Title: The Role of the Advanced Lung Cancer Inflammation Index (ALI) in the Risk of
Liver Fibrosis and Mortality Among US Adult MAFLD Patients: A Cross-Sectional Study of
NHANES 1999–2018
Version: 2 Date: 02 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the ALI is well-justified in terms of its role as an inflammatory and nutritional marker,
the manuscript would benefit from a deeper discussion of the biological mechanisms linking
ALI to liver fibrosis in MAFLD. The authors could elaborate on how BMI, albumin, and NLR
are related to liver inflammation and fibrosis progression. The current explanation lacks clarity
on how these components interact in the liver microenvironment.
-It would also be helpful to compare ALI to other known inflammatory markers in MAFLD (e.g.,
C-reactive protein (CRP), NLR) and explain why ALI is specifically chosen. While the index
has been used in various cancer-related and inflammatory conditions, MAFLD-specific studies
are limited, and further justification would strengthen the rationale for its use in this population.
-The manuscript uses the USFLI index to define fatty liver, but it would be useful to provide more
information on the sensitivity and specificity of the USFLI compared to imaging or histological
assessment of liver steatosis. While the use of USFLI is appropriate for large population studies,
its limitations in diagnosing MAFLD could impact the validity of the findings. A brief discussion
of how the USFLI compares to other diagnostic criteria for fatty liver disease would strengthen
the study's diagnostic accuracy argument.
-While the authors adjust for many important covariates (e.g., age, sex, BMI, smoking, alcohol
consumption), the manuscript could further clarify how the covariates were chosen. Were these
based on prior literature, or were they identified through exploratory data analysis? Providing a
more explicit rationale for the selection of specific covariates, particularly lifestyle factors like
physical inactivity or dietary intake, would enhance transparency and ensure that the analysis
adequately addresses potential confounding.
-The stratified analyses by central obesity, prediabetes, and alcohol consumption provide
important insights into how these factors influence the relationship between ALI and health
outcomes. However, the P-values for interactions (e.g., alcohol consumption and low HDL-
cholesterol) are reported as significant, but the actual interaction effects are not sufficiently
detailed. Providing a more thorough interpretation of these interactions, including the magnitude
of effect and clinical relevance, would enrich the discussion.
Title: The Role of the Advanced Lung Cancer Inflammation Index (ALI) in the Risk of
Liver Fibrosis and Mortality Among US Adult MAFLD Patients: A Cross-Sectional Study of
NHANES 1999–2018
Version: 2 Date: 02 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the ALI is well-justified in terms of its role as an inflammatory and nutritional marker,
the manuscript would benefit from a deeper discussion of the biological mechanisms linking
ALI to liver fibrosis in MAFLD. The authors could elaborate on how BMI, albumin, and NLR
are related to liver inflammation and fibrosis progression. The current explanation lacks clarity
on how these components interact in the liver microenvironment.
-It would also be helpful to compare ALI to other known inflammatory markers in MAFLD (e.g.,
C-reactive protein (CRP), NLR) and explain why ALI is specifically chosen. While the index
has been used in various cancer-related and inflammatory conditions, MAFLD-specific studies
are limited, and further justification would strengthen the rationale for its use in this population.
-The manuscript uses the USFLI index to define fatty liver, but it would be useful to provide more
information on the sensitivity and specificity of the USFLI compared to imaging or histological
assessment of liver steatosis. While the use of USFLI is appropriate for large population studies,
its limitations in diagnosing MAFLD could impact the validity of the findings. A brief discussion
of how the USFLI compares to other diagnostic criteria for fatty liver disease would strengthen
the study's diagnostic accuracy argument.
-While the authors adjust for many important covariates (e.g., age, sex, BMI, smoking, alcohol
consumption), the manuscript could further clarify how the covariates were chosen. Were these
based on prior literature, or were they identified through exploratory data analysis? Providing a
more explicit rationale for the selection of specific covariates, particularly lifestyle factors like
physical inactivity or dietary intake, would enhance transparency and ensure that the analysis
adequately addresses potential confounding.
-The stratified analyses by central obesity, prediabetes, and alcohol consumption provide
important insights into how these factors influence the relationship between ALI and health
outcomes. However, the P-values for interactions (e.g., alcohol consumption and low HDL-
cholesterol) are reported as significant, but the actual interaction effects are not sufficiently
detailed. Providing a more thorough interpretation of these interactions, including the magnitude
of effect and clinical relevance, would enrich the discussion.
Please review this paper.
user
Title: The Role of the Advanced Lung Cancer Inflammation Index (ALI) in the Risk of
Liver Fibrosis and Mortality Among US Adult MAFLD Patients: A Cross-Sectional Study of
NHANES 1999–2018
Version: 2 Date: 02 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the ALI is well-justified in terms of its role as an inflammatory and nutritional marker,
the manuscript would benefit from a deeper discussion of the biological mechanisms linking
ALI to liver fibrosis in MAFLD. The authors could elaborate on how BMI, albumin, and NLR
are related to liver inflammation and fibrosis progression. The current explanation lacks clarity
on how these components interact in the liver microenvironment.
-It would also be helpful to compare ALI to other known inflammatory markers in MAFLD (e.g.,
C-reactive protein (CRP), NLR) and explain why ALI is specifically chosen. While the index
has been used in various cancer-related and inflammatory conditions, MAFLD-specific studies
are limited, and further justification would strengthen the rationale for its use in this population.
-The manuscript uses the USFLI index to define fatty liver, but it would be useful to provide more
information on the sensitivity and specificity of the USFLI compared to imaging or histological
assessment of liver steatosis. While the use of USFLI is appropriate for large population studies,
its limitations in diagnosing MAFLD could impact the validity of the findings. A brief discussion
of how the USFLI compares to other diagnostic criteria for fatty liver disease would strengthen
the study's diagnostic accuracy argument.
-While the authors adjust for many important covariates (e.g., age, sex, BMI, smoking, alcohol
consumption), the manuscript could further clarify how the covariates were chosen. Were these
based on prior literature, or were they identified through exploratory data analysis? Providing a
more explicit rationale for the selection of specific covariates, particularly lifestyle factors like
physical inactivity or dietary intake, would enhance transparency and ensure that the analysis
adequately addresses potential confounding.
-The stratified analyses by central obesity, prediabetes, and alcohol consumption provide
important insights into how these factors influence the relationship between ALI and health
outcomes. However, the P-values for interactions (e.g., alcohol consumption and low HDL-
cholesterol) are reported as significant, but the actual interaction effects are not sufficiently
detailed. Providing a more thorough interpretation of these interactions, including the magnitude
of effect and clinical relevance, would enrich the discussion.
assistant