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Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis.

  • Author(s): Caussy, Cyrielle
  • Soni, Meera
  • Cui, Jeffrey
  • Bettencourt, Ricki
  • Schork, Nicholas
  • Chen, Chi-Hua
  • Ikhwan, Mahdi 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
  • Familial NAFLD Cirrhosis Research Consortium
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490764/pdf/jci-127-93465.pdf
No 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.

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