Objective: CESD is a rare lysosomal disorder affecting intrahepatic colesterol hydrolysis lacking a specific treatment. Ezetimibe, a cholesterol absorption inhibitor, should represent an option never delivered as monotherapy. Methods: A 15 yrs old male patient affected by CESD, diagnosed on the basis of liver steato-fibrosis and LIPA gene mutation, was treated with 10 mg/die for 2 yrs. Biochemical parameters were checked at basal time,6 months,1, 2 yrs since starting therapy. Liver enzymes, lipid profile were tested by standard methods. Inflammatory markers of lipid peroxidation interleukins 1beta (IL1β) and 6 (IL6) were evaluated using western blot analyses. Tranforming growth factor-beta1 (Tgf-beta1), choosen as hepatic fibrosis parameter was evaluated by elisa kit. The serum protein adducts Malonaldehyde (MDA) and 4-hydroxynonenal (HNE) were analyzed to test the oxidative damage. Liver elastograpy employed to test liver fibrosis. Results: Liver enzymes normalized by 6 months of therapy; total cholesterol and LDL-C decreased by 30% and 25 % respectively at the same time. IL1β and IL6 decreased after one year of treatment. As well the oxidative markers malonaldehyde (MDA) and 4-hydroxynonenal (HNE) resulted 4,3 0.3 and 6.9± 0.7 AFU/mg protein in basal condition and 3.80.5 and 5.10.5 AFU/mgprotein after 1 yr treatment, so showing a normal value. Tgf-beta1 did not change in agreement with unchanged elastografic fibrosis. Conclusion: emphasis for CESD will lead to the disorder being recognized and correctly treated. Present results underline the well tolerated successful outcome reached by ezetimibe monotherapy in reducing lipoprotein levels, normalizing transaminases, cytokines and oxidative stress parameters.
The Treatment of Colesteryl Storage Disease (CESD) by Ezetimibe Monotherapy.
ABELLO, Francesca;GUARDAMAGNA, Ornella;
2010-01-01
Abstract
Objective: CESD is a rare lysosomal disorder affecting intrahepatic colesterol hydrolysis lacking a specific treatment. Ezetimibe, a cholesterol absorption inhibitor, should represent an option never delivered as monotherapy. Methods: A 15 yrs old male patient affected by CESD, diagnosed on the basis of liver steato-fibrosis and LIPA gene mutation, was treated with 10 mg/die for 2 yrs. Biochemical parameters were checked at basal time,6 months,1, 2 yrs since starting therapy. Liver enzymes, lipid profile were tested by standard methods. Inflammatory markers of lipid peroxidation interleukins 1beta (IL1β) and 6 (IL6) were evaluated using western blot analyses. Tranforming growth factor-beta1 (Tgf-beta1), choosen as hepatic fibrosis parameter was evaluated by elisa kit. The serum protein adducts Malonaldehyde (MDA) and 4-hydroxynonenal (HNE) were analyzed to test the oxidative damage. Liver elastograpy employed to test liver fibrosis. Results: Liver enzymes normalized by 6 months of therapy; total cholesterol and LDL-C decreased by 30% and 25 % respectively at the same time. IL1β and IL6 decreased after one year of treatment. As well the oxidative markers malonaldehyde (MDA) and 4-hydroxynonenal (HNE) resulted 4,3 0.3 and 6.9± 0.7 AFU/mg protein in basal condition and 3.80.5 and 5.10.5 AFU/mgprotein after 1 yr treatment, so showing a normal value. Tgf-beta1 did not change in agreement with unchanged elastografic fibrosis. Conclusion: emphasis for CESD will lead to the disorder being recognized and correctly treated. Present results underline the well tolerated successful outcome reached by ezetimibe monotherapy in reducing lipoprotein levels, normalizing transaminases, cytokines and oxidative stress parameters.
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