1. S-Adenosyl-l-methionine is reported to improve serum liver function tests in chronic liver disease. Because liver disease is complicated by cholesterol deposition in hepatic and extrahepatic membranes, we have assessed whether oral administration of S-adenosyl-l-methionine to patients with hepatic disease can reverse the cholesterol enrichment of their erythrocytes.

2. The mean erythrocyte cholesterol-to-phospholipid molar ratio in 13 jaundiced patients was reduced 2 weeks after oral administration of S-adenosyl-l-methionine (from 0.874 ± 0.112 to 0.844 ± 0.102, P<0.05) with 10 of the patients (77%) showing a decrease. By contrast, only four of 11 untreated patients (36%) had a reduced erythrocyte cholesterol-to-phospholipid molar ratio after 2 weeks and the mean values did not differ.

3. The plasma and erythrocyte cholesterol-to-phospholipid molar ratios remained closely correlated (r = 0.77, P<0.01) before and after treatment, suggesting that S-adenosyl-l-methionine had not acted directly on the cells but rather had improved their lipoprotein milieu. Further support for this concept was provided by following one patient, who initially failed to respond, during an additional 3 weeks of S-adenosyl-l-methionine administration. The plasma cholesterol-to-phospholipid molar ratio fell steadily from week 1 to week 5 and was accompanied by a progressive decrease in the erythrocyte cholesterol-to-phospholipid molar ratio. Moreover, the initially suppressed acetylcholinesterase activity of the erythrocyte membranes returned towards normal during this period.

4. This preliminary study is the first evidence in jaundiced patients that a drug can help to reverse the deposition of cholesterol in an extrahepatic membrane. It merits, therefore, placebo-controlled, crossover investigations into the therapeutic potential of S-adenosyl-l-methionine in chronic liver disease.

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