Apolipoprotein C-III in association with metabolic-dysfunction associated steatotic liver disease: A large, multicenter study
- PMID: 39442390
- DOI: 10.1016/j.clnu.2024.10.007
Apolipoprotein C-III in association with metabolic-dysfunction associated steatotic liver disease: A large, multicenter study
Abstract
Background & aims: The available literature on the effect of apolipoprotein C-III (ApoC-III) inhibition in MASLD reveals inconsistencies. The aim of the present work was to examine levels of ApoC-III in the entire spectrum of metabolic-dysfunction associated steatotic liver disease (MASLD).
Methods: This is a multicenter study involving patients enrolled in two gastroenterology-hepatology clinics (Greece and Australia) and in a bariatric-metabolic surgery clinic (Italy), with liver biopsy before and after bariatric surgery or lifestyle modification.
Results: Comparing simple MASL to steatohepatitis (MASH) with fibrosis stage F ≥ 2 (at-risk MASH), revealed a marginally significant trend for decreased ApoC-III levels in the latter group (p = 0.07). Multi-adjusted analysis revealed an inverse association between ApoC-III and at-risk MASH (Odds Ratioper 1 mg/dL increase in ApoC-III = 0.91, 95 % Confidence Interval (0.83, 0.99)). ApoC-III interacted with triglycerides in predicting at-risk MASH (p-for-interaction = 0.002). Participants with ApoC-III > median (∼3.75 mg/dL) and normal triglycerides (triglyceridese≤150 mg/dL) had the lowest likelihood to present at-risk MASH (31.8 %) in contrast with participants with ApoC-III < median and hypertriglyceridemia among whom at-risk MASH was recorded in 57.1 %. In multi-adjusted analysis participants with normal triglycerides and high ApoC-III had 64 % lower odds of at-risk MASH compared with their counterparts with ApoC-III < median (OR = 0.36, 95%CI (0.14, 0.86)). Among participants with hypertriglyceridemia, those with ApoC-III < median had less prevalent at-risk MASH compared with those with ApoC-III ≥ median (OR = 0.54, 95%CI (0.32, 0.98)); however in all cases significance was lost when liver enzymes were taken into account.
Conclusions: In advanced disease stages, ApoC-III levels seem to be decreased and advanced organ damage may be a potential explanation. Mendelian randomization studies are needed to confirm or refute this hypothesis.
Keywords: Apolipoprotein; Fatty liver disease; Lipids; Liver fibrosis; NAFLD.
Published by Elsevier Ltd.
Conflict of interest statement
Conflict of interest CSM reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingellheim, has been a shareholder of and has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Genfit, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal and Regeneron, reports educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to the work presented herein. JG is supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia Grant (APP1053206), Project, Ideas and Investigator grants (APP2001692, APP1107178, APP1108422, APP1196492) and a Cancer Institute NSW grant (2021/ATRG2028). GP has served as Advisor and/or Lecturer for Abbvie, Albireo, Amgen, Dicerna, Elpen, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Novo Nordisk, Roche and Takeda and has received research grants from Abbvie, Gilead and Takeda.
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