Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review

BACKGROUND 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. AIM To systematically review the early treatment efficacy of AdoMet in adult patients with IHC. METHODS 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 (gamma GT) 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. RESULTS 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 gamma GT 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 gamma GT 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. CONCLUSION 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.