatment regimes rather than management of patients NASH management
- that is a broader remit
Some of the numbers of patients with F stages are inconsistent with Table 2.
Plain language summary
Table 2 states that over 2% patients were of F stage unknown. Inconsistencies between text and
tables.
Background.
Lines 82-3. Please add a reference for the statement "The severity of liver fibrosis.......and
protective factors."
Cited reference 7 could be embellished with other recent SLRs in this space.
Methods:
Table 1 described study attrition of patients who had been diagnosed NASH by the contributing
physicians  documenting the final sample.  I looked at the  numbers excluded and calculated
attrition rates as  follows:   ALL (n=777 or 24.7%), PCPs  (n=78 or 35%), Gastroenterologists
(n=317 or 21%), Hepatologists (n=87 or 10.6%) and endocrinologists (n=295 or 48.4%), This
was not shown in the Table 1 or commented upon. I would suggest this is of note for physicians
who state "they manage at least 20 NASH patients per month". The study aims to describe non-
academic center management by specialty after all.
Study measures.  You state that data was collected regarding patient experiences with NASH
diagnosis and treatment.  Was this physician or patient basis. I missed this in the paper.
Results:
Patient demographics by ethnicity -
Line 166. You state between 61% and 69% of patients were currently employed.  Patients with
F4 Fibrosis stage in Table 2 were 40% employed. Severe NASH impacts work-life balance and
QOL. This should be highlighted.
There are inconsistencies between text and Figures 1 and 2. Also there are (I believe)
inconsistencies between Figure 1 and 2A.
Figure 1 & 2A.
Table 2 describes of the whole study group (n=2,366) there were 189 patients with F0 in the
study.  Figure 1 and 2A  describe  234 patients with F0. Please correct.
Despite having the same denominators per F stage.
Discussion.
Liver biopsy remains the standard for NASH diagnosis and F staging. This study acknowledges
the (unexpected) high proportion of patients having undergone a liver biopsy across these
participating physicians. And more could perhaps be made of this observation by revisiting these
centers or importantly by updating this (as the authors acknowledge) 6-7 year old data collected
in 2016 and 2017.  Citing research in other jurisdictions would validate this point, namely of
low use of liver biopsies.  It could also suggest the participating physicians in this study  are as
'expert' as those in US academic centers of course.  The eligibility of participating patients here
is not dissimilar to other Real World studies elsewhere outside USA.
Line 259-262. What is the reference supporting the sentence: "Despite the well
documented...........stage of fibrosis in this analysis."
Line 262-263. What is the reference to support the sentence: "It  is possible that there is....with
genotype offset."
Lines 283-288. Currently, in the absence of treatments indicated for the treatment of NASH,
pharmacological treatments prescribed by  clinicians/specialists worldwide  are prescribed to
control the underlying risk factors of NASH (i.e. T2D, obesity) and this study endorses these
observations. Citing other researchers work would be expected here.  Their conclusions were
almost identical.
Limitations.
The authors rightly acknowledge the age of the data in the study.  It would be optimal to repeat
this exercise to see the current state of affairs.  Or at a minimum look to see if 2016 vs 2017
were the same or exhibited trends of change?  Perhaps there are too many variables.
Discussion.
A number of the suggestions posed in the discussion suggest the participating physicians are
specialized experts and that the management is not dissimilar to 'academic centers'
Lines 259-263. What are the references supporting the statements spanning the text: "Despite
the well documented.......high-risk nutrients with genotype offset".. I do not understand this.
Please review this paper.
user
Title: Clinical Characteristics and Management of Patients with Nonalcoholic Steatohepatitis
in a Real-World Setting: Analysis of the Ipsos NASH Therapy Monitor Database
Version: 2 Date: 24 Jan 2023
Reviewer's report:
GENERAL COMMENTS.
This cross-sectional database study  in USA provides two "snapshots", in late 2016 and in late
2017, of patients assigned a clinical diagnosis of NASH, irrespective of diagnostic method.
It sought to assess the demographic and clinical characteristics of patients according to their
fibrosis stage and also to understand the diagnostic testing  and treatment regimes by fibrosis
stage, physician specialty and ethnicity in a real-world, but specifically not an academic US
medical center.
In reviewing any paper to assess its potential value to the medical literature, I look to see the
nature of any new findings ,  how it might compare to other evidence from other relevant studies,
any limitations and the potential impact of said new findings.
Essentially using this criteria I did not find much new which could influence clinical practice
that has not been voiced in other publications.  It did raise some questions which could merit
further exploration in future studies in order to address them. There was a lot of data, some not
utilized, and there were some inconsistencies in the paper. The cited references were very US
centric and  could and should have drawn upon other relevant publications from other countries,
potentially allowing the authors opportunities to compare their findings with others (who found
similar observations and offered similar 'ways forward' in general).  A few statements in the
paper required the addition of a reference.
SOME  SPECIFIC COMMENTS
Abstract
This study assesses   treatment regimes rather than management of patients NASH management
- that is a broader remit
Some of the numbers of patients with F stages are inconsistent with Table 2.
Plain language summary
Table 2 states that over 2% patients were of F stage unknown. Inconsistencies between text and
tables.
Background.
Lines 82-3. Please add a reference for the statement "The severity of liver fibrosis.......and
protective factors."
Cited reference 7 could be embellished with other recent SLRs in this space.
Methods:
Table 1 described study attrition of patients who had been diagnosed NASH by the contributing
physicians  documenting the final sample.  I looked at the  numbers excluded and calculated
attrition rates as  follows:   ALL (n=777 or 24.7%), PCPs  (n=78 or 35%), Gastroenterologists
(n=317 or 21%), Hepatologists (n=87 or 10.6%) and endocrinologists (n=295 or 48.4%), This
was not shown in the Table 1 or commented upon. I would suggest this is of note for physicians
who state "they manage at least 20 NASH patients per month". The study aims to describe non-
academic center management by specialty after all.
Study measures.  You state that data was collected regarding patient experiences with NASH
diagnosis and treatment.  Was this physician or patient basis. I missed this in the paper.
Results:
Patient demographics by ethnicity -
Line 166. You state between 61% and 69% of patients were currently employed.  Patients with
F4 Fibrosis stage in Table 2 were 40% employed. Severe NASH impacts work-life balance and
QOL. This should be highlighted.
There are inconsistencies between text and Figures 1 and 2. Also there are (I believe)
inconsistencies between Figure 1 and 2A.
Figure 1 & 2A.
Table 2 describes of the whole study group (n=2,366) there were 189 patients with F0 in the
study.  Figure 1 and 2A  describe  234 patients with F0. Please correct.
Despite having the same denominators per F stage.
Discussion.
Liver biopsy remains the standard for NASH diagnosis and F staging. This study acknowledges
the (unexpected) high proportion of patients having undergone a liver biopsy across these
participating physicians. And more could perhaps be made of this observation by revisiting these
centers or importantly by updating this (as the authors acknowledge) 6-7 year old data collected
in 2016 and 2017.  Citing research in other jurisdictions would validate this point, namely of
low use of liver biopsies.  It could also suggest the participating physicians in this study  are as
'expert' as those in US academic centers of course.  The eligibility of participating patients here
is not dissimilar to other Real World studies elsewhere outside USA.
Line 259-262. What is the reference supporting the sentence: "Despite the well
documented...........stage of fibrosis in this analysis."
Line 262-263. What is the reference to support the sentence: "It  is possible that there is....with
genotype offset."
Lines 283-288. Currently, in the absence of treatments indicated for the treatment of NASH,
pharmacological treatments prescribed by  clinicians/specialists worldwide  are prescribed to
control the underlying risk factors of NASH (i.e. T2D, obesity) and this study endorses these
observations. Citing other researchers work would be expected here.  Their conclusions were
almost identical.
Limitations.
The authors rightly acknowledge the age of the data in the study.  It would be optimal to repeat
this exercise to see the current state of affairs.  Or at a minimum look to see if 2016 vs 2017
were the same or exhibited trends of change?  Perhaps there are too many variables.
Discussion.
A number of the suggestions posed in the discussion suggest the participating physicians are
specialized experts and that the management is not dissimilar to 'academic centers'
Lines 259-263. What are the references supporting the statements spanning the text: "Despite
the well documented.......high-risk nutrients with genotype offset".. I do not understand this.
assistant