Published online Feb 27, 2020. doi: 10.4254/wjh.v12.i2.46
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
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.
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.
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.
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.
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.
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.
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.