S-Adenosylmethionine in the treatment of intrahepatic cholestasis of chronic liver disease: A field trial

In a controlled, open-label trial, 640 patients with intrahepatic cholestasis (IHC) complicating chronic liver disease (cirrhosis, 309 patients; chronic viral hepatitis, 190; primary biliary cirrhosis, 16; and primary sclerosing cholangitis, 14) received S-adenosylmethionine (SAMe) (1,4 butandisulfonate salt) in 1 of 2 dosing regimens: SAMe 500 mg once daily intramuscularly (IM) or SAMe 800 mg/d intravenously (IV). Patients with acute hepatitis, hepatic tumors, extrahepatic biliary obstruction, skin disease, and current alcohol intake >60 g/d were excluded from the study. Intrahepatic cholestasis was defined as an increase in serum total bilirubin (STB), serum conjugated bilirubin (SCB) concentrations at least twice the normal level and an increase in serum alkaline phosphatase (ALP) activity above normal values. Safety, efficacy, and tolerability were assessed after 7 and 15 days of treatment. The indicators of efficacy were improvement or disappearance of pruritus and fatigue and improvements in the results of liver function studies (normalization or a 50% reduction in STB or SCB, and normalization or a 30% reduction in ALP at the end of treatment). The efficacy and safety of SAMe were assessed as an intent-to-treat design. After 7 days of treatment, biochemical response was found in 39% and 43% of patients treated with SAMe 500 mg IM and SAMe 800 mg IV, respectively. At the end of treatment, the biochemical response was 61% with SAMe 500 mg IM and 62% with SAMe 800 mg IV. Pruritus improved or disappeared in 74% of patients treated with SAMe 500 mg IM and in 69% of those treated with SAMe 800 mg IV. Improvement or disappearance of fatigue occurred in 72% with SAMe 500 mg IM and in 69% with SAMe 800 mg IM. Fifteen patients (2.3%) discontinued treatment prematurely. Both dose regimens were well tolerated and were associated with a low incidence of adverse effects (2.6% in the SAMe IM and 1.9% in the SAMe IV treatment group). Results of the present study suggest that both parenteral dose regimens of SAMe were well tolerated and effective in the short-term treatment of IHC in patients with chronic liver disease.