title: Effects of Liver Transplantation on Lipids and Cardiovascular Disease in Children With Homozygous Familial Hypercholesterolemia.
abstract: Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited, life-threatening, metabolic disorder of low-density lipoprotein (LDL) receptor function characterized by elevated serum LDL cholesterol (LDL-C) and rapidly progressive atherosclerotic cardiovascular disease (ACVD). Since LDL receptors are predominantly found on hepatocytes, orthotopic liver transplantation (OLT) has emerged as a viable intervention for HoFH because LDL receptor activity is restored. This study assessed the effects of OLT on ACVD and ACVD risk factors in pediatric patients with HoFH. We analyzed lipids, lipoproteins, body mass index, glucose, blood pressure, and cardiovascular imaging in 8 pediatric patients who underwent OLT for HoFH. Total serum cholesterol, LDL-C, lipoprotein (a), and apolipoprotein B/apolipoprotein A1 ratio decreased to normal values in all subjects (p values <0.001) at 1 month after OLT and were maintained for the length of follow-up (2 to 6 years). There were few complications related to surgery or immunosuppressive therapy. Two patients developed mild hypertension. In the first 4 subjects monitored for 4 to 6 years after OLT, coronary artery disease did not develop or progress except in 1 minor artery in 1 subject and actually regressed in 2 subjects with >50% stenosis. However, aortic valve stenosis progressed in 2 of 4 subjects. In conclusion, OLT is an effective therapeutic option for patients with HoFH with coronary artery disease and persistently elevated serum LDL-C despite maximum medical therapy. Aortic valvular disease may progress. Long-term data are needed to evaluate the true risk-benefit ratio of this surgical approach.
authors.affiliation: Department of Pediatric Gastroenterology, Columbia University College of Physicians and Surgeons, New York, New York. Electronic address: mm2475@cumc.columbia.edu.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Department of Pediatric Gastroenterology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Brodlie
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Adam
authors.initials: A
authors.lastname: Griesemer
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Patricia
authors.initials: P
authors.lastname: Harren
authors.affiliation: The Rogosin Institute, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Bruce
authors.initials: B
authors.lastname: Gordon
authors.affiliation: The Rogosin Institute, New York, New York; Department of Biochemistry, Weill Cornell Medical College, New York, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Parker
authors.affiliation: The Rogosin Institute, New York, New York; Department of Biochemistry, Weill Cornell Medical College, New York, New York.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levine
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Theodore
authors.initials: T
authors.lastname: Tyberg
authors.affiliation: Department of Pediatric Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Starc
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Iksung
authors.initials: I
authors.lastname: Cho
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: James
authors.initials: J
authors.lastname: Min
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Elmore
authors.affiliation: Department of Pediatric Gastroenterology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Steven
authors.initials: S
authors.lastname: Lobritto
authors.affiliation: The Rogosin Institute, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Lisa Cooper
authors.initials: LC
authors.lastname: Hudgins
mesh_terms: D000293:Adolescent; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases; D002648:Child; D002675:Child, Preschool; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000072226:Computed Tomography Angiography; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000209:etiology; D005260:Female; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000601:surgery*; D017270:Lipoprotein(a) / Q000097:blood; D016031:Liver Transplantation; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a)