MULTICENTER DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF INTRAVENOUS AND ORAL S-ADENOSYL-L-METHIONINE (SAME) IN CHOLESTATIC PATIENTS WITH LIVER-DISEASE

A multicentre double-blind placebo-controlled trial of 2 weeks' therapy with either intravenous S-adenosyl-L-methionine (SAMe) 800 mg/day or placebo in 343 patients with-intrahepatic cholestasis due to acute hepatitis or chronic liver disease was conducted to investigate the anticholestatic effect of SAMe. Patients with chronic liver disease who responded to intravenous SAMe (50% decrease or normalisation of serum total or conjugated bilirubin, or alkaline phosphatase) were subsequently randomly allocated to receive either oral SAMe 1600 mg/day or placebo for 8 weeks. In chronic liver disease intravenous SAMe was significantly (p < 0.05) more effective than placebo in improving levels of serum total and conjugated bilirubin, aminotransferases and gamma-glutamyl transferase, whereas alkaline phosphatase levels were not significantly changed in either group. SAMe treatment was significantly more effective than placebo in resolving pruritus (p < 0.001). Intravenous SAMe induced a significantly (p < 0.01) greater improvement than placebo with respect to all considered biochemical parameters in acute hepatitis. Pruritus was totally relieved by SAMe, whereas placebo had no effect (p < 0.001). 60% of patients with chronic liver disease were considered to be responders to intravenous SAMe, whereas 34% responded to placebo administration (p < 0.001; odds ratio 2.9; 95% confidence intervals of 1.7 to 4.8). 68 of the patients who responded to intravenous SAMe entered the oral phase of the study. A further significant decrease (p < 0.01) in serum total and conjugated bilirubin and alkaline phosphatase concentrations was observed at the end of treatment with oral SAMe, whereas values in the placebo group were significantly increased (p < 0.01). The serum levels of these markers of intrahepatic cholestasis observed at the end of oral treatment with SAMe or placebo did not correlate with the previous response to intravenous SAMe. Continuation with oral SAMe treatment is advisable as it not only maintains or improves the effects achieved during intravenous therapy, but also may induce a response in patients who did not improve after intravenous treatment. Intravenous and oral SAMe was as well tolerated as placebo.