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Abstract Details
Development and Validation of the Nonalcoholic Fatty Liver Disease Familial Risk Score to Detect Advanced Fibrosis: A Prospective, Multicenter Study
1Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore.
2Department of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
3Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California.
4Department of Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland; Transplantation and Liver Surgery Unit, Abdominal Center, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
5Transplantation and Liver Surgery Unit, Abdominal Center, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
6Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California. Electronic address: roloomba@ucsd.edu.
Abstract
Background & aims: Nonalcoholic fatty liver disease (NAFLD)-related fibrosis is heritable, but it is unclear how family history may be used to identify first-degree relatives with advanced fibrosis. We aimed to develop and validate a simple risk score to identify first-degree relatives of probands who have undergone assessment of liver fibrosis who are at higher risk of NAFLD with advanced fibrosis.
Methods: This prospective, cross-sectional, familial study consisted of a derivation cohort from San Diego, California, and a validation cohort from Helsinki, Finland. This study included consecutive adult probands (n = 242) with NAFLD and advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 of their first-degree relatives. All included probands and first-degree relatives underwent evaluation of liver fibrosis, the majority by magnetic resonance elastography.
Results: A total of 396 first-degree relatives (64% male) were included. The median age and body mass index were 47 years (interquartile range, 32-62 y) and 27.6 kg/m2 (interquartile range, 24.1-32.5 kg/m2), respectively. Age (1 point), type 2 diabetes (1 point), obesity (2 points), and proband with NAFLD and advanced fibrosis (2 points) were predictors of advanced fibrosis among first-degree relatives in the derivation cohort (n = 220) and formed the NAFLD Familial Risk Score. The area under the receiver operator characteristic curve of the NAFLD Familial Risk Score for detecting advanced fibrosis was 0.94 in the validation cohort (n = 176). The NAFLD Familial Risk Score outperformed the Fibrosis-4 index in the validation cohort (area under the receiver operator characteristic curve, 0.94 vs 0.70; P = .02).
Conclusions: The NAFLD Familial Risk Score is a simple and accurate clinical tool to identify advanced fibrosis in first-degree relatives. These data may have implications for surveillance in NAFLD.