Prior studies in animal models have established that the pathogenesis of alcoholic liver
disease (ALD) is regulated in part by the effects of chronic alcohol abuse on hepatic
methionine metabolism. The hypothesis of the clinical study was that provision of the
methionine metabolite S-adenosylmethionine (SAM) would correct abnormal hepatic methionine
metabolism thereby effectively treating ALD. The two goals of the clinical research were
a)to determine the clinical relationship of aberrant hepatic methionine metabolism to ALD by
comparisons of patterns of serum methionine metabolites in groups of ALD patients,
alcoholics without liver disease, and normal healthy subjects, and b) to determine the
treatment effects of SAM on patterns of serum methionine metabolites and on the
histopathology and biochemical features of liver injury in ALD patients.
We assessed a total of 297 potential ALD candidates, from whom 40 were enrolled in the
study. In addition, we enrolled 26 gender matched active alcohol drinkers without liver
disease (AD) and 28 age and gender matched healthy control subjects (HS). Of the original 40
ALD subjects who provided initial enrollment data, 3 declined to proceed with the trial.
Therefore, 37 ALD patients were randomized to receive SAM at a dose of 400 mg or placebo
three times daily for 24 weeks. However 11 of these dropped out after initial evaluation,
leaving 26 ALD patients, 13 in each arm, who completed the 24 week trial.
- ALD) a history of chronic alcoholism according to established AUDIT and WHO criteria
with the presence of clinical and laboratory features of established liver disease.
Also, willingness to undergo liver biopsies at start and completion of the study, and
to comply with study medication or placebo and required clinic visits and blood
- a history of chronic alcoholism without evidence of liver disease;
- healthy subjects without history of alcoholism or presence of liver disease.
- viral Hepatitis B or C
- Wilson Disease
- sclerosing cholangitis
- primary biliary cirrhosis
- other chronic disease
- renal insufficiency