Title: Global Burden of Gallbladder and Biliary Diseases (1990-2021) with Healthcare
Workforce Analysis and Projections to 2035
Version: 3 Date: 15 Mar 2025
Reviewer's report:
This manuscript provides a comprehensive epidemiological analysis of gallbladder and biliary
tract diseases based on Global Burden of Disease Study (GBD) 2021 data. The study
systematically evaluates long-term trends in incidence, prevalence, disability-adjusted life
years (DALYs), and mortality, alongside projections up to 2035 using the Bayesian Age-
Period-Cohort (BAPC) model.  The research is well-structured, and the statistical methods are
appropriately applied. However, there are methodological and interpretative limitations that
need to be addressed before the manuscript is suitable for publication.
1. The manuscript attributes the increase in absolute case numbers primarily to population
aging and growth. However, other key risk factors (e.g., obesity, metabolic disorders, lifestyle
changes) are not sufficiently discussed.
2. The manuscript relies entirely on GBD 2021 data without a critical evaluation of its
limitations. Potential concerns include: variability in data quality across different countries;
the possibility of underestimation of disease burden in regions with limited healthcare access;
potential biases introduced by data extrapolation methods. The "Limitations" section should
explicitly acknowledge these constraints and discuss their potential impact on the study’s
conclusions.
3. The study employs the BAPC model for projections, but it does not evaluate the accuracy
of the model or discuss potential sources of error. No comparison with alternative forecasting
methods is provided. The "Methods" section should briefly justify the choice of the BAPC
model, while the "Discussion" section should include its limitations and uncertainties.
4. The manuscript does not discuss how improvements in medical treatments, such as the
widespread adoption of laparoscopic cholecystectomy, may have influenced the observed trends
in DALYs and mortality. Please add a brief discussion  on the impact of improved diagnostics
and surgical treatments on mortality reduction would strengthen the interpretation of results.
5. In some parts of the text, it is unclear which changes in disease burden are due to demographic
factors (aging and population growth) versus epidemiological trends (true changes in disease
risk). Please clarify and distinguish between absolute case increases and age-standardized rates
when reporting trends. Also, it is important to explicitly state where increased case numbers are
due to demographic changes rather than increased disease incidence.
I would like to once again thank the authors for the opportunity to review their publication.
After addressing the raised questions and making the necessary revisions, the manuscript may
be considered for publication.
Title: Global Burden of Gallbladder and Biliary Diseases (1990-2021) with Healthcare
Workforce Analysis and Projections to 2035
Version: 3 Date: 15 Mar 2025
Reviewer's report:
This manuscript provides a comprehensive epidemiological analysis of gallbladder and biliary
tract diseases based on Global Burden of Disease Study (GBD) 2021 data. The study
systematically evaluates long-term trends in incidence, prevalence, disability-adjusted life
years (DALYs), and mortality, alongside projections up to 2035 using the Bayesian Age-
Period-Cohort (BAPC) model.  The research is well-structured, and the statistical methods are
appropriately applied. However, there are methodological and interpretative limitations that
need to be addressed before the manuscript is suitable for publication.
1. The manuscript attributes the increase in absolute case numbers primarily to population
aging and growth. However, other key risk factors (e.g., obesity, metabolic disorders, lifestyle
changes) are not sufficiently discussed.
2. The manuscript relies entirely on GBD 2021 data without a critical evaluation of its
limitations. Potential concerns include: variability in data quality across different countries;
the possibility of underestimation of disease burden in regions with limited healthcare access;
potential biases introduced by data extrapolation methods. The "Limitations" section should
explicitly acknowledge these constraints and discuss their potential impact on the study’s
conclusions.
3. The study employs the BAPC model for projections, but it does not evaluate the accuracy
of the model or discuss potential sources of error. No comparison with alternative forecasting
methods is provided. The "Methods" section should briefly justify the choice of the BAPC
model, while the "Discussion" section should include its limitations and uncertainties.
4. The manuscript does not discuss how improvements in medical treatments, such as the
widespread adoption of laparoscopic cholecystectomy, may have influenced the observed trends
in DALYs and mortality. Please add a brief discussion  on the impact of improved diagnostics
and surgical treatments on mortality reduction would strengthen the interpretation of results.
5. In some parts of the text, it is unclear which changes in disease burden are due to demographic
factors (aging and population growth) versus epidemiological trends (true changes in disease
risk). Please clarify and distinguish between absolute case increases and age-standardized rates
when reporting trends. Also, it is important to explicitly state where increased case numbers are
due to demographic changes rather than increased disease incidence.
I would like to once again thank the authors for the opportunity to review their publication.
After addressing the raised questions and making the necessary revisions, the manuscript may
be considered for publication.
Please review this paper.
user
Title: Global Burden of Gallbladder and Biliary Diseases (1990-2021) with Healthcare
Workforce Analysis and Projections to 2035
Version: 3 Date: 15 Mar 2025
Reviewer's report:
This manuscript provides a comprehensive epidemiological analysis of gallbladder and biliary
tract diseases based on Global Burden of Disease Study (GBD) 2021 data. The study
systematically evaluates long-term trends in incidence, prevalence, disability-adjusted life
years (DALYs), and mortality, alongside projections up to 2035 using the Bayesian Age-
Period-Cohort (BAPC) model.  The research is well-structured, and the statistical methods are
appropriately applied. However, there are methodological and interpretative limitations that
need to be addressed before the manuscript is suitable for publication.
1. The manuscript attributes the increase in absolute case numbers primarily to population
aging and growth. However, other key risk factors (e.g., obesity, metabolic disorders, lifestyle
changes) are not sufficiently discussed.
2. The manuscript relies entirely on GBD 2021 data without a critical evaluation of its
limitations. Potential concerns include: variability in data quality across different countries;
the possibility of underestimation of disease burden in regions with limited healthcare access;
potential biases introduced by data extrapolation methods. The "Limitations" section should
explicitly acknowledge these constraints and discuss their potential impact on the study’s
conclusions.
3. The study employs the BAPC model for projections, but it does not evaluate the accuracy
of the model or discuss potential sources of error. No comparison with alternative forecasting
methods is provided. The "Methods" section should briefly justify the choice of the BAPC
model, while the "Discussion" section should include its limitations and uncertainties.
4. The manuscript does not discuss how improvements in medical treatments, such as the
widespread adoption of laparoscopic cholecystectomy, may have influenced the observed trends
in DALYs and mortality. Please add a brief discussion  on the impact of improved diagnostics
and surgical treatments on mortality reduction would strengthen the interpretation of results.
5. In some parts of the text, it is unclear which changes in disease burden are due to demographic
factors (aging and population growth) versus epidemiological trends (true changes in disease
risk). Please clarify and distinguish between absolute case increases and age-standardized rates
when reporting trends. Also, it is important to explicitly state where increased case numbers are
due to demographic changes rather than increased disease incidence.
I would like to once again thank the authors for the opportunity to review their publication.
After addressing the raised questions and making the necessary revisions, the manuscript may
be considered for publication.
assistant