S-Adenosyl-L-Methionine for the Treatment of Chronic Liver Disease: A Systematic Review and Meta-Analysis

Abstract

It has been well established that S-adenosyl-L-methionine (SAMe) is the principal methyl donor in methyltransferase reactions and that SAMe supplementation restores hepatic glutathione (GSH) deposits and attenuates liver injury. However, the effectiveness of SAMe therapy in chronic liver disease has not been adequately addressed. We searched globally recognized electronic databases, including PubMed, the Cochrane Database and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of chronic liver disease published in the past 20 years. We then performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria.The results showed that twelve RCTs from 11 studies, which examined 705 patients, were included in this research. For liver function, certain results obtained from data synthesis and independent comparisons demonstrated significant differences between the levels of total bilirubin (TBIL) and aspartate transaminase (AST). However, no studies identified significant differences regarding alanine transaminase (ALT) levels. An analysis of the adverse events and long-term prognosis also indicated no significant differences between the SAMe and the placebo groups. In a subgroup analysis of gravidas and children, several of the included data indicated that there was a significant difference in the pruritus score. Furthermore, the results regarding ursodeoxycholic acid (UDCA) and stronger neo-minophagen C (SNMC) indicated that both treatments were more effective than SAMe was in certain chronic liver diseases. These findings suggest that SAMe could be used as the basis of a medication regimen for liver function improvement because of its safety. However, SAMe also demonstrated limited clinical value in the treatment of certain chronic liver diseases.

Feasibility and Efficacy of S-Adenosyl-L-methionine in Patients with HBV-Related HCC with Different BCLC Stages

“…SAMe has been used for the treatment of chronic liver disease for decades. Our previous meta-analysis confirmed the protective effects and safety of SAMe for chronic liver disease [22]. Animal experiments have indicated that intrahepatic SAMe depletion is associated with hepatic fibrosis [23].…”

GADD45β induction by S-adenosylmethionine inhibits hepatocellular carcinoma cell proliferation during acute ischemia-hypoxia

“…Most patients with liver injury or a chronic liver disease, like cirrhosis, have impaired SAMe biosynthesis due to reduced MAT1A expression and MAT I/III inactivation, which are respectively the enzyme and isoenzyme involved in SAMe synthesis in normal hepatocytes [11, 12]. SAMe may inhibit tumor growth, reduce tumor invasiveness and slow metastasis through methyl group donation leading to gene hypermethylation and reduction of overall hypomethylation to inhibit oncogene expression [13–15].…”

Essential roles of bile acids and their nuclear receptors, FXR and PXR, in the cholestatic liver disease

“…For the treatment of cholestatic liver diseases, treatment with ursodeoxycholic acid (UDCA) has been clinically approved to slow the progression of chronic cholangiopathies, but still has limitations to various chronic cholestatic liver diseases. UDCA, the only drug approved by Food and Drug Administration for the treatment of primary bilary cirrhosis, has antioxidant properties (Poupon et al 1987;Pares et al 2000;Guo et al 2015). UDCA can scavenge hydroxyl radicals and induce gene expressions involved in antioxidant defenses, including glutathione (GSH) synthesis (Guo et al 2015).…”

“…UDCA, the only drug approved by Food and Drug Administration for the treatment of primary bilary cirrhosis, has antioxidant properties (Poupon et al 1987;Pares et al 2000;Guo et al 2015). UDCA can scavenge hydroxyl radicals and induce gene expressions involved in antioxidant defenses, including glutathione (GSH) synthesis (Guo et al 2015). However, the efficacy of UDCA is limited to the early stages PBC, novel therapeutic strategies for the treatment of cholestatic liver diseases are required to be developed.…”