Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. [Parenteral S-adenosylmethionine compared to placebos in the treatment of alcoholic liver diseases].
S-Adenosyl-L-methionine (SAMe) is a physiologic precursor of thiols and sulfurated compounds, which are known to be decreased in patients with liver disease. The effect of its administration on the hepatic glutathione content of liver patients was investigated. Four groups of subjects were selected: a) 9 patients with alcoholic liver disease treated with SAMe (1.2 g/day orally for 6 months); b) 7 patients with non-alcoholic liver disease treated as above; c) 8 placebo-treated patients with alcoholic liver disease; and d) 15 normal subjects as a control group. Total and oxidized glutathione were assayed by high-performance liquid chromatography of liver biopsy specimens before and after the treatment period. In all patients pre-treatment hepatic glutathione was significantly decreased as compared with controls. SAMe therapy resulted in a significant increase of hepatic glutathione levels both in patients with alcoholic and in those with non-alcoholic liver diseases as compared with placebo-treated patients. SAMe may therefore exert an important role in reversing hepatic glutathione depletion in patients with liver disease. The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis.
                A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg/day, orally) or placebo for 2 years. All patients had alcoholic cirrhosis, and histologic confirmation of the diagnosis was available in 84% of the cases. Seventy-five patients were in Child class A, 40 in class B, and 8 in class C. Sixty-two patients received AdoMet and 61 received placebo.
                At inclusion into the trial no significant differences were observed between the two groups with respect to sex, age, previous episodes of major complications of cirrhosis, Child classification and liver function tests. The overall mortality/liver transplantation at the end of the trial decreased from 30% in the placebo group to 16% in the AdoMet group, although the difference was not statistically significant (p = 0.077). When patients in Child C class were excluded from the analysis, the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group (29% vs. 12%, p = 0.025), and differences between the two groups in the 2-year survival curves (defined as the time to death or liver transplantation) were also statistically significant (p = 0.046).
                The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis, especially in those with less advanced liver disease. We measured glutathione and cysteine concentrations in erythrocytes of chronic alcohol misusers with (20 subjects) and without liver cirrhosis (20 subjects). Glutathione levels were decreased, whereas those of cysteine were increased in all patients. Parenteral treatment with S-adenosylmethionine (SAME); (2 g daily in 250 ml 0.15 M NaCl for 15 days) corrected the erythrocyte thiol alterations. We conclude that parenteral treatment with SAME affects the metabolism of SH compounds in erythrocytes of alcoholic patients. The improvements in the knowledge of the action of ethanol over the hepatic cell, its direct action over the cell, and the intracytoplasmatic structures membranes, point out the possibilities of use of sulfo-adenosil-L-metionina (SAMe); as an util drug inn the treatment of the altered metilation reactions, that take place in those membranes, facilitating their physiological functions. The primary end point in this study was to demonstrate the therapeutic worth os SAMe, by parenteral route in 45 patients with alcoholic liver disease, which were determined by clinical laboratory and hepatic function test, label qith 32 points or more of the discriminatory function index. Divided into two groups, placebo-SAMe, randomized, double blind. As well as total plasmatic and reduced glutation and lipoperoxidation index, indirect form as malondehaldehyde. Were determined at the first visit anf after 8 and 15 days of treatment. Comparing the results of both groups there were a significative favorable results for the group treatment with SAMe and this confirms the utility of this drug in the treatment of patients with alcoholic liver disease with a discriminatory function index (Maddrey index), of 32 points or more.
We could not find evidence supporting or refuting the use of SAMe for patients with alcoholic liver diseases. We need more long-term, high-quality randomised trials on SAMe for these patients before SAMe may be recommended for clinical practice.