JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-04058-9 (2025)

Title: Features on Contrast-Enhanced Computed Tomography for Predicting Recurrent
Esophageal Variceal Bleeding in Patients with Hepatocellular Carcinoma
Version: 3 Date: 20 Apr 2025
Reviewer's report:
This study is about the prediction of rebleeding of esophageal varices by Contrast-enhanced
computed tomography.
Although the results from the present study are interested me very much, I would like to make
the following comments because there are some concerns which should be reconsidered and
revised.
Major Revisions
1. The presence or absence of additional treatment (elective treatment) is extremely important in
analyzing long-term outcomes, especially variceal rebleeding. following endoscopic hemostasis
of esophageal variceal bleeding. In actual clinical practice, there are few cases that end with
emergency hemostasis alone, and in many cases, the indication and necessity of additional
treatment might be determined based on the prognosis predicted by each scoring system at the
time of esophageal variceal bleeding or after the hemostatic treatment. Detailed information on
additional treatment and additional analysis using this information should be presented.
2. The bleeding risk of esophageal varices is the red color (RC) sign on endoscopy.
However, RC sign during endoscopic treatment was not evaluated in this study.
3. The presence of gastric varices and para-esophageal veins should be considered.
4. Consider the staging of hepatocellular carcinoma between the two groups.
5. The effect of antiplatelet and anticoagulant drugs on rebleeding should be examined in portal
vein thrombosis.
Minor Revisions
none
Review for 10.1186/s12876-025-04058-9 (2025)

Title: Features on Contrast-Enhanced Computed Tomography for Predicting Recurrent
Esophageal Variceal Bleeding in Patients with Hepatocellular Carcinoma
Version: 4 Date: 11 May 2025
Reviewer's report:
This paper has been correctly revised to address the points raised, so I have no additional
comments.
Review for 10.1186/s12876-025-04058-9 (2025)

Title: Features on Contrast-Enhanced Computed Tomography for Predicting Recurrent
Esophageal Variceal Bleeding in Patients with Hepatocellular Carcinoma
Version: 4 Date: 13 May 2025
Reviewer:  Hiroki Minamiguchi
Reviewer's report:
I appreciate your corrections to my points.
However, let me confirm a few points.
About comments
7: You had not corrected the abbreviation for TACE.
8: 'while there was a statistically significant association that patients with a previous EV bleeding
episode would have a smaller EV size on CT than the cutoff of 9.5 mm (p = 0.031, Chi-square
test).' Where in the text is the statement or data on which it is based?
9. You had not corrected the abbreviation for TIPS.
11.  Why did you remove these from your table of abbreviations?
14. 'However, endoscopy is still the gold standard for both the evaluation and treatment of
esophageal varices for real clinical condition' 'for real clinical condition' is an infrequently used
and unclear expression. Does your description imply 'for clinical symptoms' or 'in actual clinical
practice'
Review for 10.1186/s12876-025-04138-w (2025)

Title: Early assessment of treatment response in primary biliary cholangitis: key to timely
management
Version: 2 Date: 01 Mar 2025
Reviewer's report:
The purpose of this study was to investigate predictors of complete biochemical response (CBR)
at month 12 and the conclusion of follow-up in patients with primary biliary cholangitis (PBC)
receiving ursodeoxycholic acid (UDCA), which presented many very interesting findings. And
the author has seriously addressed the editor's comments. I believe this article can be accepted
after some language refinement.
Review for 10.1186/s12876-025-04138-w (2025)

Title: Early assessment of treatment response in primary biliary cholangitis: key to timely
management
Version: 2 Date: 06 May 2025
Reviewer's report:
1. Were hepatitis B, hepatitis C and MAFLD included in the exclusion criteria?
2. In Table 5, why was there no significant difference in ALT at diagnosis and a significant
difference in AST? Also, please state based on that the disease was PBC.
Review for 10.1186/s12876-025-04138-w (2025)

Title: Early assessment of treatment response in primary biliary cholangitis: key to timely
management
Version: 4 Date: 03 Jul 2025
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have made a sincere effort to address the concerns
raised during the second  review. They have clarified the definition of the primary outcome and
standardized the terminology throughout the manuscript (e.g., use of "complete biochemical
response" and "at last check-up"), which improves clarity for the reader. These revisions enhance
the transparency and consistency of the outcome reporting
ADDITIONAL REQUESTS/SUGGESTIONS:
The authors have removed original Table 4 as well as original Figures 2 and 3 and this helps to
reduce the clutter and adds to the understanding of the data. I am happy with the rebuttal.
Review for 10.1186/s12876-025-04184-4 (2025)

Title: Global, Regional, and National Burden of Colorectal Cancer in the Elderly (Aged >60
Years): A Comprehensive Analysis Across 204 Countries and Territories (1990-2021)
Version: 1 Date: 07 Jun 2025
Reviewer's report:
I commend the authors for conducting a thorough and ambitious global analysis of CRC
trends in the elderly population using the GBD 2021 dataset. The manuscript presents a
robust epidemiological assessment with clear articulation of global, regional, and temporal
trends, supported by advanced statistical modeling techniques such as Joinpoint regression
and BAPC-INLA forecasting. The decomposition analysis offers valuable insights into how
population aging, growth, and epidemiological shifts have influenced CRC burden. However,
the manuscript would benefit from a more precise description of how elderly patients were
stratified and how age-standardization was executed, particularly in the context of international
comparability across differing population structures. Also, while the use of GBD data is
justified, the authors should acknowledge the limitations of relying solely on modeled estimates,
especially in low-resource regions where cancer registries are sparse or absent.
Moreover, while the Results section is numerically rich, the narrative could be enhanced by
drawing stronger comparisons between high- and low-SDI regions to better highlight global
disparities in CRC burden. A critical discussion of how future screening, treatment access,
and demographic shifts may differentially impact regions would strengthen the public health
relevance of the findings. Additionally, incorporating visual summaries such as trend heatmaps
or SDI-stratified forest plots may improve the clarity and reader engagement. For completeness,
I recommend the authors cite prior relevant population-based studies on CRC burden and
outcomes, particularly: Niu C, Zhang J, Sun M, Saeed H, Han Y, Okolo 3rd PI. Maternal and
perinatal outcomes of pregnant patients with colorectal cancer: a population-based study. J
Cancer Res Clin Oncol. 2023 Nov;149(15):14159-67. and Niu C, Zhang J, Lian J, Utsav J, Iyer
C, Low S, Saeed H, Zahid S, Okolo 3rd PI. Anatomical location, risk factors, and outcomes of
lower gastrointestinal bleeding in colorectal cancer patients: a national inpatient sample analysis
(2009–2019). Int J Colorectal Dis. 2023 Aug 4;38(1):205.
Review for 10.1186/s12876-025-04184-4 (2025)

Title: Global, Regional, and National Burden of Colorectal Cancer in the Elderly (Aged >60
Years): A Comprehensive Analysis Across 204 Countries and Territories (1990-2021)
Version: 1 Date: 08 Jun 2025
Reviewer's report:
Thanks for the opportunity to review the manuscript “Global, Regional, and National Burden of
Colon and rectum cancer in the Elderly Across 204 Countries and Territories” by Luo S
The authors wrote a manuscript on global trends in colorectal cancer in elderly patients,
utilizing global burden of disease data, joint point regression analysis, and Bayesian analysis for
projections. I congratulate the authors on putting in the time and effort to produce this important
work. Overall, authors present an important message to convey, that optimizing screening
strategies in the elderly population is a necessity.
Abstract – cite the age interval defining elderly adults in the background, as elderly patients (60
years old and older).
Results: spell BAPC
Figure 4 is incomplete; the variable box “epidemiological…”
In the discussion, the authors note that greater immunotherapy availability in high SDI countries
has a positive impact. However, the use of PD1 inhibitors/immunotherapy is too recent to have
influenced any trends, despite its promise. This warrants a brief acknowledgment.
The authors wrote: “This could result in inaccuracies when estimating the true burden of elderly
hip fractures.” Please rewrite this; the paper is not about hip fractures.
Review for 10.1186/s12876-025-04184-4 (2025)

Title: Global, Regional, and National Burden of Colorectal Cancer in the Elderly (Aged >60
Years): A Comprehensive Analysis Across 204 Countries and Territories (1990-2021)
Version: 1 Date: 20 Jun 2025
Reviewer's report:
I commend the authors for their efforts in addressing an important topic and for assembling
a comprehensive dataset and analytical framework. Given the complexity and breadth of the
methodology, I am unable to independently verify the accuracy of the underlying data or
analyses, which may also be beyond the intended scope of this review. However, assuming the
soundness of the data and methodology, I generally support the scope and conclusions presented.
I offer the following minor comments for the authors’ consideration:
1. Clarification on Standard Population Used for Age-Standardization
Age-standardized rates are typically used to facilitate comparisons across populations over time
or between geographic regions. For GLOBOCAN data, the 1966 Segi–Doll World Standard
Population is commonly employed. Based on the appendix, it appears that the authors used
the 2021 Global Burden of Disease (GBD) world population instead. If so, I suggest explicitly
stating the standard population used in the Methods section and providing a rationale for this
choice.
2. Clarification on Hereditary CRC Syndromes in the Discussion
In the Discussion section, the authors state:
“Additionally, the timely diagnosis and treatment of hereditary CRC syndromes, such as Lynch
Syndrome and familial adenomatous polyposis, in high-SDI regions may also contribute to the
declining trend in elderly CRC incidence…”
While early diagnosis and intervention for hereditary CRC syndromes may influence overall
trends, conditions like Lynch Syndrome and FAP are typically diagnosed in younger individuals,
often under the age of 50. Given that the manuscript focuses on individuals aged 60 and older, I
recommend revising or qualifying this statement to better reflect age-related incidence patterns.
3. Potential Typographical Error in Limitations
In the Limitations section, the manuscript states:
“This could result in inaccuracies when estimating the true burden of elderly hip fractures.”
This appears to be unrelated to the main topic of the manuscript and may have been included
inadvertently. If so, please revise or remove for clarity.
4. In Figure 4, some of the letters in the labels appear to be cut off or incomplete. Please revise
the figure to ensure that all text elements are fully visible and legible.
Review for 10.1186/s12876-025-04184-4 (2025)

Title: Global, Regional, and National Burden of Colorectal Cancer in the Elderly (Aged >60
Years): A Comprehensive Analysis Across 204 Countries and Territories (1990-2021)
Version: 3 Date: 14 Jul 2025
Reviewer's report:
Thank you for the opportunity to review the paper titled "Global, Regional, and National Burden
of Colorectal Cancer in the Elderly (Aged >60 Years): A Comprehensive Analysis Across 204
Countries and Territories (1990-2021)" by  Luo S et al.
The authors answered the requests satisfactorily. I have no further recommendations.
Review for 10.1186/s12876-025-04194-2 (2025)

Title: Dynamic Changes in Liver Stiffness Measurement by 2D Shear-wave Elastography
Predict Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Well-controlled
Viremia: A Retrospective Study
Version: 2 Date: 12 Apr 2025
Reviewer's report:
Although the idea of this study is very challenging to accurately predict the risk of HCC
in patients with well controlled viremia trying to create a new model, I have some critical
comments:
-In the methodology; The study design isn’t clear, and it should be rephrased to be more
understandable.
-the authors mentioned that there are 45 cirrhotic cases out of 303 total cases and then in Figure
1, you subclassified the 303 patients into 276 without HCC and 27 with HCC without revealing
the liver status of each group? So between 27 patients how many was cirrhotic?
- the number of  patients whom developed HCC (27 patients) is too small to validate the
conclusion as well as the model.
-To evaluate the dynamic changes in the LSM for the patients; you need to set a criteria for
follow up and duration to validate your results , so what was the time line for the follow up and
how you select the cut off value (I mean the number of the visits and its timing and the overall
follow up period).
-In the conclusion; you highlighted that you set a novel model , this model should be well
demonstrated in the results section
-The article need English editing.
Review for 10.1186/s12876-025-04194-2 (2025)

Title: Dynamic Changes in Liver Stiffness Measurement by 2D Shear-wave Elastography
Predict Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Well-controlled
Viremia: A Retrospective Study
Version: 2 Date: 18 Apr 2025
Reviewer:  Mohamed Elbasiony
Reviewer's report:
"Dynamic Changes in Liver Stiffness Measurement by 2D Shear-Wave Elastography Predict
HCC in CHB Patients with Well-Controlled Viremia"
I read the manuscript with interest. The study retrospectively analyzes 303 chronic hepatitis B
(CHB) patients (including 45 cirrhotic patients) with well-controlled viremia (HBV DNA <100
IU/mL sustained for >6 months) from 2016 to 2020. Patients underwent follow-up every 3–6
months with 2–11 reliable liver stiffness measurements (LSMs) via 2D shear-wave elastography
(SWE). While the work addresses an important clinical question, I have the following comments
and suggestions to improve clarity and interpretation:
Methodology – Interval Between LSMs:
The manuscript states that the interval between the first and last LSM ranged from 23 to
48 months. Such a wide variability in follow-up durations could introduce heterogeneity in
assessing dynamic LSM changes. Could the authors clarify how this variability was addressed
statistically and whether it may have influenced the predictive accuracy of LSM trends for HCC
development?
HCC Incidence Discrepancy:
The study reports that 27/303  patients developed HCC during follow-up. This incidence appears
notably higher than the widely cited annual HCC rates in non-cirrhotic (#1%) and cirrhotic (#2–
3%) CHB populations. Could the authors discuss potential reasons for this discrepancy? For
instance, were there high-risk subgroups?
Cohort Timeline Consistency:
The Methods section mentions 609 CHB patients who underwent 2D SWE between 2016 and
2020, but the Results describe a 7-year cumulative HCC incidence. This raises questions about
the timeline of enrollment, follow-up duration, and cohort selection. Please clarify how the 7-
year analysis aligns with the 2016–2020
Missing HBeAg Status Data:
HBeAg status (positive/negative) is a well-established factor influencing HBV-related
outcomes, including HCC risk. However, patient characteristics do not include HBeAg status.
Could the authors provide this information and assess its potential confounding effect on HCC
incidence in their cohort?
Review for 10.1186/s12876-025-04194-2 (2025)

Title: Dynamic Changes in Liver Stiffness Measurement by 2D Shear-wave Elastography
Predict Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Well-controlled
Viremia: A Retrospective Study
Version: 2 Date: 22 Apr 2025
Reviewer:  Suzan Hamed
Reviewer's report:
In this article the authors studied the capability of using dynamic changes in liver stiffness
measurements for chronic HBV patients with sustained controlled Viremia in predicting HCC
development.
This is a good study.
However, I have few comments.
1-The authors mentioned at the methods section line 140 that "Cirrhosis was clinically diagnosed
in patients who met the following criteria: (a) ultrasound findings suggestive of cirrhosis, (b)
serum albumin < 35 g/L, PLT < 100 × 109/L, international normalized ratio (INR) > 1.3 or
prolonged prothrombin time, and AST-to-PLT ratio index > 2 (meeting 2 or more of the above
criteria), and (c) evidence of portal hypertension."
They also mentioned that the number of cirrhotic patients was only 45.
They need to expand the definition of cirrhosis to include all F4 patients and also need to add to
them all patients with advanced fibrosis (F3) as all these patients have increased risk for HCC
development.
2- The authors need to clarify if all the patients were followed up for the same period of time or
there was significant difference in the duration of follow up for different patients, as the more
prolonged infection may be a confounding factor for the development of HCC.
3-The authors mentioned that they developed nomogram model for HCC prediction and
Comparison of the performance of the new model and previous models and compared the
performance of their new model with that of other models like SAGE-B, HCC-RESCUE and
REACH-B II.  I think the authors need to validate these results on a larger sample size.
Review for 10.1186/s12876-025-04194-2 (2025)

Title: Dynamic Changes in Liver Stiffness Measurement by 2D Shear-wave Elastography
Predict Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Well-controlled
Viremia: A Retrospective Study
Version: 3 Date: 14 May 2025
Reviewer:  Mohamed Elbasiony
Reviewer's report:
Thank you for your response.
Review for 10.1186/s12876-025-04194-2 (2025)

Title: Dynamic Changes in Liver Stiffness Measurement by 2D Shear-wave Elastography
Predict Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Well-controlled
Viremia: A Retrospective Study
Version: 4 Date: 04 Jul 2025
Reviewer:  Mohamed Elbasiony
Reviewer's report:
satisfied by the responses ... accepted
Review for 10.1186/s12876-025-04194-2 (2025)

Title: Dynamic Changes in Liver Stiffness Measurement by 2D Shear-wave Elastography
Predict Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Well-controlled
Viremia: A Retrospective Study
Version: 5 Date: 18 Jul 2025
Reviewer's report:
Commendable effort
Review for 10.1186/s12876-025-03989-7 (2025)

Title: Impact of timing of endoscopy on clinical outcomes in cirrhotic patients with esophageal
variceal bleeding: a monocentric retrospective study from Vietnam
Version: 2 Date: 18 Apr 2025
Reviewer's report:
Comments on the manuscript by Khoa Nguyen Phuoc et al.
The authors investigated the impact of endoscopy timing on clinical outcomes in patients
presenting with gastrointestinal bleeding due to esophageal varices. The study excluded non-
esophageal bleeding. The study concludes that there is no statistically significant difference
in outcomes between early and delayed endoscopy. This topic has been addressed in several
retrospective and RCT studies.
Major Comments:
-Study Design: The retrospective, single-center nature of the study is a limitation and may affect
the generalizability of the findings.
-Authors need to specify how many patients in the cohort experienced renal injury, as this is a
relevant clinical factor that may influence outcomes.
- Authors need to add a decrease in hemoglobin concentration/ blood transfusion to the main
outcomes as not all cases require blood transfusion.
- Table 3: The authors are advised to include Child-Pugh Class C as a variable in the multivariate
logistic regression model assessing in-hospital mortality. This is a well-established predictor of
poor outcomes and should be accounted for.
-Table 3: Authors need to add endoscopic intervention or surgery and days of hospital admission
(# 5 days) to the logistic regression.
-The incidence of rebleeding during hospitalization or after should be reported as a main
outcome.
Review for 10.1186/s12876-025-03989-7 (2025)

Title: Impact of timing of endoscopy on clinical outcomes in cirrhotic patients with esophageal
variceal bleeding: a monocentric retrospective study from Vietnam
Version: 2 Date: 18 Apr 2025
Reviewer's report:
This study addresses an important clinical question regarding the optimal timing of endoscopy
in cirrhotic patients with EVB. Below is my review and recommendations for improvement:
Strengths#
Clinical Relevance: The study tackles a guideline-controversial issue with practical implications
for resource allocation and emergency care pathways.
Methodology:Use of propensity score matching (PSM) to address baseline confounders.Clear
definition of primary (5-day treatment failure) and secondary outcomes (mortality, ICU needs,
etc.).
Multivariate Analysis: Identifies independent predictors of mortality (e.g., Child-Pugh score),
aligning with established prognostic factors in cirrhosis.
Major Concerns
There have been similar reports recently, so this article lacks originality (Ref: Peng M, Bai
Z, Zou D, et al. Timing of endoscopy in patients with cirrhosis and acute variceal bleeding:
a single-center retrospective study. BMC Gastroenterol. 2023;23(1):219. Published 2023
Jun 26. doi:10.1186/s12876-023-02766-8).We suggest that the author conduct a prospective
randomized controlled study to provide high-level evidence.
Sample Size and Power:
No power calculation is provided. With a 1% absolute difference in 5-day treatment failure
(10.1% vs. 9%), the study may be underpowered to detect clinically meaningful differences. A
post-hoc power analysis is recommended.
Confounding Factors:
Key variables affecting outcomes in EVB (e.g., use of vasoactive drugs, antibiotics, or
resuscitation protocols) are not described. Differences in medical management between groups
could bias results.
Endoscopist expertise and technical variability (e.g., band ligation technique) are unaddressed.
Definition of "Timing":
The time from "admission" to endoscopy is used, but guidelines typically recommend timing
from "hematemesis" or "clinical presentation." Delays in hospital transfer or triage may
confound results.
Retrospective Design Limitations:
Selection bias (e.g., sicker patients may have received earlier endoscopy) is incompletely
mitigated by PSM. Unmeasured confounders (e.g., portal pressure, collateral circulation) remain
a concern.
Conclusion:reject.
Review for 10.1186/s12876-025-03989-7 (2025)

Title: Impact of timing of endoscopy on clinical outcomes in cirrhotic patients with esophageal
variceal bleeding: a monocentric retrospective study from Vietnam
Version: 3 Date: 29 Apr 2025
Reviewer's report:
The author has made revisions in accordance with the reviewers' comments. I think the current
version of the manuscript is acceptable.
Review for 10.1186/s12876-025-03989-7 (2025)

Title: Impact of timing of endoscopy on clinical outcomes in cirrhotic patients with esophageal
variceal bleeding: a monocentric retrospective study from Vietnam
Version: 3 Date: 05 May 2025
Reviewer:  Sergiu Marian Cazacu
Reviewer's report:
The authors have responded to the queries and observations contained in my first report. I have
no other comments to add.
Review for 10.1186/s12876-025-03989-7 (2025)

Title: Impact of timing of endoscopy on clinical outcomes in cirrhotic patients with esophageal
variceal bleeding: a monocentric retrospective study from Vietnam
Version: 3 Date: 12 May 2025
Reviewer's report:
The authors have satisfactorily addressed all of my previous comments and concerns. I have no
further suggestions or revisions.
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 0 Date: 10 May 2025
Reviewer's report:
Major Comment
• In the discussion section (pages 240–253), the explanation of the nonlinear association between
the HbA1c/HDL-C ratio and NAFLD—particularly for values below the inflection point of 1.43
—lacks clarity and may present a logical contradiction. The authors should clarify why NAFLD
risk appears to increase when the ratio is below 1.43, and ensure that the mechanistic explanation
aligns with the observed data.
Minor Comments
1. A brief overview of the NHANES dataset would improve accessibility for a broader
readership. Please clarify:
o What population the dataset represents
o How participants were selected
o Whether this was a cross-sectional or longitudinal dataset and how follow-up was conducted
if it’s a longitudinal dataset
2. For comorbid conditions such as hypertension (HTN), hepatitis B virus infection (HBV),
etc., please indicate whether diagnoses were determined by ICD-9/ICD-10 codes or survey
responses. If applicable, a supplemental table listing the specific diagnostic codes would enhance
transparency.
3. In Figure 1, please clarify the rationale for excluding patients with a history of chronic
hepatitis.
4. Address typographical and labeling issues—for example, should it be “ALL” or “All” in
Figure 1.
5. Please define the abbreviation of “RIP” as it appears in Line 125.
6. The rationale for dividing participants into tertiles based on the HbA1c/HDL-C ratio should
be explained. Why were tertiles chosen over quartiles or quintiles
7. A reference should be provided for the statement:“Data were weighted according to the
recommendations of guidelines published by the Centers for Disease Control and Prevention
(CDC).” (lines 117–178).
8. The presentation of data could be made more formal. For example, the sentence: “There
were 5,485 individuals in all, 44.67% of them being male and their mean age was 45.86 (18.32)
years” (lines 133–134) should clarify that (18.32) refers to the standard deviation (SD); In
line 85, the sentence: “We ignored minors under the age of 18 years (5867)”would be more
appropriately presented as:
“We excluded minors under the age of 18 years (n = 5,867).”
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 0 Date: 11 Jun 2025
Reviewer's report:
This manuscript evaluates the cross-sectional association between the HbA1c/HDL-C ratio and
non-alcoholic fatty liver disease (NAFLD) in non-diabetic adults using data from the NHANES
2017–2020 survey. The topic is interesting and potentially valuable for identifying novel non-
invasive indicators of NAFLD risk. However, several methodological concerns need to be
addressed. My comments are as follows:
1. The manuscript refers to "NAFLD," despite recent consensus recommending a shift toward
the term "metabolic dysfunction-associated steatotic liver disease (MASLD)." The rationale for
maintaining the outdated terminology is unclear. The authors should clarify their choice and
consider updating the terminology to align with current classification standards, unless there is
a compelling reason to retain NAFLD in the context of this dataset.
2. Methods (Line 88). The authors state that participants with heavy alcohol consumption
were excluded, but the cut-off values used to define "heavy" drinking are not reported. This
information should be explicitly stated.
3. Methods (Lines 100–101). The manuscript categorizes liver stiffness into stages (F2, F3,
F4), presumably based on the METAVIR score. This should be explicitly stated for clarity.
Furthermore, Reference 18 does not appear to support the liver stiffness cut-off values used for
staging fibrosis. The authors should provide an appropriate and validated reference to justify
the thresholds applied.
4. Methods (Line 109). The authors refer to "moderate activity" but do not explain how this
was defined or quantified. A clear operational definition, along with an appropriate reference,
should be added.
5. While the HbA1c/HDL-C ratio is the primary independent variable of interest, the rationale
for not including HbA1c and HDL-C as separate covariates in the statistical model is unclear.
It would be helpful to know whether the association between the ratio and NAFLD remains
significant when HbA1c and HDL-C are included individually in the model. The current
analysis does not address whether the observed association is driven primarily by one of the
components of the ratio. The authors should consider additional models that include these
covariates separately to clarify this point.
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 0 Date: 11 Jun 2025
Reviewer's report:
In this study, Mao et al. investigated the association between glycated hemoglobin/high-density
lipoprotein ratio and nonalcoholic fatty liver disease in a non-diabetic US population. While the
study presents an interesting perspective, there are some issues that should be addressed.
Major comments:
#1. The current study does not account for several important covariates that may influence the
results. Relevant variables such as waist circumference, waist-to-height ratio, dietary patterns,
physical activity levels, alcohol consumption, renal function markers (uric acid, creatinine,
BUN, eGFR), and the use of antihypertensive medications are all potential confounders. It is
strongly recommended that these variables be incorporated into the study.
#2. As the present study design appears to be cross-sectional or observational rather than a
longitudinal cohort study, it is methodologically inappropriate to infer causality or use terms
such as “risk.” Instead, the findings should be described in terms of associations or correlations.
#3. A thorough language and grammatical review by a native English speaker is highly
recommended.
Minor comments:
#1. I recommend specifying the study design in the title.
#2. I would like to inquire whether the appropriate sample size was calculated for this study. If
so, please include details regarding the sample size calculation in the methods section.
#3. I recommend providing a clear rationale for the study.
#4. Please specify the developer and the associated country for each software used in your
analysis.
#5. Please mention the statistical tests used to assess the normality of variables in your analysis.
#6. Please mention the method used for assessing all variables in method section :” TG, total
cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT),
aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGT), and albumin (Alb)”
#7. I suggest providing more detailed information on how height and weight were measured and
how BMI was calculated.
#8. Please provide the criteria used to define hypertension in your study.
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 1 Date: 29 Jun 2025
Reviewer's report:
The authors have adequately addressed most of my previous comments. However, the major
concern—the explanation of the non-linear association and the inflection point at a ratio of 1.43
—remains unresolved.
In particular, for HbA1c/HDL-C ratios below 1.043, the data appear counterintuitive. For
example, as shown in the figure 2 ( the main finding), patients with a ratio of 0.5 seem to have a
higher risk of NAFLD than those with a ratio of 1.0. This contradicts the general understanding
that a lower HbA1c and higher HDL-C (i.e., a lower ratio) typically indicate better metabolic
health.
The authors’ discussion—“At ratios below this inflection point, HbA1c/HDL-C was negatively
associated with NAFLD, suggesting that moderately higher ratios in this interval are instead
associated with a decreased risk of NAFLD. This trend may reflect a relatively healthy metabolic
state, i.e., good glycemic control (low HbA1c) and high HDL-C levels, when insulin sensitivity
is enhanced, hepatic lipid metabolism is balanced, and inflammation is low, which helps to
reduce hepatic lipid deposition.”—does not seem to adequately explain this paradox.
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 1 Date: 01 Jul 2025
Reviewer's report:
The manuscript has significantly improved. Thank you for your thoughtful revisions and effort.
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 1 Date: 13 Jul 2025
Reviewer's report:
My previous comments have been satisfactorily addressed.
I have no further comments. Thanks!
Review for 10.1186/s12876-025-04190-6 (2025)

Title: Association between glycated hemoglobin/high-density lipoprotein ratio and
nonalcoholic fatty liver disease in a U.S. nondiabetic population: a cross-sectional study based
on NHANES 2017-2020 data
Version: 2 Date: 20 Jul 2025
Reviewer's report:
My questions have been well addressed. No further comments
Review for 10.1186/s12876-025-04200-7 (2025)

Title: The value of fecal calprotectin measured by fluorescent immunochromatography assay
in evaluating clinical and endoscopic activity in ulcerative colitis
Version: 1 Date: 07 Jul 2025
Reviewer:  Maha M. Maher
Reviewer's report:
Dear Authors
Calprotectin is considered a significant biomarker in monitor patient with IBD and searching
for a significant accurate method for detection is an important issue in the field of inflammatory
bowel disease
The introduction cover most of the ideas ,as regard to methodology the authors classify patients
into groups according to disease activity ,they mentioned that they follow hospitalized patients
in certain durations
The question here is why patient in remission was hospitalized
This question should be answered to rule out  other causes of admission that could affect results.
Otherwise patients distribution, demographic data ang statistical analysis are sufficient
Results and analysis of data were Representative
Thanks
Review for 10.1186/s12876-025-04164-8 (2025)

Title: Epidemiologic and Clinical Profiles of Colorectal Cancer in Southern Egypt
Version: 3 Date: 14 May 2025
Reviewer:  Saeed Shaaban
Reviewer's report:
I think this paper focused on area of low research interest so publishing like this topic will be
helpful to get more data about this group of population
Review for 10.1186/s12876-025-04164-8 (2025)

Title: Epidemiologic and Clinical Profiles of Colorectal Cancer in Southern Egypt
Version: 3 Date: 22 May 2025
Reviewer's report:
The study highlights a very important problem in south of Egypt especially no available statistics
about the incidence of CRC  in southern Egypt.
I would like to thank all the authors for their study.
I have only one remark:
In the Results section 4th line 76.5% instead of 76/5%
Review for 10.1186/s12876-025-04164-8 (2025)

Title: Epidemiologic and Clinical Profiles of Colorectal Cancer in Southern Egypt
Version: 3 Date: 24 May 2025
Reviewer's report:
Methods:  We (ascertained ) .... the word ascertained should be changed.
Page 4 .... "during the (conduction)" should be changed. Not a suitable word.
Page 7.... should read we (analyzed) rates....
Page 9..... "Diagnosed CRC patients may be .....the changing population pyramid". How is this
sentence relevant?
Page 10..."are close in magnitude" ( change to: are similar)
Page 10... "Further, the similar rates between.....represents a rise....for females in this region."
Does it? Where are your stats?
Page 10.... "Over  one-quarter of .....compared to 17-21%"....Ref is 1997! I don't think a 28 year
old ref/study is useful here.
Page 11 ....:" so the missingness..." ( please rephrase this part. Change the word )
Page 12..."thus managing the bias in the date. This study however helps to fill......" ( suggested
change)
Conclusion : suggestion. Rephrase first two sentences.
Page 13: last sentence chould read..." to better track and treat different populations. "
Table 1 Demographics... It would be helpful to show Family hx as n=108 ( 17.7%) of your
sample and NOT as shown here.
Authors: kindly refer reader to appropriate tables.
Review for 10.1186/s12876-025-04146-w (2025)

Title: Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal
fibrostenotic strictures in patients with Crohn’s disease
Version: 3 Date: 13 Apr 2025
Reviewer's report:
Comments to the Authors
Intestinal fibrosis-associated stricture could lead to complications in patients with Crohn's
disease (CD). However, no ideal biomarkers are widely accepted for sequential monitoring
of fibrosis and disease progression. The study focuses on serum PRO-C16, which measures
the formation of type XVI collagen. PRO-C16 was significantly elevated in CD patients with
strictures and in an animal model of intestinal fibrosis. The findings in this study indicated that
PRO-C16 may serve as a biomarker of intestinal fibrosis. However, some concerns need to be
addressed.
1. This study showed PRO-16 was able to separate CD patients with strictures (B2) from CD
patients without strictures (B1 and B3). According to the literature, penetrating CD (B3) often
accompanies with intestinal stenosis (Jurgens M, Brand S, Laubender RP, et al. The presence
of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease
independent of the IL23R genotype. J Gastroenterol 2010;45:721-31). It is recommended to
explain this carefully.
2. In the section of INTRODUCTION, it would be beneficial to refer to additional evidence
of PRO-16 on IBD and gap in this field (the difference between the study and the previous
literature).
3. In Page 6 Line 127, please add the unit after “1”.
4. In Page 9, was PRO-16 associated with inflammatory indicators, such as C-reactive protein,
and erythrocyte sedimentation rate (ESR)?
5. In Table 1, CD patients with peri-anal disease are not included in this study, which may not
be representative of the real situation and affect the results.
6. In Table 1, it is recommended to add the medical treatment and the association with PRO-16.
7. In Table 1, some percentage values in Cohort 2 are missing.
8. In Page 9, the study mentioned that PRO-C16 did not correlate with disease activity, disease
location, gender, or age, but PRO-C16 was numerically elevated in CD patients with active
disease compared to inactive disease. I think the data should be added in the Supplementary
Materials.
9. In Page 11, it seems that the study also investigated PRO-C16 serum levels in CD patients
with inactive and active disease activity. However, the data of the result is missing.
10. In Page 14 Line 231, the study mentioned that the PRO-C16 marker measures active
fibrogenesis, which is not convincing.
11. In Figure 4, it is recommended to show the statistical data. Ideally, fibrosis in the later stage
would be more dominant.
12. The current form of Figure 5 is confusing. It is recommended to add any annotations (such
as day 7 or day 14) in the figure. Besides, it would be better to put Figure 5C and 5D in the
Supplementary Materials.
13. In the figure legends and relevant texts, please add the sample size of each group.
14. It is recommended to use colors in all figures to make them clear.
Review for 10.1186/s12876-025-04146-w (2025)

Title: Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal
fibrostenotic strictures in patients with Crohn’s disease
Version: 4 Date: 28 Jun 2025
Reviewer's report:
Both in "Study highlights" and in the "Conclusion" authors state that "PRO-C16 serum assay
may be a potential biomarker for intestinal fibrosis ", while in the abstract they state that "PRO-
C16 may be employed as a marker of intestinal fibrosis in CD".
The detail of being a POTENTIAL biomarker is, in my opinion, very important and should figure
also in the abstract, thus avoiding the reader to misunderstand the conclusion of this  study.
Aside from this detail, I have no further comments.
Review for 10.1186/s12876-025-04146-w (2025)

Title: Serological assessment of PRO-C16 (type XVI collagen formation) reflects intestinal
fibrostenotic strictures in patients with Crohn’s disease
Version: 4 Date: 30 Jun 2025
Reviewer's report:
I thank the authors for their responses. Please fin below some minor points:
“Based on these findings by Ratzinger et al.[5] and Jensen et al.[24], demonstrating type XVI
collagen’s relevance in patients with UC and the lack of a biomarker for intestinal fibrosis,
especially in CD patients. Therefore, we wanted to investigate PRO-C16 as a marker of intestinal
fibrostenotic strictures in Crohn’s disease patients. “ These last sentences of the introduction are
not well written in my opinion.
-“Even though PRO-C16 did not reach statistical significance between the inactive vs. active
CD patients based on the CDAI score, we still observed numerically elevated PRO-C16 serum
levels in the active group. However, type XVI collagen has been shown to increase the
expression and activation of MMP-9 locally in tissue at the site of insult by immune cells,
e.g., macrophages and neutrophils[31]”. This could explain the elevated levels of PRO-C16
observed in Crohn’s disease patients with active disease, as MMP-9 tissue expression leads
to chronic intestinal mucosal damage[14–20, 32, 33]. This process is thought to be facilitated
by type XVI collagen’s ability to maintain adhesion of intestinal subepithelial myofibroblasts,
thus increasing the pathological development of intestinal fibrostenotic strictures[5]. “These
sentences are highly speculative and not very comprehensible. The link between MMP9 and
PRO-C16 is not explained. I suggest removing this part.
Review for 10.1186/s12876-025-04169-3 (2025)

Title:  Efficacy of Prophylactic Dexamethasone in Reducing Post-Embolization Syndrome
Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A
Systematic Review and Meta-Analysis
Version: 0 Date: 24 Jun 2024
Reviewer's report:
This study evaluates the efficacy of prophylactic dexamethasone in reducing post-embolization
syndrome (PES) symptoms—abdominal pain, fever, nausea, and vomiting—following TACE
for unresectable hepatocellular carcinoma.  This meta-analysis of five trials showed significant
reductions in the incidence of these symptoms,  suggesting that dexamethasone is effective in
preventing and alleviating PES.
1. A comprehensive search is required for the meta-analysis. The search terms are relatively
incomplete and not standardized in current version of the manuscript. I supposed that a complete
search strategy could be conducted and attached as a supplement.
2.  Could more data on patient baseline characteristics be provided in Table 1?
3.  As the treatment of HCC progresses towards an era of integrated TACE, immunotherapy,
and targeted therapy (eClinicalMedicine, 2024, 72:102622; Signal Transduct Target Ther, 2023,
8(1): 58; Eur Radiol, 2023, 33(12): 8669-81), the authors are encouraged to enhance their
discussion on the role of dexamethasone in managing PES within these combination therapies,
as well as its potential effects on immunotherapy outcomes.
4. Could authors add a correlation analysis chart detailing the effect of dexamethasone on PES
and the proportion of the study population with HBV infection?
Review for 10.1186/s12876-025-04169-3 (2025)

Title:  Efficacy of Prophylactic Dexamethasone in Reducing Post-Embolization Syndrome
Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A
Systematic Review and Meta-Analysis
Version: 0 Date: 27 Jun 2024
Reviewer:  Chenxi Yu
Reviewer's report:
1. Some of the references cited are outdated; it is suggested to update the references.
2. The symptoms of postembolization syndrome include fatigue, anorexia, fever, nausea,
vomiting, and pain. However, the article only analyzes fever, nausea, vomiting, and pain. The
discussion mentions evidence of dexamethasone improving nausea and vomiting, but it does not
elaborate on the potential mechanisms by which dexamethasone may improve fever and pain.
It is recommended to supplement the relevant content.
3. The statement "p=0.00" in the article is inaccurate; it is suggested to revise it to "p < 0.001".
Review for 10.1186/s12876-025-04169-3 (2025)

Title:  Efficacy of Prophylactic Dexamethasone in Reducing Post-Embolization Syndrome
Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A
Systematic Review and Meta-Analysis
Version: 0 Date: 01 Jul 2024
Reviewer:  Haohuan Tang
Reviewer's report:
PES is the most common adverse reaction after TACE, and the authors, through a systematic
review and meta-analysis of RCT studies, described the perioperative prophylactic use of
dexamethasone, which relieves abdominal pain, fever, nausea, and vomiting This is a practical
guide for clinical work, but there are some limitations.
1, prophylactic use of dexamethasone, which relieves the incidence of symptoms such as
abdominal pain, fever, nausea, and vomiting, but the study does not seem to mention the grade
of adverse effects; did the use of dexamethasone improve the grading of AEs?
2, The authors compared the effects of embolization materials, dexamethasone dose, and
observation time on the results of the studies in subgroup analyses. In addition to this, conditions
such as the degree of embolization and tumor load were, in some studies, influential factors in the
occurrence of PES. In addition, in several of the RCT studies analyzed in the article, there were
differences in the type of chemotherapy drugs used. What do the authors make of these issues?
3, The studies included in the article focused on conventional TACE and reported less on the
safety of dexamethasone, which the authors could not quantify. Therefore the generalization of
study findings needs to be done with caution.
4, The language needs to be further trimmed and embellished.