Abstract | BACKGROUND & AIMS: METHODS: Human studies employed cohorts of LAL-deficient patients and NAFLD subjects. Rat experimental groups comprised ex vivo liver samples of wild type, NAFLD, LAL-deficient, and LAL-deficient rats receiving 4weeks of sebelipase alfa treatment. Hepatic (1)H MR spectroscopy was performed using 3T (human) and 7T (preclinical) MRI scanners to quantify hepatic cholesterol and triglyceride content. RESULTS: CE accumulation was identified in LAL deficiency in both human and preclinical studies. A significant decrease in hepatic CE was observed in LAL-deficient rats following treatment with sebelipase alfa. CONCLUSIONS: We demonstrate an entirely non-invasive method to identify and quantify the hepatic lipid signature associated with a rare genetic cause of fatty liver. The approach provides a more favorable alternative to repeated biopsy sampling for diagnosis and disease progression / treatment monitoring of patients with LAL deficiency and other disorders characterised by increased free cholesterol and/or cholesteryl esters.
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Authors | Peter E Thelwall, Fiona E Smith, Mark C Leavitt, David Canty, Wei Hu, Kieren G Hollingsworth, Christian Thoma, Michael I Trenell, Roy Taylor, Joseph V Rutkowski, Andrew M Blamire, Anthony G Quinn |
Journal | Journal of hepatology
(J Hepatol)
Vol. 59
Issue 3
Pg. 543-9
(Sep 2013)
ISSN: 1600-0641 [Electronic] Netherlands |
PMID | 23624251
(Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Cholesterol Esters
- Fatty Acids
- Recombinant Proteins
- Triglycerides
- LIPA protein, human
- Sterol Esterase
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Topics |
- Animals
- Cholesterol Esters
(metabolism)
- Disease Models, Animal
- Fatty Acids
(metabolism)
- Fatty Liver
(metabolism)
- Humans
- Liver
(metabolism)
- Magnetic Resonance Spectroscopy
- Male
- Non-alcoholic Fatty Liver Disease
- Prospective Studies
- Rats
- Rats, Sprague-Dawley
- Rats, Transgenic
- Recombinant Proteins
(therapeutic use)
- Sterol Esterase
(deficiency, genetics, therapeutic use)
- Triglycerides
(metabolism)
- Wolman Disease
(drug therapy, genetics, metabolism)
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