Review for 10.1186/s12876-024-03544-w (2025)

Title: Advanced Lung Cancer Inflammation Index  A Key Predictor of Hepatic Steatosis and
Fibrosis Severity
Version: 2 Date: 07 Oct 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, LIU and WANG used data from
the 2017–2020 National Health and Nutrition Examination Survey (NHANES) for Americans,
this research examines the relationship between the Advanced Lung Cancer Inflammation Index
(ALI) and Controlled Attenuation Parameter (CAP) and Liver Stiffness Measurement (LSM),
aiming to early detection and recognition indicators of hepatic steatosis and hepatic fibrosis.
Lung cancer is one of the most commonly diagnosed cancers and the leading cause of mortality
worldwide, accounting for approximately 18% of all cancer deaths.  Despite major advances in
diagnostic strategies and effective new treatment modalities (such as immunotherapy), the 5#
year survival rate of lung cancer is only 10–20%*. Recently, rising evidences have indicated that
numerous nutrition/inflammation#related parameters can be exploited as excellent prognostic
indicators in lung cancer. It has been demonstrated that the progression and prognosis of patients
with lung cancer are significantly influenced by markers of the systemic inflammatory response,
such as the neutrophil-to-lymphocyte ratio (NLR) 8, platelet-to-lymphocyte ratio (PLR) 6, and
plasma C-reactive protein (CRP) levels**. Several researchers have reported on the predictive
importance of the advanced lung cancer inflammation index (ALI), which is determined by
multiplying the body mass index (BMI) by serum albumin/NLR. The results indicate that low
ALI is linked to a poor prognosis in lung cancer***.
(*: doi.org/10.3322/caac.21660, ** doi.org/10.1177/1758835920942378, ***: doi.org/10.1016/
j.cllc.2015.03.005).
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 the first appearance (FMPIR, BMI, DM, HTN, HL,
and ….etc.)
In Title:
3. The authors should consider indicating that the study is an insight from NHANES and
the locality at which the National Health and Nutrition Examination Survey (NHANES) was
performed (Adult Americans).
4. Metabolic dysfunction-associated steatotic liver disease (MASLD) formally known as Non-
alcoholic fatty liver disease (NAFLD) is a broad expression that encompasses a variety of
conditions, including “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 “liver cirrhosis”, and
“hepatocellular carcinoma” in about 30–40% of cases. Thus, the disease spectrum of MASLD
includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis. Which of them is the scope of
your study to be identified in the title?
In Abstract section
5. The background subsection:
-  Should be the shortest part of the abstract. It should very briefly outline the following
information: What is already known about the subject, related to the paper in question. What is
not known about the subject and hence what the study intended to examine (or what the paper
seeks to present). Please reconstruct it properly.
6.  What is the type of study: a population-based study?
7. In method subsection:
- please use “Using data from the National Health and Nutrition Examination Survey (NHANES)
database spanning from 2017 to 2020, a cross-sectional study included ***** participants was
performed to assess the relationship …….”.
- It would help if you described the aim of your statistical analysis. For example, Multivariate
linear regression models were used to examine the linear connection between sleep patterns,
dietary fiber intake, with liver fibrosis. Fitted smoothing curves and threshold effect analysis
were used to describe the nonlinear relationship, etc.
- A two-part linear regression model was also used to estimate threshold effects.
- Nothing was mentioned about the participant’s age, sex, etc. in the abstract.
In the Introduction section:
8. Besides the statement about MASLD and ALI, try to provide a summarized description of
The National Health and Nutrition Examination Survey (NHANES) in the background section
rather than in the methodology 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 a few examples of laboratory
components.”.
9. 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, doi.org/10.1007/s13679-024-00574-z).
In the Methods section:
10. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
11. What do you think about the following cases, shall be excluded from the study?
• Pregnant women,
• patients under 18 years of age,
• chronic heavy alcohol drinkers “more than 40 grams a day for men and 20 grams a day for
women”, patients with hepatobiliary cancers,
• patients with viral hepatitis like HBV or HCV,
• patients with chronic autoimmune hepatitis,
• Wilson disease,
• Hemochromatosis,
• Patients used steatogenic drugs like Amiodarone, Valproic Acid, and Tetracycline,
antiretroviral medications, disease-modifying anti-rheumatic medication like methotrexate, or
medications used to treat MASLD like vitamin E, and thiazolidinediones. Patients receiving
metformin, glucagon-like peptide-1 (GLP-1) agonists, or sodium-glucose cotransporter-2
(SGLT2) Inhibitors were also excluded.
12. How MASLD was diagnosed?
• By questionnaire, or
• By Imaging, including “ultrasonography (US)”, “computed tomography (CT)”, and “magnetic
resonance imaging (MRI)”, which are often used to diagnose incidentally when routine liver
function lab shows abnormal biochemical test results. A liver biopsy is required to detect NASH
to determine the fibrosis advancement.
13. How Fibrosis score, CAP, and LSM were calculated?
14. What was the source of the covariate data?
15. Statistical analysis:
In the Results section:
16. 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.
• In Tables 1 and 2
- what is the statistical test used to compare the two groups? The Mann–Whitney U test is a
nonparametric test and involves the summation of ranks. The Mann–Whitney U test is applied
to independent samples. T-test is used to compare the mean of a continuous variable between
a maximum of 2 groups.
- Abbreviations should be mentioned under the table.
• In Tables 3 and 4
- Please discuss the following: “Three logistic regression models were employed, with varying
levels of adjustment for potential confounders. Model 1 was unadjusted for covariates, while
Model 2 included adjustments for age, sex, and race. Model 3 was further adjusted for education,
marital status, PIR, BMI, alcohol intake, smoking status, physical activity, hypertension,
diabetes, high cholesterol levels, coronary heart disease, stroke, and cancer.” Could you please
explain how covariates were categorized? Why such diseases were excluded (hypertension,
diabetes, high cholesterol levels, coronary heart disease, stroke, and cancer)?
- The generalized additive model and smoothed curve testing should be used to assess the
nonlinear relationship.
17. No need to repeat results between tables and the result section
18. Subgroup analyses must be performed to evaluate the effect of circadian syndrome on
gallstones 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).
19. What about Quartile cut-off values?
20. Log2 logarithmic transformation shall be analyzed.
In the Discussion section:
21. 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.
22. Managing ALI. Please discuss this in detail.
23. Discuss the novelty of your study in the notion of others
(doi: 10.1002/jcsm.13032, doi.org/10.1002/ags3.12815).
24. Diseases diagnosis depending only on a questionnaire is to be considered one of the main
weaknesses.
In the conclusion section:
25. Conclusions aren’t simply an overview of a paper. Instead, they should reiterate why your
research is important.