Title: Efficacy and Safety of PPAR agonists in Primary Biliary Cholangitis: A Systematic
Review and Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 10 Feb 2025
Reviewer's report:
The manuscript by Saeedian et al. presents a systematic review and meta-analysis evaluating the
efficacy and safety of PPAR agonists in patients with PBC. The study aims to determine whether
PPAR agonists, when used in combination with UDCA, can improve biochemical markers and
clinical outcomes in PBC patients who do not adequately respond to UDCA alone. However,
the following issues should be addressed before it can be considered for publication.
1. The study reports significant heterogeneity in the meta-analysis for several outcomes,
including ALP (I² = 82%), GGT (I² = 92%), and total bilirubin (I² = 53%). The authors have
conducted sensitivity analyses and subgroup analyses, but the high heterogeneity suggests
potential variability in study populations, interventions, and outcomes that need to be addressed
more thoroughly.
2. Funnel plots and Egger's tests suggest the presence of publication bias for GGT and total
bilirubin levels. The authors should provide a more detailed discussion on the potential sources
of bias and how they might have affected the results.
3. Some studies included in the meta-analysis had missing data for certain outcomes (e.g., ALT,
AST, pruritus). The authors should provide a more detailed explanation of how they addressed
these missing data and the potential impact on the overall findings.
4. The study includes both open-label and double-blind trials, which can introduce bias. The
authors should discuss the potential impact of this variability on the study outcomes and the
robustness of their findings.
5. The study should provide more detailed information on the safety profile of the different
PPAR agonists, including a summary of adverse events and serious adverse events.
Title: Efficacy and Safety of PPAR agonists in Primary Biliary Cholangitis: A Systematic
Review and Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 10 Feb 2025
Reviewer's report:
The manuscript by Saeedian et al. presents a systematic review and meta-analysis evaluating the
efficacy and safety of PPAR agonists in patients with PBC. The study aims to determine whether
PPAR agonists, when used in combination with UDCA, can improve biochemical markers and
clinical outcomes in PBC patients who do not adequately respond to UDCA alone. However,
the following issues should be addressed before it can be considered for publication.
1. The study reports significant heterogeneity in the meta-analysis for several outcomes,
including ALP (I² = 82%), GGT (I² = 92%), and total bilirubin (I² = 53%). The authors have
conducted sensitivity analyses and subgroup analyses, but the high heterogeneity suggests
potential variability in study populations, interventions, and outcomes that need to be addressed
more thoroughly.
2. Funnel plots and Egger's tests suggest the presence of publication bias for GGT and total
bilirubin levels. The authors should provide a more detailed discussion on the potential sources
of bias and how they might have affected the results.
3. Some studies included in the meta-analysis had missing data for certain outcomes (e.g., ALT,
AST, pruritus). The authors should provide a more detailed explanation of how they addressed
these missing data and the potential impact on the overall findings.
4. The study includes both open-label and double-blind trials, which can introduce bias. The
authors should discuss the potential impact of this variability on the study outcomes and the
robustness of their findings.
5. The study should provide more detailed information on the safety profile of the different
PPAR agonists, including a summary of adverse events and serious adverse events.
Please review this paper.
user
Title: Efficacy and Safety of PPAR agonists in Primary Biliary Cholangitis: A Systematic
Review and Meta-Analysis of Randomized Controlled Trials
Version: 1 Date: 10 Feb 2025
Reviewer's report:
The manuscript by Saeedian et al. presents a systematic review and meta-analysis evaluating the
efficacy and safety of PPAR agonists in patients with PBC. The study aims to determine whether
PPAR agonists, when used in combination with UDCA, can improve biochemical markers and
clinical outcomes in PBC patients who do not adequately respond to UDCA alone. However,
the following issues should be addressed before it can be considered for publication.
1. The study reports significant heterogeneity in the meta-analysis for several outcomes,
including ALP (I² = 82%), GGT (I² = 92%), and total bilirubin (I² = 53%). The authors have
conducted sensitivity analyses and subgroup analyses, but the high heterogeneity suggests
potential variability in study populations, interventions, and outcomes that need to be addressed
more thoroughly.
2. Funnel plots and Egger's tests suggest the presence of publication bias for GGT and total
bilirubin levels. The authors should provide a more detailed discussion on the potential sources
of bias and how they might have affected the results.
3. Some studies included in the meta-analysis had missing data for certain outcomes (e.g., ALT,
AST, pruritus). The authors should provide a more detailed explanation of how they addressed
these missing data and the potential impact on the overall findings.
4. The study includes both open-label and double-blind trials, which can introduce bias. The
authors should discuss the potential impact of this variability on the study outcomes and the
robustness of their findings.
5. The study should provide more detailed information on the safety profile of the different
PPAR agonists, including a summary of adverse events and serious adverse events.
assistant