The presence of two or more metabolic risk factors was associated with greater odds of steatosis and fibrosis, a cohort study found.
Among over 4,000 participants, those who had at least two metabolic factors based on metabolic-associated fatty liver disease (MAFLD) criteria were at significantly higher risk of developing steatosis (adjusted odds ratio [aOR] 5.79, 95% CI 3.98-8.43) and fibrosis (aOR 2.5, 95% CI 1.3-4.81), independent of high body mass index and diabetes status, reported Chirag Patel, PhD, of Harvard Medical School in Boston, and colleagues in Clinical Gastroenterology and Hepatology.
The top two metabolic factors for steatosis and fibrosis were:
- Insulin resistance: aORs of 3.96 for steatosis (95% CI 2.9-5.4) and 2.8 for fibrosis (95% CI 1.63-4.9)
- Greater central obesity: aORs of 5.98 (95% CI 4.54-7.87) and 4.43 (95% CI 2.9-6.7), respectively
“Given that fatty liver disease remains under-diagnosed in real-world settings and the challenge of deploying a screening heuristic requires laboratory tests, our findings highlight the potential of simplifying the MAFLD criteria/definition to identify the highest yield groups for screening and risk stratification,” the authors wrote.
“This study shines light on the factors that dominate the association (e.g., visceral adiposity, and insulin resistance) with steatosis and fibrosis, demonstrating that factors of high prevalence in the U.S. are also of highest risk for liver disease,” they added.
“We were surprised that waist circumference and insulin resistance played as large and independent roles even after considering body mass index and diabetes in steatosis and fibrosis risk,” Patel told MedPage Today. “A new definition has been proposed to screen populations for potential risk for liver disease … but it is unclear what risk factors that are currently in the definition play the largest or smallest role in the general U.S. population.”
The MAFLD criteria aim to improve patient stratification and management, but clinical factors used in its definition are complex, Patel’s group noted. This study was the first to examine the contribution of different metabolic factors in a nationally representative cohort, using 2017-2018 data from the National Health and Nutrition Examination Survey (NHANES) on 4,369 participants.
Of these, 2,732 were healthy adults, 1,234 had hepatic steatosis, and 403 had fibrosis. Mean age was 44-52, and 44-62% were men. Nearly two-thirds were white. Most had at least two metabolic factors (55-92%), and 7-40% had diabetes. Exclusion criteria included pregnancy and history of viral hepatitis, among others.
Patel and team evaluated the relative prognostic significance of seven key metabolic factors — waist circumference, insulin resistance, inflammation, blood pressure, plasma triglycerides, pre-diabetes, and high-density lipoprotein cholesterol level — defined by MAFLD criteria for steatosis and fibrosis outcomes, using separate models, which adjusted for demographics, diabetes, and overweight status.
Steatosis was defined by a controlled attenuation parameter at a higher sensitivity cutoff point (≥290 dB/m), and fibrosis was defined by a liver stiffness measurement ≥8.2 kPa. Insulin resistance was measured by the homeostatic model of insulin resistance (HOMA-IR ≥2.5), and larger waist circumference was defined as ≥102 cm and ≥90 cm for non-Asian and Asian men and ≥88 cm and ≥80 cm for non-Asian and Asian women.
When insulin resistance and larger waist circumference were added to the “diabetes and overweight” model, it improved accuracy in classifying steatosis, with an overall continuous net reclassification improvement (NRI) of 77% (45% for cases and 31% for non-cases), with an area under the curve (AUC) of 0.81.
Meanwhile, in the MAFLD model, having at least two metabolic factors, diabetes, and an overweight status improved the overall classification accuracy for hepatic steatosis with an overall continuous NRI of 65% — 82% for cases, but a reduced NRI of -17%, with an AUC of 0.79.
Patel and colleagues acknowledged that long-term data are needed to confirm their findings.
This study was supported by the National Institutes of Allergy and Infectious Disease, National Institutes of Environmental Health Science, and Optum Health.
Patel disclosed no conflicts of interest.
A co-author reported support from the Boston University School of Medicine Department of Medicine Career Investment, Boston University Clinical Translational Science Institute, Doris Duke Charitable Foundation, Gilead Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.