Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis.

Background: This study evaluated the effect of statins in Primary biliary cirrhosis (PBC) on endothelial function, anti-oxidant status and vascular compliance.

Methods: Primary biliary cirrhosis patients with hypercholesterolaemia were randomized to receive 20 mg simvastatin or placebo in a single blind, randomized controlled trial. Body mass index, blood pressure, glucose, liver function, lipid profile, immunoglobulin levels, serological markers of endothelial function and anti-oxidant status were measured as well as vascular compliance, calculated from pulse wave analysis and velocity, at recruitment and again at 3, 6, 9 and 12 months.

Results: Twenty-one PBC patients (F = 20, mean age = 55) were randomized to simvastatin 20 mg (n = 11) or matched placebo (n = 10). At completion of the trial, serum cholesterol levels in the simvastatin group were significantly lower compared with the placebo group (4.91 mmol/L vs. 6.15 mmol/L, P = 0.01). Low-density lipoprotein (LDL) levels after 12 months were also significantly lower in the simvastatin group (2.33 mmol/L vs. 3.53 mmol/L, P = 0.01). After 12 months of treatment, lipid hydroperoxides were lower (0.49 μmol/L vs. 0.59 μmol/L, P = 0.10) while vitamin C levels were higher (80.54 μmol/L vs. 77.40 μmol/L, P = 0.95) in the simvastatin group. Pulse wave velocity remained similar between treatment groups at 12 months (8.45 m/s vs. 8.80 m/s, P = 0.66). Only one patient discontinued medication owing to side effects. No deterioration in liver transaminases was noted in the simvastatin group.

Conclusions: Statin therapy in patients with PBC appears safe and effective towards overall reductions in total cholesterol and LDL levels. Our initial study suggests that simvastatin may also confer advantageous effects on endothelial function and antioxidant status.