Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the
ClinicalTrials.gov Database
Version: 2 Date: 23 Jan 2025
Reviewer:  Joost Boeckmans
Reviewer's report:
Hui Du and colleagues provide an overview of clinical trials in MASLD registered on
ClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain
concepts could add innovative aspects, in which I hope my input can be useful:
Major
- Introduction: in my opinion, the introduction would benefit from discussing the potential drug
targets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on
prevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two-
hit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper.
- The authors describe hepatic fat content as a frequent endpoint. What about the technique to
quantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid
reduction? Same for histology, are there already some using AI?
- Based on the search, what are the advantages of current ‘most popular’ drugs under
development over the failed compounds? Eg. Elafibranor.
- What about personalized treatment developments? Eg. Regarding PNPLA3? When did these
kinds of approaches emerge?
All in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more
detail, since this informs about new developments
Minor
- Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette
JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA.
The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis.
Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0.
Epub 2022 Jul 5. PMID: 35798021.
- Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create
some uniformity.
- Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar
- Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through
mechanisms such as metabolic and energy balance”; would be informative to add a percentage
to this number. How did the targets change throughout the time?
- Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple
concepts (cfr methods section).
- Was gender (vs sex) adequately used?
- This quite recent article reported on the same topic: PMID:38327733. What is the added value
of this paper?
Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the
ClinicalTrials.gov Database
Version: 2 Date: 23 Jan 2025
Reviewer:  Joost Boeckmans
Reviewer's report:
Hui Du and colleagues provide an overview of clinical trials in MASLD registered on
ClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain
concepts could add innovative aspects, in which I hope my input can be useful:
Major
- Introduction: in my opinion, the introduction would benefit from discussing the potential drug
targets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on
prevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two-
hit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper.
- The authors describe hepatic fat content as a frequent endpoint. What about the technique to
quantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid
reduction? Same for histology, are there already some using AI?
- Based on the search, what are the advantages of current ‘most popular’ drugs under
development over the failed compounds? Eg. Elafibranor.
- What about personalized treatment developments? Eg. Regarding PNPLA3? When did these
kinds of approaches emerge?
All in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more
detail, since this informs about new developments
Minor
- Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette
JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA.
The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis.
Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0.
Epub 2022 Jul 5. PMID: 35798021.
- Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create
some uniformity.
- Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar
- Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through
mechanisms such as metabolic and energy balance”; would be informative to add a percentage
to this number. How did the targets change throughout the time?
- Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple
concepts (cfr methods section).
- Was gender (vs sex) adequately used?
- This quite recent article reported on the same topic: PMID:38327733. What is the added value
of this paper?
Please review this paper.
user
Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the
ClinicalTrials.gov Database
Version: 2 Date: 23 Jan 2025
Reviewer:  Joost Boeckmans
Reviewer's report:
Hui Du and colleagues provide an overview of clinical trials in MASLD registered on
ClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain
concepts could add innovative aspects, in which I hope my input can be useful:
Major
- Introduction: in my opinion, the introduction would benefit from discussing the potential drug
targets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on
prevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two-
hit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper.
- The authors describe hepatic fat content as a frequent endpoint. What about the technique to
quantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid
reduction? Same for histology, are there already some using AI?
- Based on the search, what are the advantages of current ‘most popular’ drugs under
development over the failed compounds? Eg. Elafibranor.
- What about personalized treatment developments? Eg. Regarding PNPLA3? When did these
kinds of approaches emerge?
All in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more
detail, since this informs about new developments
Minor
- Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette
JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA.
The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis.
Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0.
Epub 2022 Jul 5. PMID: 35798021.
- Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create
some uniformity.
- Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar
- Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through
mechanisms such as metabolic and energy balance”; would be informative to add a percentage
to this number. How did the targets change throughout the time?
- Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple
concepts (cfr methods section).
- Was gender (vs sex) adequately used?
- This quite recent article reported on the same topic: PMID:38327733. What is the added value
of this paper?
assistant