Lack of Cholesterol-Lowering Effect of Graded Doses of Cholestyramine in Children With Alagille Syndrome: A Pilot Study

Background: There is controversy about the potential risk of sustained high concentrations of cholesterol and triglyceride in patients with cholestatic chronic liver disease. However, it is currently accepted that cholesterol-lowering therapy may reduce morbidity and mortality rates in hypercholesterolemic patients without preexisting coronary heart disease, as well as in those with coronary heart disease. The objective of this study was to evaluate the effect of cholestyramine on the serum lipid profile of a group of children with Alagille syndrome and hypercholesterolemia. Methods: Five children with Alagille syndrome and basal serum cholesterol concentrations greater than 230 mg/dL were included. Total serum cholesterol, triglyceride, low-density, and high-density lipoprotein cholesterol concentrations were measured on days 0, 10, 20, and 30 after the administration of oral cholestyramine 100, 250, and 500 mg(kg.d), respectively. Lipid fractions were reported as mean ± 1 SD. Statistical analysis was performed with Friedman analysis of variance. Results: The basal values and those of the three 10-day subsequent 100-, 250-, and 500-mg(kg.d) cholestyramine periods were as follows: total cholesterol: 327.6 ± 77.1, 305.4 ± 52.1, 290.6 ± 24.1, and 320.6 ± 32.3, respectively (P = 0.668); triglyceride: 136.4 ± 14.6, 144.8 ± 41.3, 161 ± 30.9, and 165.4 ± 40.7, respectively (P = 0.356); low-density lipoprotein cholesterol: 245.4 ± 57.8, 239.8 ± 48.6, 242.2 ± 68.6, and 246.4 ± 49.5, respectively (P = 0.782); and high-density lipoprotein cholesterol: 44.4 ± 11.2, 41.8 ± 12.8, 44.6.2 ± 13.2, and 47 ± 8.5, respectively (P = 0.431). Conclusion: Under the conditions of the current study, no significant effect of variable doses of cholestyramine could be demonstrated on the serum lipid profile of a series of children with Alagille syndrome. While the controversy on the potential atherogenic risk of low-density lipoprotein hypercholesterolemia in patients with chronic liver disease persists, new, prospective pharmacologic or nutritional trials are required.