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: 1 Date: 15 Dec 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Yu et al. used data from
the 1999 and 2018 National Health and Nutrition Examination Survey (NHANES) for adult
Americans, to ensure a large, diverse, and well-characterized population with reliable follow-
up data. This research aims to explore the associations between ALI and liver fibrosis risk,
along with its relationship to all-cause, cardiovascular disease (CVD), and cancer mortality in
NAFLD patients. The study included multiple statistical approaches (e.g., logistic regression,
Cox proportional hazards models, and restricted cubic splines) to ensure a rigorous exploration
of associations.
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. Abbreviations must be fully written at their first appearance
In Title:
3. The authors may consider indicating the locality at which the National Health and Nutrition
Examination Survey (NHANES) was performed.
4. While the Advanced Lung Cancer Inflammation Index (ALI) is central to the study, it is not
mentioned explicitly in the title.
5. I suggest "The Role of the Advanced Lung Cancer Inflammation Index (ALI) in the Risk of
Liver Fibrosis and Mortality Among US Adult NAFLD Patients: A Cross-Sectional Study of
NHANES 1999–2018" as a title.
6. “Non-alcoholic fatty liver disease (NAFLD)” is a broad expression that encompasses a
variety of conditions, including “non-alcoholic fatty liver (NAFLD, steatosis)”, intrahepatic
lipid accumulation without any secondary cause of liver fat accumulation such as heavy alcohol
consumption, of at least 5% of the liver weight that causes liver dysfunction and inflammation,
and advance to “non-alcoholic steatohepatitis (NASH)”, which is distinguished by liver fibrosis,
which advances to cirrhosis, and hepatocellular carcinoma in about 30–40% of cases. Thus, the
disease spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis.
Which of them is the scope of your study to be identified in the title?
7. Non-alcoholic fatty liver disease (NAFLD) nomenclature had several limitations, the name
chosen to replace NAFLD is metabolic dysfunction-associated Steatotic liver disease (MASLD)
(Ref: doi.org/10.1186/s12876-024-03310-y).
In Abstract section
8. In method: please use “Using data from the National Health and Nutrition Examination Survey
(NHANES) database spanning from 1999 to 2018, a cross-sectional study included 5,388 adult
US participants was performed to assess the relationship …….”.
9. It would help if you described the aim of your statistical analysis used throughout the study.
10. Nothing was mentioned about the participant’s age, sex, ethnicity, etc.
11. The type of study: a population-based study.
In the Introduction section:
12. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are some laboratory components.”.
In the Methods section:
13. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
14. Please provide the participants' sociodemographic data.
15. How MAFLD was diagnosed?
16. The methodology lacks detailed justification for the selection of ALI thresholds and the
stratification process
17. What was the source of the covariate data?
18. Justify the thresholds used for step count and intensity categories by referencing prior
literature or explaining their clinical relevance.
19. Expand on the exclusion and inclusion criteria.
In the Results section:
20. In Tables: You can title the statistical test column as “Test of significance” and use U= for
the Mann–Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc.
21. Subgroup analyses must be performed to evaluate the effect of studied variables on mortality
rate and their stability in different populations. Subgroup analyses based on differences in
diagnostic components were performed to elaborate correlations. The results were presented in
forest plots using odds ratios (ORs) and 95% confidence intervals (CIs).
22. Log2 logarithmic transformation shall be analyzed.
23. Provide a clearer interpretation of the non-linear relationships identified through restricted
cubic splines. For instance, explain the clinical significance of the inflection points (e.g., ALI
thresholds of 38 and 131.78).
24. The marital status category should be categorized into cohabitation (married/living with a
partner) and solitude (widowed/divorced/separated/unmarried).”
In the Discussion section:
25. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion between
what should be written in the introduction section and the discussion section. Please reconstruct
the discussion section.
26. Discuss the potential biological mechanisms linking ALI to liver fibrosis and mortality,
drawing on studies of systemic inflammation, albumin function, and BMI.
27. The bias associated with using a self-reported outcome variable was not mentioned by the
authors.
28. Compare the predictive utility of ALI with other biomarkers (e.g., NLR, Fibrosis-4 Index)
to emphasize its clinical relevance.
29. Discuss the novelty of your study. Highlight how this study advances understanding
compared to prior work on inflammatory and nutritional biomarkers in MAFLD.
30. Provide the limitations to address the cross-sectional design and its inability to establish
causality.
31. Propose actionable steps, such as incorporating ALI into NAFLD management guidelines
or routine clinical assessments.
32. Discuss future studies concerning the associations between ALI and liver fibrosis risk with
mortality among adult US individuals with MASLD.
33. Discuss the practical implications of your study.
In the conclusion section:
34. The conclusion should restate your main points and provide closure.
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: 1 Date: 15 Dec 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Yu et al. used data from
the 1999 and 2018 National Health and Nutrition Examination Survey (NHANES) for adult
Americans, to ensure a large, diverse, and well-characterized population with reliable follow-
up data. This research aims to explore the associations between ALI and liver fibrosis risk,
along with its relationship to all-cause, cardiovascular disease (CVD), and cancer mortality in
NAFLD patients. The study included multiple statistical approaches (e.g., logistic regression,
Cox proportional hazards models, and restricted cubic splines) to ensure a rigorous exploration
of associations.
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. Abbreviations must be fully written at their first appearance
In Title:
3. The authors may consider indicating the locality at which the National Health and Nutrition
Examination Survey (NHANES) was performed.
4. While the Advanced Lung Cancer Inflammation Index (ALI) is central to the study, it is not
mentioned explicitly in the title.
5. I suggest "The Role of the Advanced Lung Cancer Inflammation Index (ALI) in the Risk of
Liver Fibrosis and Mortality Among US Adult NAFLD Patients: A Cross-Sectional Study of
NHANES 1999–2018" as a title.
6. “Non-alcoholic fatty liver disease (NAFLD)” is a broad expression that encompasses a
variety of conditions, including “non-alcoholic fatty liver (NAFLD, steatosis)”, intrahepatic
lipid accumulation without any secondary cause of liver fat accumulation such as heavy alcohol
consumption, of at least 5% of the liver weight that causes liver dysfunction and inflammation,
and advance to “non-alcoholic steatohepatitis (NASH)”, which is distinguished by liver fibrosis,
which advances to cirrhosis, and hepatocellular carcinoma in about 30–40% of cases. Thus, the
disease spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis.
Which of them is the scope of your study to be identified in the title?
7. Non-alcoholic fatty liver disease (NAFLD) nomenclature had several limitations, the name
chosen to replace NAFLD is metabolic dysfunction-associated Steatotic liver disease (MASLD)
(Ref: doi.org/10.1186/s12876-024-03310-y).
In Abstract section
8. In method: please use “Using data from the National Health and Nutrition Examination Survey
(NHANES) database spanning from 1999 to 2018, a cross-sectional study included 5,388 adult
US participants was performed to assess the relationship …….”.
9. It would help if you described the aim of your statistical analysis used throughout the study.
10. Nothing was mentioned about the participant’s age, sex, ethnicity, etc.
11. The type of study: a population-based study.
In the Introduction section:
12. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are some laboratory components.”.
In the Methods section:
13. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
14. Please provide the participants' sociodemographic data.
15. How MAFLD was diagnosed?
16. The methodology lacks detailed justification for the selection of ALI thresholds and the
stratification process
17. What was the source of the covariate data?
18. Justify the thresholds used for step count and intensity categories by referencing prior
literature or explaining their clinical relevance.
19. Expand on the exclusion and inclusion criteria.
In the Results section:
20. In Tables: You can title the statistical test column as “Test of significance” and use U= for
the Mann–Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc.
21. Subgroup analyses must be performed to evaluate the effect of studied variables on mortality
rate and their stability in different populations. Subgroup analyses based on differences in
diagnostic components were performed to elaborate correlations. The results were presented in
forest plots using odds ratios (ORs) and 95% confidence intervals (CIs).
22. Log2 logarithmic transformation shall be analyzed.
23. Provide a clearer interpretation of the non-linear relationships identified through restricted
cubic splines. For instance, explain the clinical significance of the inflection points (e.g., ALI
thresholds of 38 and 131.78).
24. The marital status category should be categorized into cohabitation (married/living with a
partner) and solitude (widowed/divorced/separated/unmarried).”
In the Discussion section:
25. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion between
what should be written in the introduction section and the discussion section. Please reconstruct
the discussion section.
26. Discuss the potential biological mechanisms linking ALI to liver fibrosis and mortality,
drawing on studies of systemic inflammation, albumin function, and BMI.
27. The bias associated with using a self-reported outcome variable was not mentioned by the
authors.
28. Compare the predictive utility of ALI with other biomarkers (e.g., NLR, Fibrosis-4 Index)
to emphasize its clinical relevance.
29. Discuss the novelty of your study. Highlight how this study advances understanding
compared to prior work on inflammatory and nutritional biomarkers in MAFLD.
30. Provide the limitations to address the cross-sectional design and its inability to establish
causality.
31. Propose actionable steps, such as incorporating ALI into NAFLD management guidelines
or routine clinical assessments.
32. Discuss future studies concerning the associations between ALI and liver fibrosis risk with
mortality among adult US individuals with MASLD.
33. Discuss the practical implications of your study.
In the conclusion section:
34. The conclusion should restate your main points and provide closure.
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: 1 Date: 15 Dec 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Yu et al. used data from
the 1999 and 2018 National Health and Nutrition Examination Survey (NHANES) for adult
Americans, to ensure a large, diverse, and well-characterized population with reliable follow-
up data. This research aims to explore the associations between ALI and liver fibrosis risk,
along with its relationship to all-cause, cardiovascular disease (CVD), and cancer mortality in
NAFLD patients. The study included multiple statistical approaches (e.g., logistic regression,
Cox proportional hazards models, and restricted cubic splines) to ensure a rigorous exploration
of associations.
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. Abbreviations must be fully written at their first appearance
In Title:
3. The authors may consider indicating the locality at which the National Health and Nutrition
Examination Survey (NHANES) was performed.
4. While the Advanced Lung Cancer Inflammation Index (ALI) is central to the study, it is not
mentioned explicitly in the title.
5. I suggest "The Role of the Advanced Lung Cancer Inflammation Index (ALI) in the Risk of
Liver Fibrosis and Mortality Among US Adult NAFLD Patients: A Cross-Sectional Study of
NHANES 1999–2018" as a title.
6. “Non-alcoholic fatty liver disease (NAFLD)” is a broad expression that encompasses a
variety of conditions, including “non-alcoholic fatty liver (NAFLD, steatosis)”, intrahepatic
lipid accumulation without any secondary cause of liver fat accumulation such as heavy alcohol
consumption, of at least 5% of the liver weight that causes liver dysfunction and inflammation,
and advance to “non-alcoholic steatohepatitis (NASH)”, which is distinguished by liver fibrosis,
which advances to cirrhosis, and hepatocellular carcinoma in about 30–40% of cases. Thus, the
disease spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis.
Which of them is the scope of your study to be identified in the title?
7. Non-alcoholic fatty liver disease (NAFLD) nomenclature had several limitations, the name
chosen to replace NAFLD is metabolic dysfunction-associated Steatotic liver disease (MASLD)
(Ref: doi.org/10.1186/s12876-024-03310-y).
In Abstract section
8. In method: please use “Using data from the National Health and Nutrition Examination Survey
(NHANES) database spanning from 1999 to 2018, a cross-sectional study included 5,388 adult
US participants was performed to assess the relationship …….”.
9. It would help if you described the aim of your statistical analysis used throughout the study.
10. Nothing was mentioned about the participant’s age, sex, ethnicity, etc.
11. The type of study: a population-based study.
In the Introduction section:
12. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are some laboratory components.”.
In the Methods section:
13. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
14. Please provide the participants' sociodemographic data.
15. How MAFLD was diagnosed?
16. The methodology lacks detailed justification for the selection of ALI thresholds and the
stratification process
17. What was the source of the covariate data?
18. Justify the thresholds used for step count and intensity categories by referencing prior
literature or explaining their clinical relevance.
19. Expand on the exclusion and inclusion criteria.
In the Results section:
20. In Tables: You can title the statistical test column as “Test of significance” and use U= for
the Mann–Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc.
21. Subgroup analyses must be performed to evaluate the effect of studied variables on mortality
rate and their stability in different populations. Subgroup analyses based on differences in
diagnostic components were performed to elaborate correlations. The results were presented in
forest plots using odds ratios (ORs) and 95% confidence intervals (CIs).
22. Log2 logarithmic transformation shall be analyzed.
23. Provide a clearer interpretation of the non-linear relationships identified through restricted
cubic splines. For instance, explain the clinical significance of the inflection points (e.g., ALI
thresholds of 38 and 131.78).
24. The marital status category should be categorized into cohabitation (married/living with a
partner) and solitude (widowed/divorced/separated/unmarried).”
In the Discussion section:
25. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion between
what should be written in the introduction section and the discussion section. Please reconstruct
the discussion section.
26. Discuss the potential biological mechanisms linking ALI to liver fibrosis and mortality,
drawing on studies of systemic inflammation, albumin function, and BMI.
27. The bias associated with using a self-reported outcome variable was not mentioned by the
authors.
28. Compare the predictive utility of ALI with other biomarkers (e.g., NLR, Fibrosis-4 Index)
to emphasize its clinical relevance.
29. Discuss the novelty of your study. Highlight how this study advances understanding
compared to prior work on inflammatory and nutritional biomarkers in MAFLD.
30. Provide the limitations to address the cross-sectional design and its inability to establish
causality.
31. Propose actionable steps, such as incorporating ALI into NAFLD management guidelines
or routine clinical assessments.
32. Discuss future studies concerning the associations between ALI and liver fibrosis risk with
mortality among adult US individuals with MASLD.
33. Discuss the practical implications of your study.
In the conclusion section:
34. The conclusion should restate your main points and provide closure.
assistant