Meta-Analysis
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2020; 26(38): 5896-5910
Published online Oct 14, 2020. doi: 10.3748/wjg.v26.i38.5896
Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?
Mohammadreza Abdollahi, Neda Khalilian Ekrami, Morteza Ghojazadeh, H Marike Boezen, Mohammadhossein Somi, Behrooz Z Alizadeh
Mohammadreza Abdollahi, Neda Khalilian Ekrami, H Marike Boezen, Behrooz Z Alizadeh, Department of Epidemiology, University of Groningen, Groningen 9700 RB, Netherlands
Morteza Ghojazadeh, Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
Mohammadhossein Somi, Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
Author contributions: Abdollahi M contributed to acquisition of data, analysis and interpretation of data, drafting the article, final approval; Khalilian Ekrami N contributed to acquisition of data, analysis and interpretation of data, drafting the article, final approval; Ghojazadeh M contributed to interpretation of data, revising the article, final approval; Boezen HM contributed to critical revision, final approval; Somi M and Alizadeh BZ contributed to conception and design of the study, critical revision, final approval.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammadreza Abdollahi, MD, PhD, Doctor, Department of Epidemiology, University of Groningen, Hanzeplein1, Groningen 9700 RB, Netherlands. m.abdollahi@umcg.nl
Received: May 28, 2020
Peer-review started: May 28, 2020
First decision: August 9, 2020
Revised: August 11, 2020
Accepted: September 17, 2020
Article in press: September 17, 2020
Published online: October 14, 2020
Abstract
BACKGROUND

The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce.

AIM

To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).

METHODS

A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI).

RESULTS

The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.

CONCLUSION

Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement.

Keywords: Autoimmune hepatitis, Efficacy, Grading of Recommendations Assessment, Development and Evaluation approach, Systematic review, Meta-analysis, Second-line

Core Tip: There is no consensus in the literature on which second-line treatment is superior in autoimmune hepatitis (AIH). This is the first systematic review and meta-analysis to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as second-line treatments in AIH. We also evaluated the quality of evidence for adding to the clinical guidelines for routine practice. We conclude that tacrolimus and MMF are considered effective for patients who are non-responders or intolerant to first-line treatment, but the quality of evidence is not high and it is questionable if these results should be added to clinical guidelines for AIH.