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By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.
“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”
To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.
Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.
Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.
Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.
When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).
“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”
Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.
“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”
The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.
My patients with metabolic dysfunction associated steatotic liver disease (MASLD) and advanced fibrosis and cirrhosis often worry about the risk of MASLD and advanced fibrosis among their relatives, especially their children and siblings. Based on my clinical experience, I tell them that their first-degree relatives get checked for MASLD with liver enzymes and a liver ultrasound. I advise if either of these tests is abnormal, they should see a gastroenterologist for further evaluation. In this paper, Huang and colleagues developed and validated a NAFLD Familial Risk Score to identify advanced fibrosis in the first-degree relatives of patients with NAFLD and advanced fibrosis. This score consists of age greater than 50 years (one point), BMI greater than 30 kg/m2 (two points), type 2 diabetes (one point), and a first-degree relative with NAFLD and advanced fibrosis (two points). 
Naga Chalasani, MD, AGAF, is a practicing hepatologist and David W. Crabb Professor of Gastroenterology and vice president for academic affairs at Indiana University School of Medicine and Indiana University Health in Indianapolis. He declared no conflicts of interests for this commentary.
My patients with metabolic dysfunction associated steatotic liver disease (MASLD) and advanced fibrosis and cirrhosis often worry about the risk of MASLD and advanced fibrosis among their relatives, especially their children and siblings. Based on my clinical experience, I tell them that their first-degree relatives get checked for MASLD with liver enzymes and a liver ultrasound. I advise if either of these tests is abnormal, they should see a gastroenterologist for further evaluation. In this paper, Huang and colleagues developed and validated a NAFLD Familial Risk Score to identify advanced fibrosis in the first-degree relatives of patients with NAFLD and advanced fibrosis. This score consists of age greater than 50 years (one point), BMI greater than 30 kg/m2 (two points), type 2 diabetes (one point), and a first-degree relative with NAFLD and advanced fibrosis (two points).
Naga Chalasani, MD, AGAF, is a practicing hepatologist and David W. Crabb Professor of Gastroenterology and vice president for academic affairs at Indiana University School of Medicine and Indiana University Health in Indianapolis. He declared no conflicts of interests for this commentary.
My patients with metabolic dysfunction associated steatotic liver disease (MASLD) and advanced fibrosis and cirrhosis often worry about the risk of MASLD and advanced fibrosis among their relatives, especially their children and siblings. Based on my clinical experience, I tell them that their first-degree relatives get checked for MASLD with liver enzymes and a liver ultrasound. I advise if either of these tests is abnormal, they should see a gastroenterologist for further evaluation. In this paper, Huang and colleagues developed and validated a NAFLD Familial Risk Score to identify advanced fibrosis in the first-degree relatives of patients with NAFLD and advanced fibrosis. This score consists of age greater than 50 years (one point), BMI greater than 30 kg/m2 (two points), type 2 diabetes (one point), and a first-degree relative with NAFLD and advanced fibrosis (two points).
Naga Chalasani, MD, AGAF, is a practicing hepatologist and David W. Crabb Professor of Gastroenterology and vice president for academic affairs at Indiana University School of Medicine and Indiana University Health in Indianapolis. He declared no conflicts of interests for this commentary.
By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.
“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”
To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.
Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.
Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.
Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.
When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).
“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”
Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.
“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”
The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.
By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.
“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”
To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.
Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.
Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.
Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.
When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).
“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”
Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.
“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”
The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY