Review for 10.1186/s12876-025-03903-1 (2025)

Title: Characteristics of serum bile acid profiles among individuals with metabolic dysfunction-
associated steatotic liver disease
Version: 0 Date: 02 Mar 2025
Reviewer:  Bryan Adrian Priego-Parra
Reviewer's report:
I appreciate the invitattion to review this manuscript, in which the authors aim to compare
serum bile acid profiles between individuals with MAFLD and healthy subjects. They found
differences in the profiles, and more importantly, they identified sex-related differences, which
likely reflect part of the sexual dimorphism observed in NAFLD/MAFLD/MASLD.
This is an interesting article. Below are my suggestions:
General comments:
1. In accordance with the latest medical and scientific writing guidelines, I recommend avoiding
the use of 'Sex/Gender,' 'Female/Women,' or 'Male/Men' as synonyms. Instead, I suggest
standardizing the terminology throughout the text, figures and tables by using only 'Sex,'
'Women,' and 'Men.'"
2. The notation for p-values should be lowercase ("p" instead of "P").
Abstract
Page 2
• Line 4: In the sentence “In this study, we delved into the alterations and delineation of
BA profiles within the cohort of individuals afflicted with MAFLD,” I suggest expressing the
objective more clearly. For example: “In this study, we aim to compare the serum BA profiles...”
• Line 7 (Methods): Consider starting directly with the study design and removing “We evaluated
the BA profiles of patients with MAFLD and healthy controls in this” (this information should
be stated in the objective).
• Line 15 (Results): Include the percentage of men and women in both the MAFLD and control
groups. For example: “A total of 215 (x% women) participants with MAFLD and 49 controls
(x% women) were included.”
• Line 16: Consider replacing “The serum BA profiles of patients differed significantly from
those of healthy individuals” with “MAFLD patients showed higher levels of serum total BA
(TBA), cholic acid (CA), chenodeoxycholic acid (CDCA), and ursodeoxycholic acid (UDCA)
(p < 0.05, p < 0.01) when compared to controls.”
Introduction
• Page 3, Line 3: I suggest rewording the beginning as follows: “Metabolic dysfunction-
associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver
disease (NAFLD), encompasses a broad spectrum of metabolic stress-related liver injuries,
predominantly characterized by fat storage, inflammation, and in some cases, leading to necrosis
of liver parenchymal cells.”
• Page 3, Line 9: In the sentence “Currently, the US Food and Drug Administration has granted
approval solely to Rezdiffra”, I recommend removing the brand name and instead stating
“resmetirom.”
• Page 3, Line 30: In “In this study, we employed the widely used ultra-high-performance liquid
chromatography-tandem mass spectrometry (UPLC-MS/MS) to quantitatively analyze serum
BA profiles in participants with MAFLD and explored their characteristics,” I suggest rewording
the general objective according to the research question. The phrase “we employed the widely
used ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/
MS)” should be included in the Methods section instead.
Methods
• Page 3, Line 38 (Study Design): How was the sample size estimated? If it was a non-
randomized convenience sample, I suggest stating this explicitly and acknowledging it as a
limitation.
• Page 4, Line 14: Although the MAFLD nomenclature does not exclude other liver diseases,
was screening performed for dual etiologies such as alcohol use or viral hepatitis? These factors
could impact bile acid metabolism. If such conditions were excluded, please state so. If not, I
suggest acknowledging this as a limitation.
• Page 5 (Statistical Analysis): Change “interquartile distance” to “interquartile range.”
Additionally, the results mention a Spearman correlation, but this is not described in the Methods
section. I suggest adding it.
Discussion
• Limitations: Add that the cross-sectional design prevents causal inferences. Also, mention
that the sample sizes of the MAFLD and control groups are different, which may affect the
interpretation of the analysis (215 vs. 49).
• I suggest updating the references, as 56% are over five years old. Consider including
PMID: 37759756, a recent meta-analysis that supports your findings. Additionally, in the “sex
differences” section, I recommend discussing some of the following articles: PMID: 39391907,
PMID: 38890029, PMID: 38901566, PMID: 38853100, PMID: 37854184.
Good work, and thank you for the invitation.