Risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease

Nobuharu Tamaki; Noora Ahlholm; Panu K Luukkonen; Kimmo Porthan; Suzanne R Sharpton; Veeral Ajmera; Yuko Kono; Shravan Dave; Aijaz Ahmed; Vinay Sundaram; Michael J Wilkinson; Heather Patton; Hersh Gupta; Vanessa Cervantes; Christie Hernandez; Scarlett J Lopez; Ria Loomba; Amanda Baumgartner; Lisa Richards; Perttu Et Arkkila; Katriina Nemes; Helena Isoniemi; Hannele Yki-Järvinen; Rohit Loomba

doi:10.1172/JCI162513

Risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease

J Clin Invest. 2022 Nov 1;132(21):e162513. doi: 10.1172/JCI162513.

Authors

Nobuharu Tamaki^{1

2}, Noora Ahlholm^{3

4}, Panu K Luukkonen^{3

4

5}, Kimmo Porthan^{3

4}, Suzanne R Sharpton¹, Veeral Ajmera¹, Yuko Kono⁶, Shravan Dave⁶, Aijaz Ahmed⁷, Vinay Sundaram⁸, Michael J Wilkinson⁹, Heather Patton¹⁰, Hersh Gupta¹, Vanessa Cervantes¹, Christie Hernandez¹, Scarlett J Lopez¹, Ria Loomba¹, Amanda Baumgartner¹, Lisa Richards¹, Perttu Et Arkkila¹¹, Katriina Nemes^{3

12}, Helena Isoniemi¹², Hannele Yki-Järvinen^{3

4}, Rohit Loomba^{1

6

13}

Affiliations

¹ Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
² Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
³ Department of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
⁴ Minerva Foundation Institute for Medical Research, Helsinki, Finland.
⁵ Department of Internal Medicine, Yale University, New Haven, Connecticut, USA.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
⁷ Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.
⁸ Karsh Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁹ Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California, USA.
¹⁰ Gastroenterology Section, VA San Diego Healthcare System, San Diego, California, USA.
¹¹ Department of Gastroenterology and.
¹² Transplantation and Liver Surgery Unit, Abdominal Center, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
¹³ Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA.

Abstract

BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.

Keywords: Epidemiology; Fibrosis; Gastroenterology; Hepatology; Liver cancer.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Elasticity Imaging Techniques* / adverse effects
Elasticity Imaging Techniques* / methods
Fibrosis
Humans
Liver Cirrhosis / genetics
Male
Middle Aged
Non-alcoholic Fatty Liver Disease* / diagnostic imaging
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / genetics
Prospective Studies

Abstract

Publication types

MeSH terms

Grants and funding