Journal article
Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis
The Journal of clinical investigation, Vol.127(7), pp.2697-2704
06/19/2017
DOI: 10.1172/JCI93465
PMCID: PMC5490764
PMID: 28628033
Abstract
BACKGROUND.
The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.
METHODS.
This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (
n
= 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).
RESULTS.
The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%,
P
= 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8–126.0,
P
= 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1–146.1,
P
= 0.0438).
CONCLUSION.
Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.
TRIAL REGISTRATION.
UCSD IRB: 140084.
FUNDING.
National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.
Details
- Title: Subtitle
- Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis
- Creators
- Cyrielle Caussy - University of California, San DiegoMeera Soni - University of California, San DiegoJeffrey Cui - University of California, San DiegoRicki Bettencourt - University of California, San DiegoNicholas Schork - J. Craig Venter InstituteChi-Hua Chen - Hospices Civils de LyonMahdi Al Ikhwan - Hospices Civils de LyonShirin Bassirian - University of California, San DiegoSandra Cepin - University of California, San DiegoMonica P. Gonzalez - University of California, San DiegoMichel Mendler - Hospices Civils de LyonYuko Kono - Hospices Civils de LyonIrine Vodkin - Hospices Civils de LyonKristin Mekeel - Hospices Civils de LyonJeffrey Haldorson - Hospices Civils de LyonAlan Hemming - Hospices Civils de LyonBarbara Andrews - Hospices Civils de LyonJoanie Salotti - University of California, San DiegoLisa Richards - University of California, San DiegoDavid A. Brenner - Hospices Civils de LyonClaude B. Sirlin - University of California, San DiegoRohit Loomba - University of California, San DiegoFamilial NAFLD Cirrhosis Research Consortium
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.127(7), pp.2697-2704
- DOI
- 10.1172/JCI93465
- PMID
- 28628033
- PMCID
- PMC5490764
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 06/19/2017
- Academic Unit
- Surgery
- Record Identifier
- 9984322959802771
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