S-adenosyl-L-methionine for alcoholic liver diseases.
BACKGROUND
Alcohol is a major cause of liver disease in the Western world today. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for all known biological methylation reactions and participates in the synthesis of glutathione, the main cellular anti-oxidant. Randomised clinical trials have addressed the question whether SAMe has any efficacy in patients with alcoholic liver diseases.


OBJECTIVE
The objectives were to assess the efficacy of SAMe on mortality, clinical symptoms, complications, liver biochemistry, and liver histology in patients with alcoholic liver diseases. Adverse events were also analysed.


METHODS
The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and full text searches were combined.


METHODS
Randomised clinical trials studying patients with alcoholic liver diseases were included. Interventions encompassed peroral or parenteral administration of SAMe at any dose versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published as an article, an abstract, or a letter, and no language limitations were applied.


METHODS
All analyses were performed according to the intention-to-treat method. The statistical package (RevMan and MetaView) provided by the Cochrane Collaboration was used. The methodological quality of the randomised clinical trials was evaluated by components of quality and the Jadad-score.


RESULTS
Eight placebo-controlled randomised clinical trials including a heterogeneous sample of 330 patients with alcoholic liver disease were identified. Only one trial including 123 patients with alcoholic cirrhosis used adequate methodology and reported clearly on mortality and liver transplantation. It demonstrated no significant effects of SAMe on mortality (Peto odds ratio (OR) 0.53, 95% confidence interval (CI) 0.22 to 1.29), liver related mortality (OR 0.63, 95% CI 0.25 to 1.58), mortality or liver transplantation (OR 0.47; 95% CI 0.20 to 1.09), or patients without complications (OR 0.63, 95% CI 0.30 to 1.31). SAMe was not significantly associated with adverse events (OR 3.95, 95% CI 0.77 to 20.24).


CONCLUSIONS
This systematic review could not demonstrate any significant effect of SAMe on mortality, liver related mortality, mortality or liver transplantation, and liver complications of patients with alcoholic liver disease. SAMe should not be used for alcoholic liver disease outside randomised clinical trials.
Rambaldi
A
A
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshopitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. arambaldi@hotmail.com
Gluud
C
C
D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012436:S-Adenosylmethionine / Q000627:therapeutic use*
D012436:S-Adenosylmethionine