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New NAFLD Familial Risk Score Outperforms FIB-4 for Predicting Advanced Fibrosis in First-Degree Relatives


TLM 2023: The simple noninvasive tool may be an alternative to FIB-4, researchers said, and the new data may have implications for NAFLD surveillance.

A new risk score that identifies risk of metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in first-degree relatives of individuals with confirmed hepatic fibrosis outperformed the Fibrosis-4 (FIB-4) scoring index, according to study findings presented at The Liver Meeting 2023, November 10-14, 2023, in Boston MA.

The NAFLD Familiar Risk Score is based on a simple point system (for age, presence of type 2 diabetes [T2D], obesity, family history), that does not require laboratory investigations or advanced computation, according to presenting author Daniel Q Huang and colleagues. They note in the study abstract that although NAFLD-related fibrosis is heritable, how family history can be used to identify first-degree relatives with or at high risk for the disease is unclear. They designed the current prospective, cross-sectional multicenter study to create a new tool to accomplish that.

New NAFLD Familial Risk Score Outperforms FIB-4 for Predicting Advanced Fibrosis in First-Degree Relatives / image credit family ©jackfrog/stock.adobe.com

Huang et al recruited the derivation cohort from the US (University of California San Diego [USCD]) and the validation cohort from Helsinki, Finland, enrolling 242 adults with NAFLD and advanced fibrosis, NAFLD without advanced fibrosis, and without NAFLD, with 1 or more of their first-degree relatives. All participants were evaluated for liver fibrosis with most undergoing magnetic resonance elastography, according to the study. The team derived models to detect the presence of NAFLD with advanced fibrosis based on data from the USCD derivation cohort. To develop scoring based on a point system, they transformed coefficients from logistic univariate and multivariate regression models by integer rounding. External validation was then carried out in the validation (Helsinki) cohort.


The cohort of first-degree relatives numbered 396 participants (64% men). The group had a median age of 47 years and BMI of 27.6 kg/m2. Predictors of advanced fibrosis among the first-degree relatives in the derivation cohort (n=220) were age (1-point), T2D (1-point), obesity (2-points) and a proband with NAFLD and advanced fibrosis (2-points). These predictors then formed the NAFLDFamilial Risk score.

Huang et al reported area under the receiver operator characteristic curve (AUC) of the NAFLD Familial Risk score for detecting advanced fibrosis was 0.94 in the validation cohort (n=176). Based on AUC, the NAFLD Familial Risk score (0.94) outperformed the Fibrosis-4 index (0.70) (P=.02) in the validation cohort.

The NAFLD Familiar Risk Score, the investigators concluded, “is simple, does not require a calculator or extensive laboratory investigations, and may be a helpful alternative to FIB-4 for screening first-degree relatives. These data may have implications for surveillance in NAFLD.”

Source: Huang DQ, Ahlholm N, Luukkonen P, et al. Development and validation of the NAFLD familial risk score to detect advanced fibrosis: a prospective, multicenter study. Abstract presented at The Liver Meeting 2023; November 10-14, 2023; Boston, MA. https://www.aasld.org/the-liver-meeting/development-and-validation-nafld-familial-risk-score-detect-advanced-fibrosis

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