Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

Clinical Trial
. 2017 Jun 30;127(7):2697-2704.
doi: 10.1172/JCI93465. Epub 2017 Jun 19.

"VSports app下载" Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis

Cyrielle Caussy  1   2 , Meera Soni  1 , Jeffrey Cui  1 , Ricki Bettencourt  1   3 , Nicholas Schork  4 , Chi-Hua Chen  5 , Mahdi Al Ikhwan  1 , Shirin Bassirian  1 , Sandra Cepin  1 , Monica P Gonzalez  1 , Michel Mendler  6 , Yuko Kono  6 , Irine Vodkin  6 , Kristin Mekeel  7 , Jeffrey Haldorson  7 , Alan Hemming  7 , Barbara Andrews  6 , Joanie Salotti  1   6 , Lisa Richards  1   6 , David A Brenner  6 , Claude B Sirlin  8 , Rohit Loomba  1   3   6 ; Familial NAFLD Cirrhosis Research Consortium
Affiliations
Clinical Trial

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

Cyrielle Caussy (VSports注册入口) et al. J Clin Invest. .

"V体育官网入口" 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 VSports手机版. 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) V体育安卓版. .

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) V体育ios版. .

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 VSports最新版本. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients. .

Ucsd irb: 140084 V体育平台登录. .

Funding: National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH. VSports注册入口.

PubMed Disclaimer

Conflict of interest statement (VSports最新版本)

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures (V体育2025版)

Figure 1
Figure 1. Prevalence of advanced fibrosis in first-degree relatives of patients with NAFLD-cirrhosis and NAFLD without advanced fibrosis and non-NAFLD controls.
The prevalence of advanced fibrosis assessed by MRE (>3.63 kPa), expressed as percentage of individuals with advanced fibrosis among the first-degree relatives of probands with non-NAFLD (total n = 69; blue bar), NAFLD without advanced fibrosis (total n = 25; green bar), and NAFLD with cirrhosis (total n = 39; pink bar), was 1.4%, 12%, and 18%, respectively, which was both clinically and statistically significant (*P < 0.003 by Cochran-Armitage test for trend).
Figure 2
Figure 2. Distribution of factors associated with NAFLD and fibrosis in first-degree relatives of patients with NAFLD-cirrhosis.
The prevalence of each factor is expressed as percentage of first-degree relatives of patients with NAFLD-cirrhosis and without advanced fibrosis (blue bars; total n = 32) and percentage of first-degree relatives of patients with NAFLD-cirrhosis and advanced fibrosis (pink bars; total n = 7). DM, diabetes mellitus; HTN, hypertension. *P < 0.05 by χ2 test.
Figure 3
Figure 3. Risk of advanced fibrosis in first-degree relatives of NAFLD-cirrhosis patients.
Compared with non-NAFLD controls (n = 69), the OR of cirrhosis in first-degree relatives of NAFLD-cirrhosis patients (n = 39) was 14.9 (95% CI, 1.8–126.0, P = 0.0133). The cirrhosis risk remained statistically and clinically significant after adjustment for age, sex, Hispanic ethnicity (no/yes), BMI, and diabetes, with a multivariable-adjusted OR of 12.5 (95% CI, 1.1–146.1, P = 0.0438). ORs were assessed by unadjusted and multivariable-adjusted logistic regression analyses.
Figure 4
Figure 4. Representative MRE in a proband with NAFLD-cirrhosis and her first-degree relatives.
Representative MRE map of (A) a 73-year-old female with cirrhosis diagnosed with MRE of 4.36 kPa, (B) her 69-year-old brother with cirrhosis diagnosed with MRE of 4.3 kPa, and (C) her 66-year-old sister without cirrhosis excluded with MRE of 1.82.
Figure 5
Figure 5. PNPLA3 p.I148M minor G allele frequencies.
The allele frequency of PNPLA3 p.I148M minor variant G is expressed as percentage of minor allele G in probands with NAFLD-cirrhosis (pink bar; total n = 12 alleles) compared with non-NAFLD controls (blue bar; total n = 92 alleles) and percentage of first-degree relatives of patients with NAFLD-cirrhosis (pink bar; total n = 46 alleles) compared with first-degree relatives of controls (blue bar; total n = 88 alleles). P value was determined using a Fisher exact test or a χ2 test when appropriate.
See this image and copyright information in PMC

Comment in (V体育ios版)

References

    1. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):686–690. doi: 10.1038/nrgastro.2013.171. - DOI - PubMed
    1. Chalasani N, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005–2023. doi: 10.1002/hep.25762. - DOI - PubMed
    1. Angulo P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–97.e10. doi: 10.1053/j.gastro.2015.04.043. - DOI - PMC - PubMed
    1. Ekstedt M, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547–1554. doi: 10.1002/hep.27368. - DOI - PubMed
    1. Loomba R, Chalasani N. The hierarchical model of NAFLD: prognostic significance of histologic features in NASH. Gastroenterology. 2015;149(2):278–281. doi: 10.1053/j.gastro.2015.06.016. - DOI - PubMed

Publication types

MeSH terms