Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 06 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The background includes several references to lipid metabolism but doesn't delve deeply into
how the accumulation of small dense LDL (sdLDL) might contribute to the progression of
NAFLD to more severe conditions like NASH or cirrhosis. A brief mention of how sdLDL
could potentially accelerate liver damage or fibrosis progression could strengthen the rationale
for investigating EsdLDL-C in the context of NAFLD.
-The explanation about sdLDL’s atherogenicity is helpful, but it would be beneficial to expand
slightly on how this property might influence liver disease progression, in addition to its
cardiovascular effects. For example, does the increased permeability of sdLDL particles to the
arterial wall have a parallel effect on the liver, such as promoting inflammation or fibrosis?
-While the formula for calculating EsdLDL-C is provided, it might be helpful to explain why
triglycerides are involved in the formula. Since TG is a central component of lipid metabolism
and is often elevated in NAFLD, a brief explanation of the rationale behind using TG alongside
LDL-C would help readers understand the underlying relationship.
-The inclusion criteria are clear, but there is no mention of how the diagnosis of NAFLD was
made in the patients. It would be helpful to specify the diagnostic criteria used to ensure that the
population truly has NAFLD and not another condition that might confound the results, such as
alcoholic liver disease or viral hepatitis.
-Although the CAP score is described as a continuous variable that detects the severity of hepatic
steatosis, a brief explanation of the specific thresholds for diagnosing mild, moderate, or severe
steatosis would be beneficial. This would clarify for readers how the CAP value categorizes the
patients and ensures consistency in the classification of disease severity.
-While the study effectively demonstrates the predictive value of EsdLDL-C for Mod-Sev
steatosis, it could provide further explanation regarding why EsdLDL-C correlates with disease
severity. A more detailed mechanistic explanation of how elevated sdLDL might contribute to
the progression of hepatic steatosis (e.g., via inflammation or fibrosis) would help readers better
understand the clinical significance of EsdLDL-C as a marker for severity.
-The discussion mentions that both EsdLDL-C and DsdLDL-C are affected by TG levels, but
there is no detailed exploration of why this is the case. Since elevated TG is a key feature of
NAFLD and has an impact on lipid metabolism, further elaboration on the influence of TG on
sdLDL levels and its potential confounding role would be beneficial.
-The study mentions that EsdLDL-C outperforms other methods due to its cost-effectiveness, but
a deeper comparison with alternative markers (e.g., lipid profiles, liver enzymes) for predicting
NAFLD severity would strengthen the argument. How does EsdLDL-C compare to other
potential markers in terms of predictive accuracy or clinical utility?
Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 06 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The background includes several references to lipid metabolism but doesn't delve deeply into
how the accumulation of small dense LDL (sdLDL) might contribute to the progression of
NAFLD to more severe conditions like NASH or cirrhosis. A brief mention of how sdLDL
could potentially accelerate liver damage or fibrosis progression could strengthen the rationale
for investigating EsdLDL-C in the context of NAFLD.
-The explanation about sdLDL’s atherogenicity is helpful, but it would be beneficial to expand
slightly on how this property might influence liver disease progression, in addition to its
cardiovascular effects. For example, does the increased permeability of sdLDL particles to the
arterial wall have a parallel effect on the liver, such as promoting inflammation or fibrosis?
-While the formula for calculating EsdLDL-C is provided, it might be helpful to explain why
triglycerides are involved in the formula. Since TG is a central component of lipid metabolism
and is often elevated in NAFLD, a brief explanation of the rationale behind using TG alongside
LDL-C would help readers understand the underlying relationship.
-The inclusion criteria are clear, but there is no mention of how the diagnosis of NAFLD was
made in the patients. It would be helpful to specify the diagnostic criteria used to ensure that the
population truly has NAFLD and not another condition that might confound the results, such as
alcoholic liver disease or viral hepatitis.
-Although the CAP score is described as a continuous variable that detects the severity of hepatic
steatosis, a brief explanation of the specific thresholds for diagnosing mild, moderate, or severe
steatosis would be beneficial. This would clarify for readers how the CAP value categorizes the
patients and ensures consistency in the classification of disease severity.
-While the study effectively demonstrates the predictive value of EsdLDL-C for Mod-Sev
steatosis, it could provide further explanation regarding why EsdLDL-C correlates with disease
severity. A more detailed mechanistic explanation of how elevated sdLDL might contribute to
the progression of hepatic steatosis (e.g., via inflammation or fibrosis) would help readers better
understand the clinical significance of EsdLDL-C as a marker for severity.
-The discussion mentions that both EsdLDL-C and DsdLDL-C are affected by TG levels, but
there is no detailed exploration of why this is the case. Since elevated TG is a key feature of
NAFLD and has an impact on lipid metabolism, further elaboration on the influence of TG on
sdLDL levels and its potential confounding role would be beneficial.
-The study mentions that EsdLDL-C outperforms other methods due to its cost-effectiveness, but
a deeper comparison with alternative markers (e.g., lipid profiles, liver enzymes) for predicting
NAFLD severity would strengthen the argument. How does EsdLDL-C compare to other
potential markers in terms of predictive accuracy or clinical utility?
Please review this paper.
user
Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 06 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The background includes several references to lipid metabolism but doesn't delve deeply into
how the accumulation of small dense LDL (sdLDL) might contribute to the progression of
NAFLD to more severe conditions like NASH or cirrhosis. A brief mention of how sdLDL
could potentially accelerate liver damage or fibrosis progression could strengthen the rationale
for investigating EsdLDL-C in the context of NAFLD.
-The explanation about sdLDL’s atherogenicity is helpful, but it would be beneficial to expand
slightly on how this property might influence liver disease progression, in addition to its
cardiovascular effects. For example, does the increased permeability of sdLDL particles to the
arterial wall have a parallel effect on the liver, such as promoting inflammation or fibrosis?
-While the formula for calculating EsdLDL-C is provided, it might be helpful to explain why
triglycerides are involved in the formula. Since TG is a central component of lipid metabolism
and is often elevated in NAFLD, a brief explanation of the rationale behind using TG alongside
LDL-C would help readers understand the underlying relationship.
-The inclusion criteria are clear, but there is no mention of how the diagnosis of NAFLD was
made in the patients. It would be helpful to specify the diagnostic criteria used to ensure that the
population truly has NAFLD and not another condition that might confound the results, such as
alcoholic liver disease or viral hepatitis.
-Although the CAP score is described as a continuous variable that detects the severity of hepatic
steatosis, a brief explanation of the specific thresholds for diagnosing mild, moderate, or severe
steatosis would be beneficial. This would clarify for readers how the CAP value categorizes the
patients and ensures consistency in the classification of disease severity.
-While the study effectively demonstrates the predictive value of EsdLDL-C for Mod-Sev
steatosis, it could provide further explanation regarding why EsdLDL-C correlates with disease
severity. A more detailed mechanistic explanation of how elevated sdLDL might contribute to
the progression of hepatic steatosis (e.g., via inflammation or fibrosis) would help readers better
understand the clinical significance of EsdLDL-C as a marker for severity.
-The discussion mentions that both EsdLDL-C and DsdLDL-C are affected by TG levels, but
there is no detailed exploration of why this is the case. Since elevated TG is a key feature of
NAFLD and has an impact on lipid metabolism, further elaboration on the influence of TG on
sdLDL levels and its potential confounding role would be beneficial.
-The study mentions that EsdLDL-C outperforms other methods due to its cost-effectiveness, but
a deeper comparison with alternative markers (e.g., lipid profiles, liver enzymes) for predicting
NAFLD severity would strengthen the argument. How does EsdLDL-C compare to other
potential markers in terms of predictive accuracy or clinical utility?
assistant