Hepatotoxicity of Statins As Determined by Serum Alanine Aminotransferase in a Pediatric Cohort With Dyslipidemia

Overview

Journal J Pediatr Gastroenterol Nutr

Publisher Wiley

Date 2018 Oct 19

PMID 30334928

Citations 3

Authors

Nirav K Desai

Michael M Mendelson

Annette Baker

Heather H Ryan

Suzanne Griggs

Meera Boghani

Elizabeth Yellen

Lucy Buckley

Matthew W Gillman

Justin P Zachariah

Dionne Graham

Maureen M Jonas

Sarah D de Ferranti

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of the study was to evaluate the hepatotoxicity of statins, as determined by serum alanine aminotransferase (ALT), in children and adolescents with dyslipidemia in real-world clinical practice.

Study Design: Clinical and laboratory data were prospectively collected between September 2010 and March 2014. We compared ALT levels between patients prescribed versus not prescribed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), and then compared ALT before and after initiation of statins.

Results: Over the 3.5-year observation period, there were 2704 ALT measurements among 943 patients. The mean age was 14 years; 54% were boys, 47% obese, and 208 patients were treated with statins. Median follow-up after first ALT was 18 months. The mean (SD) ALT in statin and non-statin users was 23 (20) U/L and 28 (28) U/L, respectively. In models adjusted for age, sex, and race, ALT was 2.1 U/L (95% CI 0.1 to 4.4; P = 0.04) lower among statin users, which was attenuated after adjustment for weight category. Patients started on statins during the observation period did not demonstrate an increase in ALT over time (ALT 0.9 U/L [95% confidence interval -5.2 to 3.4] increase per year; P = 0.7).

Conclusions: In our study population, we did not observe a higher burden of ALT elevations among pediatric patients on statins as compared to those with dyslipidemia who are not on statins, supporting the hepatic safety of statin use in childhood.

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References

Bader T . The myth of statin-induced hepatotoxicity. Am J Gastroenterol. 2010; 105(5):978-80. DOI: 10.1038/ajg.2010.102. View

Vos M, Abrams S, Barlow S, Caprio S, Daniels S, Kohli R . NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology.... J Pediatr Gastroenterol Nutr. 2017; 64(2):319-334. PMC: 5413933. DOI: 10.1097/MPG.0000000000001482. View

Braamskamp M, Langslet G, McCrindle B, Cassiman D, Francis G, Gagne C . Efficacy and safety of rosuvastatin therapy in children and adolescents with familial hypercholesterolemia: Results from the CHARON study. J Clin Lipidol. 2015; 9(6):741-750. DOI: 10.1016/j.jacl.2015.07.011. View

Chalasani N . Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology. 2005; 41(4):690-5. DOI: 10.1002/hep.20671. View

Avis H, Hutten B, Gagne C, Langslet G, McCrindle B, Wiegman A . Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. J Am Coll Cardiol. 2010; 55(11):1121-6. DOI: 10.1016/j.jacc.2009.10.042. View

Herrick C, Bahrainy S, Gill E . Statins and the liver. Cardiol Clin. 2015; 33(2):257-65. DOI: 10.1016/j.ccl.2015.02.005. View

. Prevalence of abnormal lipid levels among youths --- United States, 1999-2006. MMWR Morb Mortal Wkly Rep. 2010; 59(2):29-33. View

Braamskamp M, Wijburg F, Wiegman A . Drug therapy of hypercholesterolaemia in children and adolescents. Drugs. 2012; 72(6):759-72. DOI: 10.2165/11632810-000000000-00000. View

Belay B, Belamarich P, Tom-Revzon C . The use of statins in pediatrics: knowledge base, limitations, and future directions. Pediatrics. 2007; 119(2):370-80. DOI: 10.1542/peds.2006-0787. View

10.

Vuorio A, Kuoppala J, Kovanen P, Humphries S, Strandberg T, Tonstad S . Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev. 2010; (7):CD006401. DOI: 10.1002/14651858.CD006401.pub2. View

11.

Stein E, Illingworth D, Kwiterovich Jr P, Liacouras C, Siimes M, Jacobson M . Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. JAMA. 1999; 281(2):137-44. DOI: 10.1001/jama.281.2.137. View

12.

Rzouq F, Volk M, Hatoum H, Talluri S, Mummadi R, Sood G . Hepatotoxicity fears contribute to underutilization of statin medications by primary care physicians. Am J Med Sci. 2010; 340(2):89-93. DOI: 10.1097/MAJ.0b013e3181e15da8. View

13.

Athyros V, Tziomalos K, Gossios T, Griva T, Anagnostis P, Kargiotis K . Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet. 2010; 376(9756):1916-22. DOI: 10.1016/S0140-6736(10)61272-X. View

14.

Taylor F, Huffman M, Macedo A, Moore T, Burke M, Davey Smith G . Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013; (1):CD004816. PMC: 6481400. DOI: 10.1002/14651858.CD004816.pub5. View

15.

de Jongh S, Ose L, Szamosi T, Gagne C, Lambert M, Scott R . Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. Circulation. 2002; 106(17):2231-7. DOI: 10.1161/01.cir.0000035247.42888.82. View

16.

McCrindle B, Ose L, Marais A . Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr. 2003; 143(1):74-80. DOI: 10.1016/S0022-3476(03)00186-0. View

17.

. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011; 128 Suppl 5:S213-56. PMC: 4536582. DOI: 10.1542/peds.2009-2107C. View

18.

Bays H, Cohen D, Chalasani N, Harrison S, The National Lipid Associations Statin Safety Task Force . An assessment by the Statin Liver Safety Task Force: 2014 update. J Clin Lipidol. 2014; 8(3 Suppl):S47-57. DOI: 10.1016/j.jacl.2014.02.011. View

19.

Macedo A, Taylor F, Casas J, Adler A, Prieto-Merino D, Ebrahim S . Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med. 2014; 12:51. PMC: 3998050. DOI: 10.1186/1741-7015-12-51. View

20.

Herrick C, Bahrainy S, Gill E . Statins and the Liver. Endocrinol Metab Clin North Am. 2016; 45(1):117-28. DOI: 10.1016/j.ecl.2015.09.008. View