Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 4 Date: 13 Mar 2025
Reviewer:  Avinash Tiwari
Reviewer's report:
Dear Authors,
I appreciated the opportunity to review your systematic review and meta-analysis titled
“Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis.” While your work is
informative and contributes valuable insights to the field, I have several concerns that should be
addressed to enhance the quality of the manuscript:
Liver Biopsy and Modified Histological Activity Index (mHAI): The manuscript does not
provide information regarding liver biopsy findings or the use of the modified histological
activity index (mHAI). Given that, in autoimmune hepatitis (AIH), clinical remission typically
precedes biochemical and histological remission—and that histological remission is often
assessed via mHAI—it is recommended that you discuss this aspect. Incorporating mHAI data is
vital, as many patients who achieve biochemical remission may still exhibit histological disease
activity, a fact emphasized in current guidelines.
Cost-Benefit Analysis: Although it is acknowledged that mycophenolate mofetil (MMF) is
associated with fewer side effects compared to azathioprine (AZA), the economic implications
of long-term immunosuppressive therapy are also crucial. A cost-benefit analysis would offer
important insights into the overall feasibility and affordability of MMF as a first-line treatment
option in clinical practice.
CTP/MELD Scores: There is a lack of information regarding the Child-Turcotte-Pugh (CTP)
and Model for End-Stage Liver Disease (MELD) scores of the patients included in the analysis.
These scores are essential for evaluating the severity of liver disease and could influence
treatment outcomes. It is recommended that you include this information to better contextualize
your findings.
Propensity-Matched Trial Considerations: One of the studies included in the analysis is based
on a propensity-matched trial. Please discuss potential confounders inherent in such a study
design, as these could affect the overall results of the meta-analysis. An exploration of how these
confounders might skew the findings will strengthen the validity of your conclusions.
Search Strategy Details: The search strategy would benefit from the inclusion of the date and
time of the searches performed. This information is essential for reproducibility and provides
important context regarding the literature coverage.
PROSPERO Registration: The manuscript does not indicate whether the review protocol
was registered on PROSPERO. Given the importance of protocol registration in ensuring
transparency and reducing reporting bias, please provide details regarding PROSPERO
registration, or explain why registration was not pursued.
I kindly request that you review and revise the manuscript to address these concerns.
Incorporating these points will significantly enhance the methodological transparency and
overall rigor of your study.
Sincerely,
Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 4 Date: 13 Mar 2025
Reviewer:  Avinash Tiwari
Reviewer's report:
Dear Authors,
I appreciated the opportunity to review your systematic review and meta-analysis titled
“Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis.” While your work is
informative and contributes valuable insights to the field, I have several concerns that should be
addressed to enhance the quality of the manuscript:
Liver Biopsy and Modified Histological Activity Index (mHAI): The manuscript does not
provide information regarding liver biopsy findings or the use of the modified histological
activity index (mHAI). Given that, in autoimmune hepatitis (AIH), clinical remission typically
precedes biochemical and histological remission—and that histological remission is often
assessed via mHAI—it is recommended that you discuss this aspect. Incorporating mHAI data is
vital, as many patients who achieve biochemical remission may still exhibit histological disease
activity, a fact emphasized in current guidelines.
Cost-Benefit Analysis: Although it is acknowledged that mycophenolate mofetil (MMF) is
associated with fewer side effects compared to azathioprine (AZA), the economic implications
of long-term immunosuppressive therapy are also crucial. A cost-benefit analysis would offer
important insights into the overall feasibility and affordability of MMF as a first-line treatment
option in clinical practice.
CTP/MELD Scores: There is a lack of information regarding the Child-Turcotte-Pugh (CTP)
and Model for End-Stage Liver Disease (MELD) scores of the patients included in the analysis.
These scores are essential for evaluating the severity of liver disease and could influence
treatment outcomes. It is recommended that you include this information to better contextualize
your findings.
Propensity-Matched Trial Considerations: One of the studies included in the analysis is based
on a propensity-matched trial. Please discuss potential confounders inherent in such a study
design, as these could affect the overall results of the meta-analysis. An exploration of how these
confounders might skew the findings will strengthen the validity of your conclusions.
Search Strategy Details: The search strategy would benefit from the inclusion of the date and
time of the searches performed. This information is essential for reproducibility and provides
important context regarding the literature coverage.
PROSPERO Registration: The manuscript does not indicate whether the review protocol
was registered on PROSPERO. Given the importance of protocol registration in ensuring
transparency and reducing reporting bias, please provide details regarding PROSPERO
registration, or explain why registration was not pursued.
I kindly request that you review and revise the manuscript to address these concerns.
Incorporating these points will significantly enhance the methodological transparency and
overall rigor of your study.
Sincerely,
Please review this paper.
user
Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 4 Date: 13 Mar 2025
Reviewer:  Avinash Tiwari
Reviewer's report:
Dear Authors,
I appreciated the opportunity to review your systematic review and meta-analysis titled
“Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis.” While your work is
informative and contributes valuable insights to the field, I have several concerns that should be
addressed to enhance the quality of the manuscript:
Liver Biopsy and Modified Histological Activity Index (mHAI): The manuscript does not
provide information regarding liver biopsy findings or the use of the modified histological
activity index (mHAI). Given that, in autoimmune hepatitis (AIH), clinical remission typically
precedes biochemical and histological remission—and that histological remission is often
assessed via mHAI—it is recommended that you discuss this aspect. Incorporating mHAI data is
vital, as many patients who achieve biochemical remission may still exhibit histological disease
activity, a fact emphasized in current guidelines.
Cost-Benefit Analysis: Although it is acknowledged that mycophenolate mofetil (MMF) is
associated with fewer side effects compared to azathioprine (AZA), the economic implications
of long-term immunosuppressive therapy are also crucial. A cost-benefit analysis would offer
important insights into the overall feasibility and affordability of MMF as a first-line treatment
option in clinical practice.
CTP/MELD Scores: There is a lack of information regarding the Child-Turcotte-Pugh (CTP)
and Model for End-Stage Liver Disease (MELD) scores of the patients included in the analysis.
These scores are essential for evaluating the severity of liver disease and could influence
treatment outcomes. It is recommended that you include this information to better contextualize
your findings.
Propensity-Matched Trial Considerations: One of the studies included in the analysis is based
on a propensity-matched trial. Please discuss potential confounders inherent in such a study
design, as these could affect the overall results of the meta-analysis. An exploration of how these
confounders might skew the findings will strengthen the validity of your conclusions.
Search Strategy Details: The search strategy would benefit from the inclusion of the date and
time of the searches performed. This information is essential for reproducibility and provides
important context regarding the literature coverage.
PROSPERO Registration: The manuscript does not indicate whether the review protocol
was registered on PROSPERO. Given the importance of protocol registration in ensuring
transparency and reducing reporting bias, please provide details regarding PROSPERO
registration, or explain why registration was not pursued.
I kindly request that you review and revise the manuscript to address these concerns.
Incorporating these points will significantly enhance the methodological transparency and
overall rigor of your study.
Sincerely,
assistant