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Peer-Review Record

Ileal Bile Acid Transporter Blockers for Cholestatic Liver Disease in Pediatric Patients with Alagille Syndrome: A Systematic Review and Meta-Analysis

J. Clin. Med. 2022, 11(24), 7526; https://doi.org/10.3390/jcm11247526

by Hafiza Sidra tul Muntaha¹, Mubashar Munir², Syeda Haleema Sajid¹, Zouina Sarfraz³

, Azza Sarfraz^4,*, Karla Robles-Velasco⁵

, Muzna Sarfraz², Miguel Felix⁶

and Ivan Cherrez-Ojeda^5,*

Reviewer 1: Anonymous

Reviewer 2:

Marcos Brioschi

J. Clin. Med. 2022, 11(24), 7526; https://doi.org/10.3390/jcm11247526

Submission received: 27 November 2022 / Revised: 13 December 2022 / Accepted: 14 December 2022 / Published: 19 December 2022

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

Round 1

Reviewer 1 Report

Main Comments:

(1) This manuscript deals with the efficacy of ileal bile acid transporter blockers for cholestatic liver disease in pediatric patients with Alagille Syndrome. It offers a systematic review and a meta-analysis. Although it is limited by the data available in the literature and the most efficacious dosage regimen could not be ascertained, it provides an overview on the current state of research as well as some recommendations.

(2) "embrytoxon" (line 39) -> the correct term is embryotoxon.

(3) "pruritis" (line 45, lines 48/49, and many other times throughout the text) -> the correct term is pruritus.

(4) Table 1: The relationship between study No. 1 and study No. 2 should be explained in a footnote, so that readers can understand the tenth column of the table ("Interventions") independently from the rest of the article.

Additional Comments/Suggestions:

(5) The page numbers (in the top right corner of the pages) are not correct; e.g., "2 out of 21" is used four times.

(6) Line 65: "adhered to adhering to…" -> adhered to…

(7) Line 84: "spreadsheet. the third reviewer…" -> spreadsheet. The third reviewer…

(8) Line 172: "Schneider et al." -> Shneider et al.

(9) Line 340-342: "Both different measures of ItchRO, including patient- and observer-rated, is designed for patients aged 9 years older and caregiver of those who are younger, respectively" – please improve this sentence.

(10) Lines 364/365: "Maralixibat, an IBAT" -> Maralixibat, an IBAT Inhibitor.

(11) Figure legend 9: "Ileal bile acid transporter blockers (IBAT)" -> Ileal bile acid transporter (IBAT) blockers.

(12) Lines 392-396: "However, IBAT treatment was associated with elevations in ALT levels which may be a treatment effect. It remains of interest whether different IBAT dosing regimens may improve the sBAs and pruritis severity without causing drug-induced hepatotoxicity [37] such that the benefits of IBAT may be retained without compromising liver function integrity in AGLS patients" -> However, treatment with IBAT inhibitors was associated with elevations in ALT levels which may be a treatment effect. It remains of interest whether different IBAT inhibitor dosing regimens may improve the sBAs and pruritus severity without causing drug-induced hepatotoxicity [37] such that the benefits of IBAT inhibitors may be retained without compromising liver function integrity in AGLS patients.

(13) Line 429: "ABAT blockers" -> IBAT blockers.

(14) Please improve Reference 30.

Author Response

Reviewer 1 Comments and Responses:

Main Comments:

Comment 1: This manuscript deals with the efficacy of ileal bile acid transporter blockers for cholestatic liver disease in pediatric patients with Alagille Syndrome. It offers a systematic review and a meta-analysis. Although it is limited by the data available in the literature and the most efficacious dosage regimen could not be ascertained, it provides an overview on the current state of research as well as some recommendations.

Response to reviewer comment: Thank you for your analysis. It is greatly appreciated.

Comment 2: "embrytoxon" (line 39) -> the correct term is embryotoxon.

Response to reviewer comment: Thank you for noting the discrepancy. It has been updated.

Comment 3: "pruritis" (line 45, lines 48/49, and many other times throughout the text) -> the correct term is pruritus.

Response to reviewer comment: Thank you for noting the discrepancy. It has been updated word by word throughout the manuscript. It is highlighted in yellow.

Comment 4: Table 1: The relationship between study No. 1 and study No. 2 should be explained in a footnote, so that readers can understand the tenth column of the table ("Interventions") independently from the rest of the article.

Response to reviewer comment: That is indeed a very helpful comment. Please note that I have made updates to the table’s footnote with the following:

“*It must be noted that both studies by Gonzales and Kamath stem from a same primary clinical trial: “Safety and Efficacy Study of LUM001 (Mara-lixibat) With a Drug Withdrawal Period in Participants With Alagille Syndrome (ALGS) (ICONIC)” with a NCT number of (NCT02160782).”

Additional Comments/Suggestions:

Comment 5: The page numbers (in the top right corner of the pages) are not correct; e.g., "2 out of 21" is used four times.

Response to reviewer comment: All page numbers appear in their correct order now. Your are requested to have a look. Thank you very much for noting the discrepancy.

Comment 6: Line 65: "adhered to adhering to…" -> adhered to…