The Journal of Clinical Investigation (Nov 2022)

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 E.T. Arkkila,
  • Katriina Nemes,
  • Helena Isoniemi,
  • Hannele Yki-Järvinen,
  • Rohit Loomba

Journal volume & issue
Vol. 132, no. 21

Abstract

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BACKGROUND A 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.METHODS This 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.RESULTS Prevalence 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).CONCLUSION First-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.FUNDING Supported 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.

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