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

S-adenosylmethionine (AdoMet) is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis (IHC) and chronic liver diseases. While the efficacy of AdoMet has been demonstrated previously, it has not been systematically investigated within the early weeks of treatment.


To systematically review the early treatment efficacy of AdoMet in adult patients with IHC.


Studies reporting the efficacy of intravenous, intramuscular, or oral forms of AdoMet within 8 wk of treatment initiation were considered; three randomized and six non-randomized studies were eligible for inclusion (PROSPERO registration number CRD42018090936). 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. Mean serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) following AdoMet treatment vs placebo, comparator, or baseline were summarized to determine differences in liver enzymes. Changes in patient-reported clinical symptoms of cholestasis were also summarized.


Both placebo-controlled randomized studies reported significant reductions in serum ALT levels with AdoMet vs placebo within 2 wk. One of these also reported significant ALP reductions, and the other reported significant AST and γGT reductions within 2 wk. The comparator-controlled randomized study, which had a number of notable limitations, reported significant reductions in serum ALT and AST levels with AdoMet vs potassium magnesium aspartate within 4 wk, but not within2 wk. All of the non-randomized studies (4/4) that investigated ALT, AST, ALP and/or γGT reported significant reductions in at least two of these parameters within 2 wk. Of the five studies that evaluated fatigue, reductions were observed within 2 wk in one randomized and two non-randomized studies. The remaining two non-randomized studies reported improvements in fatigue within 6 and 8 wk. Of the four studies reporting symptoms of depression, two non-randomized studies observed improvements within 2 wk and the other two observed improvements within 17 d and 8 wk.


Data from both randomized and non-randomized studies suggest that AdoMet improves some biochemical liver parameters and symptoms of cholestasis within 2 wk, with further improvements observed in some studies after 4 and 8 wk of treatment.

Keywords: S-adenosylmethionine, Intrahepatic cholestasis, Chronic liver disease, Liver enzymes, Symptoms of cholestasis

Core tip: Chronic liver diseases are associated with substantial mortality and morbidity, and are a significant healthcare burden. Therapies that rapidly reverse or inhibit the deterioration of liver function in patients with intrahepatic cholestasis would therefore be beneficial. In this study, we provide new insight into the efficacy of S-adenosylmethionine in treating these patients, demonstrating that S-adenosylmethionine improves some biochemical liver parameters and symptoms of cholestasis within 2 wk, with further improvements observed in some studies after 4 and 8 wk of treatment.