Title: Fetuin-A: A Relevant Novel Serum Biomarker for Non-Invasive Diagnosis of Metabolic
Dysfunction-Associated Steatotic Liver Disease (MASLD): A Retrospective Case-control Study
Version: 2 Date: 26 May 2024
Reviewer's report:
The authors present a n interesting article regarding the continuos struggle regarding non-
invasive biomarkers on MASLD. The article, though interesting, should be substantially
improved to reach publication status. Below are some of my major suggestions.
1. Fetuin-A is the major point of this article and should be present on full title and not only in
running title.
2. In background section, MASLD should replace NAFLD (ref: DOI:10.1097/
HEP.0000000000000520)
3. Also in background, the authors should add CAP as a non-invasive biomarker for the presence
of liver steatosis (ref: doi:10.1007/s00261-024-04347-z; doi:10.1002/dmrr.3787), even though
liver biopsy is still the gold standard method
4. In study design and settings the line "This investigation is planned to be conducted between
December 2021 and December 2022" should be at a past tense
5. Inclusion and exclusion criteria should be better explained: U/S does not show liver function,
unless the authors mean that no steatosis was found; the part regarding cirrhotic patient should
be narrowed down to just saying that patients with liver cirrhosis were not exluded; "minor
patients 'below 18Y' "should be replaced with patients under 18 years of age; chronic heavy
alcohol drinkers with patients with an alcohol intake of more than.... . Overall, the whole part
should be written in a more professional way
6. In the same part, metformin is not a treatment for MASLD; no liver assocations recommend
it due to lack of large scale studies. If patients under metformin were ecluded this should be
explained. Likewise, no GLP-1 or SGLT2 drugs are seen in this list. Why is that? Especially,
regarding GLP1 drugs much data exist (ref: doi:10.1056/NEJMoa2028395)
7. In 'clinical and biochemical characterization' part, why was only NFS score used? At least,
APRI and FIB-4 should also be included
8. Instead of using f0-f4 for transient elastography results, the authors are advised to use the
new EASL cutoffs as how or low risk for advanced liver disease patients (ref:   doi: 10.1016/
j.jhep.2021.05.025)
9. In discussion section, relevant article regarding non-invasive scores in patients with MASLD
should be added (ref: doi:10.1007/s00109-024-02448-2; doi:10.1097/HEP.0000000000000842;
doi:10.2174/1570162X17666190809153245)
10. Also in discussion section, lines 276-319 take too much space. Each one
of the authors' findings should not exceed 5 lines. giving more space for a
brief explanation of MASLD pathogenesis and give more space to fetuin-a in that
process (ref: doi:10.3390/cells11162511; doi:10.1080/1744666X.2023.2294046; doi:10.3390/
metabo12070625; doi:10.1007/s10787-021-00837-4 among others)
Title: Fetuin-A: A Relevant Novel Serum Biomarker for Non-Invasive Diagnosis of Metabolic
Dysfunction-Associated Steatotic Liver Disease (MASLD): A Retrospective Case-control Study
Version: 2 Date: 26 May 2024
Reviewer's report:
The authors present a n interesting article regarding the continuos struggle regarding non-
invasive biomarkers on MASLD. The article, though interesting, should be substantially
improved to reach publication status. Below are some of my major suggestions.
1. Fetuin-A is the major point of this article and should be present on full title and not only in
running title.
2. In background section, MASLD should replace NAFLD (ref: DOI:10.1097/
HEP.0000000000000520)
3. Also in background, the authors should add CAP as a non-invasive biomarker for the presence
of liver steatosis (ref: doi:10.1007/s00261-024-04347-z; doi:10.1002/dmrr.3787), even though
liver biopsy is still the gold standard method
4. In study design and settings the line "This investigation is planned to be conducted between
December 2021 and December 2022" should be at a past tense
5. Inclusion and exclusion criteria should be better explained: U/S does not show liver function,
unless the authors mean that no steatosis was found; the part regarding cirrhotic patient should
be narrowed down to just saying that patients with liver cirrhosis were not exluded; "minor
patients 'below 18Y' "should be replaced with patients under 18 years of age; chronic heavy
alcohol drinkers with patients with an alcohol intake of more than.... . Overall, the whole part
should be written in a more professional way
6. In the same part, metformin is not a treatment for MASLD; no liver assocations recommend
it due to lack of large scale studies. If patients under metformin were ecluded this should be
explained. Likewise, no GLP-1 or SGLT2 drugs are seen in this list. Why is that? Especially,
regarding GLP1 drugs much data exist (ref: doi:10.1056/NEJMoa2028395)
7. In 'clinical and biochemical characterization' part, why was only NFS score used? At least,
APRI and FIB-4 should also be included
8. Instead of using f0-f4 for transient elastography results, the authors are advised to use the
new EASL cutoffs as how or low risk for advanced liver disease patients (ref:   doi: 10.1016/
j.jhep.2021.05.025)
9. In discussion section, relevant article regarding non-invasive scores in patients with MASLD
should be added (ref: doi:10.1007/s00109-024-02448-2; doi:10.1097/HEP.0000000000000842;
doi:10.2174/1570162X17666190809153245)
10. Also in discussion section, lines 276-319 take too much space. Each one
of the authors' findings should not exceed 5 lines. giving more space for a
brief explanation of MASLD pathogenesis and give more space to fetuin-a in that
process (ref: doi:10.3390/cells11162511; doi:10.1080/1744666X.2023.2294046; doi:10.3390/
metabo12070625; doi:10.1007/s10787-021-00837-4 among others)
Please review this paper.
user
Title: Fetuin-A: A Relevant Novel Serum Biomarker for Non-Invasive Diagnosis of Metabolic
Dysfunction-Associated Steatotic Liver Disease (MASLD): A Retrospective Case-control Study
Version: 2 Date: 26 May 2024
Reviewer's report:
The authors present a n interesting article regarding the continuos struggle regarding non-
invasive biomarkers on MASLD. The article, though interesting, should be substantially
improved to reach publication status. Below are some of my major suggestions.
1. Fetuin-A is the major point of this article and should be present on full title and not only in
running title.
2. In background section, MASLD should replace NAFLD (ref: DOI:10.1097/
HEP.0000000000000520)
3. Also in background, the authors should add CAP as a non-invasive biomarker for the presence
of liver steatosis (ref: doi:10.1007/s00261-024-04347-z; doi:10.1002/dmrr.3787), even though
liver biopsy is still the gold standard method
4. In study design and settings the line "This investigation is planned to be conducted between
December 2021 and December 2022" should be at a past tense
5. Inclusion and exclusion criteria should be better explained: U/S does not show liver function,
unless the authors mean that no steatosis was found; the part regarding cirrhotic patient should
be narrowed down to just saying that patients with liver cirrhosis were not exluded; "minor
patients 'below 18Y' "should be replaced with patients under 18 years of age; chronic heavy
alcohol drinkers with patients with an alcohol intake of more than.... . Overall, the whole part
should be written in a more professional way
6. In the same part, metformin is not a treatment for MASLD; no liver assocations recommend
it due to lack of large scale studies. If patients under metformin were ecluded this should be
explained. Likewise, no GLP-1 or SGLT2 drugs are seen in this list. Why is that? Especially,
regarding GLP1 drugs much data exist (ref: doi:10.1056/NEJMoa2028395)
7. In 'clinical and biochemical characterization' part, why was only NFS score used? At least,
APRI and FIB-4 should also be included
8. Instead of using f0-f4 for transient elastography results, the authors are advised to use the
new EASL cutoffs as how or low risk for advanced liver disease patients (ref:   doi: 10.1016/
j.jhep.2021.05.025)
9. In discussion section, relevant article regarding non-invasive scores in patients with MASLD
should be added (ref: doi:10.1007/s00109-024-02448-2; doi:10.1097/HEP.0000000000000842;
doi:10.2174/1570162X17666190809153245)
10. Also in discussion section, lines 276-319 take too much space. Each one
of the authors' findings should not exceed 5 lines. giving more space for a
brief explanation of MASLD pathogenesis and give more space to fetuin-a in that
process (ref: doi:10.3390/cells11162511; doi:10.1080/1744666X.2023.2294046; doi:10.3390/
metabo12070625; doi:10.1007/s10787-021-00837-4 among others)
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