Long-term outcomes of liver transplantation for homozygous familial hypercholesterolaemia in Australia and New Zealand.

Journal

Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 16 06 2023
revised: 14 09 2023
accepted: 20 09 2023
pubmed: 21 10 2023
medline: 21 10 2023
entrez: 20 10 2023
Statut: ppublish

Résumé

Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort. Newer drugs including lomitapide and evinacumab might reduce the need for apheresis and LT. We sought to determine the long-term outcomes following LT in Australia and New Zealand. We analysed demographic, biochemical and clinical data from all patients in Australia and New Zealand who have received LT for homozygous FH, identified from the Australia and New Zealand Liver and Intestinal Transplant Registry. Nine patients (five female; one deceased; seven aged between 3 and 6 years at the time of LT and two aged 22 and 26 years) were identified. Mean follow-up was 14.1 years (range 4-27). Baseline LDL-cholesterol off all treatment was 23 ± 4.1 mmol/L. Mean LDL-cholesterol on medical therapy (including maximal statin therapy in all patients, ezetimibe in three and LA in five) was 11 ± 5.7 mmol/L (p < 0.001). After LT, mean LDL-cholesterol was 2.6 ± 0.9 mmol/L (p = 0.004) with three patients remaining on statin therapy and none on LA. One patient died from acute myocardial infarction (AMI) three years after LT. Two patients required aortic valve replacement, more than 10 years after LT. The remaining six patients were asymptomatic after eight to 21 years of follow-up. No significant adverse events associated with immunosuppression were reported. LT for homozygous FH was highly effective in achieving substantial long-term reduction in LDL-cholesterol concentrations in all nine patients. LT remains an option for severe cases of homozygous FH where drug therapy combined with apheresis is ineffective or unfeasible.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort. Newer drugs including lomitapide and evinacumab might reduce the need for apheresis and LT. We sought to determine the long-term outcomes following LT in Australia and New Zealand.
METHODS METHODS
We analysed demographic, biochemical and clinical data from all patients in Australia and New Zealand who have received LT for homozygous FH, identified from the Australia and New Zealand Liver and Intestinal Transplant Registry.
RESULTS RESULTS
Nine patients (five female; one deceased; seven aged between 3 and 6 years at the time of LT and two aged 22 and 26 years) were identified. Mean follow-up was 14.1 years (range 4-27). Baseline LDL-cholesterol off all treatment was 23 ± 4.1 mmol/L. Mean LDL-cholesterol on medical therapy (including maximal statin therapy in all patients, ezetimibe in three and LA in five) was 11 ± 5.7 mmol/L (p < 0.001). After LT, mean LDL-cholesterol was 2.6 ± 0.9 mmol/L (p = 0.004) with three patients remaining on statin therapy and none on LA. One patient died from acute myocardial infarction (AMI) three years after LT. Two patients required aortic valve replacement, more than 10 years after LT. The remaining six patients were asymptomatic after eight to 21 years of follow-up. No significant adverse events associated with immunosuppression were reported.
CONCLUSIONS CONCLUSIONS
LT for homozygous FH was highly effective in achieving substantial long-term reduction in LDL-cholesterol concentrations in all nine patients. LT remains an option for severe cases of homozygous FH where drug therapy combined with apheresis is ineffective or unfeasible.

Identifiants

DOI: 10.1016/j.atherosclerosis.2023.117305 PMID: 37863699
pubmed: 37863699
pii: S0021-9150(23)05226-7
doi: 10.1016/j.atherosclerosis.2023.117305
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

117305

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Michael M Page (MM)

Medical School, The University of Western Australia, Perth, Australia; Western Diagnostic Pathology, Perth, Australia.

Winita Hardikar (W)

Gastroenterology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.

George Alex (G)

Gastroenterology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.

Sue Bates (S)

Gastroenterology and Clinical Nutrition, The Royal Children's Hospital Melbourne, Melbourne, Australia.

Shubha Srinivasan (S)

Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

Michael Stormon (M)

Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Gastroenterology and Hepatology, The Children's Hospital at Westmead, Sydney, Australia.

Kat Hall (K)

Hepatobiliary and Liver Transplant Surgery Unit, Austin Health, Melbourne, Australia.

Helen M Evans (HM)

Paediatric Gastroenterology and Hepatology, Starship Child Health, Auckland, New Zealand; Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.

Peter Johnston (P)

New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.

John Chen (J)

South Australia Liver Transplant Unit, Flinders Medical Centre, Adelaide, Australia; College of Medicine and Public Health, Flinders University, Adelaide, Australia.

Alan Wigg (A)

South Australia Liver Transplant Unit, Flinders Medical Centre, Adelaide, Australia; College of Medicine and Public Health, Flinders University, Adelaide, Australia.

Libby John (L)

South Australia Liver Transplant Unit, Flinders Medical Centre, Adelaide, Australia.

Elif I Ekinci (EI)

Department of Endocrinology, Austin Health, Melbourne, Australia; The Australian Centre for Accelerating Diabetes Innovation, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia; Department of Medicine, Austin Health, Melbourne Medical School, The University of Melbourne, Melbourne, Australia.

Richard C O'Brien (RC)

Department of Endocrinology, Austin Health, Melbourne, Australia; Department of Medicine, Austin Health, Melbourne Medical School, The University of Melbourne, Melbourne, Australia.

Robert Jones (R)

Hepatobiliary and Liver Transplant Surgery Unit, Austin Health, Melbourne, Australia; Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia.

Gerald F Watts (GF)

Medical School, The University of Western Australia, Perth, Australia; Department of Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia. Electronic address: gerald.watts@uwa.edu.au.

Classifications MeSH