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Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis
- Caussy, Cyrielle;
- Soni, Meera;
- Cui, Jeffrey;
- Bettencourt, Ricki;
- Schork, Nicholas;
- Chen, Chi-Hua;
- Ikhwan, Al;
- Bassirian, Shirin;
- Cepin, Sandra;
- Gonzalez, Monica P;
- Mendler, Michel;
- Kono, Yuko;
- Vodkin, Irine;
- Mekeel, Kristin;
- Haldorson, Jeffrey;
- Hemming, Alan;
- Andrews, Barbara;
- Salotti, Joanie;
- Richards, Lisa;
- Brenner, David A;
- Sirlin, Claude B;
- Loomba, Rohit
- et al.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490764/pdf/jci-127-93465.pdfNo data is associated with this publication.
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.