Title: The Role of Seladelpar in Primary Biliary Cholangitis: A Systematic Review and Meta-
Analysis
Version: 0 Date: 07 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although non-English studies were excluded, including them could enhance the
comprehensiveness of the review. If language bias is a concern, the authors could consider
including a method for handling studies in different languages (e.g., translation or summarizing
results).
-It’s great that grey literature sources were searched, but more details about how this was
done (e.g., specific databases or platforms) would be useful. Additionally, the authors should
comment on any challenges faced in identifying or evaluating grey literature.
-The inclusion of various adverse events, such as pruritus and abdominal pain, is a strong point.
However, a more detailed breakdown of the severity and frequency of these events, along with
their impact on treatment adherence, could further enrich the analysis.
-Although the authors mention heterogeneity across studies, the discussion could provide more
details on the potential causes of the heterogeneity. For example, it would be helpful to delve
deeper into the specific dosages and disease severities in the studies included, as these factors
may influence outcomes significantly. Additionally, more specific data on the random-effects
model and its implications could further support the analysis.
-While the long-term safety concerns of Seladelpar are mentioned, it would be useful to provide
a more detailed examination of these issues. For instance, what were the specific adverse events
that occurred after long-term usage? How do these compare to other treatments over an extended
period? This would help in weighing the risk-benefit profile of Seladelpar for chronic use.
-The absence of immunohistochemistry evaluation in the included studies is a limitation that
could be more thoroughly addressed. Understanding Seladelpar’s mechanistic effects on the
liver, such as its anti-fibrotic and anti-inflammatory properties, would significantly enhance the
understanding of its potential benefits. Providing suggestions for how future studies could better
explore these mechanisms would be helpful.
-The discussion briefly touches on adverse effects such as abdominal pain, headache, and
gastrointestinal upset. However, more details about the severity of these side effects, their
impact on treatment adherence, and how Seladelpar compares with other treatments in terms
of tolerability would add depth to the safety analysis. Additionally, the impact of comorbidities
(e.g., cardiovascular conditions) on Seladelpar's safety profile could be explored further.
-The authors mention comparing Seladelpar with other emerging medications, but this
comparison could be more detailed. How does Seladelpar compare with other PPAR agonists
or novel treatments for PBC in terms of efficacy, safety, and long-term benefits?
Title: The Role of Seladelpar in Primary Biliary Cholangitis: A Systematic Review and Meta-
Analysis
Version: 0 Date: 07 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although non-English studies were excluded, including them could enhance the
comprehensiveness of the review. If language bias is a concern, the authors could consider
including a method for handling studies in different languages (e.g., translation or summarizing
results).
-It’s great that grey literature sources were searched, but more details about how this was
done (e.g., specific databases or platforms) would be useful. Additionally, the authors should
comment on any challenges faced in identifying or evaluating grey literature.
-The inclusion of various adverse events, such as pruritus and abdominal pain, is a strong point.
However, a more detailed breakdown of the severity and frequency of these events, along with
their impact on treatment adherence, could further enrich the analysis.
-Although the authors mention heterogeneity across studies, the discussion could provide more
details on the potential causes of the heterogeneity. For example, it would be helpful to delve
deeper into the specific dosages and disease severities in the studies included, as these factors
may influence outcomes significantly. Additionally, more specific data on the random-effects
model and its implications could further support the analysis.
-While the long-term safety concerns of Seladelpar are mentioned, it would be useful to provide
a more detailed examination of these issues. For instance, what were the specific adverse events
that occurred after long-term usage? How do these compare to other treatments over an extended
period? This would help in weighing the risk-benefit profile of Seladelpar for chronic use.
-The absence of immunohistochemistry evaluation in the included studies is a limitation that
could be more thoroughly addressed. Understanding Seladelpar’s mechanistic effects on the
liver, such as its anti-fibrotic and anti-inflammatory properties, would significantly enhance the
understanding of its potential benefits. Providing suggestions for how future studies could better
explore these mechanisms would be helpful.
-The discussion briefly touches on adverse effects such as abdominal pain, headache, and
gastrointestinal upset. However, more details about the severity of these side effects, their
impact on treatment adherence, and how Seladelpar compares with other treatments in terms
of tolerability would add depth to the safety analysis. Additionally, the impact of comorbidities
(e.g., cardiovascular conditions) on Seladelpar's safety profile could be explored further.
-The authors mention comparing Seladelpar with other emerging medications, but this
comparison could be more detailed. How does Seladelpar compare with other PPAR agonists
or novel treatments for PBC in terms of efficacy, safety, and long-term benefits?
Please review this paper.
user
Title: The Role of Seladelpar in Primary Biliary Cholangitis: A Systematic Review and Meta-
Analysis
Version: 0 Date: 07 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although non-English studies were excluded, including them could enhance the
comprehensiveness of the review. If language bias is a concern, the authors could consider
including a method for handling studies in different languages (e.g., translation or summarizing
results).
-It’s great that grey literature sources were searched, but more details about how this was
done (e.g., specific databases or platforms) would be useful. Additionally, the authors should
comment on any challenges faced in identifying or evaluating grey literature.
-The inclusion of various adverse events, such as pruritus and abdominal pain, is a strong point.
However, a more detailed breakdown of the severity and frequency of these events, along with
their impact on treatment adherence, could further enrich the analysis.
-Although the authors mention heterogeneity across studies, the discussion could provide more
details on the potential causes of the heterogeneity. For example, it would be helpful to delve
deeper into the specific dosages and disease severities in the studies included, as these factors
may influence outcomes significantly. Additionally, more specific data on the random-effects
model and its implications could further support the analysis.
-While the long-term safety concerns of Seladelpar are mentioned, it would be useful to provide
a more detailed examination of these issues. For instance, what were the specific adverse events
that occurred after long-term usage? How do these compare to other treatments over an extended
period? This would help in weighing the risk-benefit profile of Seladelpar for chronic use.
-The absence of immunohistochemistry evaluation in the included studies is a limitation that
could be more thoroughly addressed. Understanding Seladelpar’s mechanistic effects on the
liver, such as its anti-fibrotic and anti-inflammatory properties, would significantly enhance the
understanding of its potential benefits. Providing suggestions for how future studies could better
explore these mechanisms would be helpful.
-The discussion briefly touches on adverse effects such as abdominal pain, headache, and
gastrointestinal upset. However, more details about the severity of these side effects, their
impact on treatment adherence, and how Seladelpar compares with other treatments in terms
of tolerability would add depth to the safety analysis. Additionally, the impact of comorbidities
(e.g., cardiovascular conditions) on Seladelpar's safety profile could be explored further.
-The authors mention comparing Seladelpar with other emerging medications, but this
comparison could be more detailed. How does Seladelpar compare with other PPAR agonists
or novel treatments for PBC in terms of efficacy, safety, and long-term benefits?
assistant