Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2020; 12(2): 46-63
Published online Feb 27, 2020. doi: 10.4254/wjh.v12.i2.46
Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review
Mazen Noureddin, Suntje Sander-Struckmeier, José M Mato
Mazen Noureddin, Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Suntje Sander-Struckmeier, Gastroenterology/Hepatology, Abbott Laboratories GmbH, Hannover 30173, Germany
José M Mato, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, Derio 48160, Bizkaia, Spain
Author contributions: All authors contributed to the conception and development of the paper, approved the final version, and agree to be accountable for all aspects of the work.
Conflict-of-interest statement: Noureddin M has been on the advisory board or a speaker for Allergan, Gilead, Intercept, Pfizer, Novartis, Blade, EchoSens North America, OWL, Simply Speaking, and Abbott. He has also received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire, and Zydus. He is a minor shareholder in Anaetos and Viking. Sander-Struckmeier S is an employee of Abbott. Mato JM has served on advisory boards for Abbott, Galmed, and OWL Metabolomics, and is a shareholder of OWL Metabolomics.
PRISMA 2009 Checklist statement: 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:
Corresponding author: José M Mato, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, Parque Tecnológico de Bizkaia, Derio 48160, Bizkaia, Spain.
Received: September 11, 2019
Peer-review started: September 11, 2019
First decision: November 2, 2019
Revised: December 4, 2019
Accepted: December 13, 2019
Article in press: December 13, 2019
Published online: February 27, 2020
Research background

Intrahepatic cholestasis (IHC) is a key feature of several chronic liver diseases and is associated with clinical signs and symptoms such as pruritus, jaundice, and fatigue, which may subsequently be associated with depression, autonomic dysfunction, and sleep disturbances. S-adenosylmethionine (AdoMet) is a metabolically pleiotropic molecule that is used to treat IHC.

Research motivation

The efficacy of AdoMet has been demonstrated by several clinical studies and a previous systematic review and meta-analysis; however, the efficacy of AdoMet in the early weeks of treatment has not been systematically investigated.

Research objectives

The primary objective of this systematic review was to evaluate the efficacy of AdoMet in improving biochemical liver parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT)] in adult patients with IHC within 8 wk of initiating treatment. The secondary objective was to assess the efficacy of AdoMet in improving the clinical symptoms of cholestasis within this timeframe.

Research methods

Published clinical trials reporting the efficacy of AdoMet (intravenous, intramuscular, or oral forms) within 8 wk of treatment initiation in adult patients with IHC were considered for inclusion in the review. Mean serum levels of ALT, AST, ALP, and γGT following AdoMet treatment vs placebo, comparator, or baseline were summarized. Changes in patient-reported clinical symptoms of cholestasis (such as fatigue and depression) were also reviewed.

Research results

In total, three randomized and six non-randomized (observational) studies of patients with IHC were included in the systematic review. Of the three randomized studies, two were double-blind and placebo-controlled, and one was comparator-controlled with unclear blinding and a relatively high risk of bias. Both of the double-blind placebo-controlled randomized studies and all of the non-randomized studies (4/4) that investigated changes in ALT, AST, ALP, and/or γGT within 2 wk of AdoMet treatment initiation reported significant reductions in at least two of these parameters. Reductions in patient-reported fatigue and depression were also reported within 2 wk in some studies.

Research conclusions

Clinical data from the randomized and non-randomized studies included in this systematic review suggest that AdoMet shows clinical efficacy within the first 2 wk of treatment, as some studies reported reductions in liver enzymes and improvements in clinical symptoms of cholestasis within this short timeframe.

Research perspectives

Sustained treatment efficacy is crucial in patients with IHC, but the early onset of efficacy may also be a key consideration to facilitate rapid improvements in liver function, leading to a prompt reduction in the distressing symptoms of cholestasis. In terms of future research, further targeted clinical studies are desired to determine the speed of onset of the clinical impact of AdoMet in patients with specific liver diseases.