Study Estimates MASLD-Related Fibrosis, Cirrhosis Prevalence Using AGILE Scoring

Naim Alkhouri, MD

Credit: Naim Alkhouri on X

Findings from a recent study are providing clinicians with an overview of the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related advanced fibrosis and cirrhosis in the US based on AGILE 3 + and AGILE 4 scores.¹

The study leveraged National Health and Nutrition Examination Survey (NHANES) 2017-2018 transient elastography data to calculate AGILE 3 + and AGILE 4 scores for advanced fibrosis and cirrhosis, respectively, in participants with MASLD. Based on calculations from the new noninvasive scoring systems, investigators estimated approximately 4.5 million people in the US have advanced fibrosis and 0.6 million have cirrhosis due to MASLD.¹

“Liver biopsy has been the gold standard to determine the prevalence of MASLD fibrosis and cirrhosis; however, several noninvasive tests and scoring systems have been developed to estimate the prevalence of the two entities,” Naim Alkhouri, MD, chief medical officer, chief of transplant hepatology, and director of the Fatty Liver Program at Arizona Liver Health, and colleagues wrote.¹ “Owing to relying on routine blood tests alone, the accuracy of these tests can be easily affected by several factors that are not related to liver disease. More importantly, the positive predictive value of these tests is relatively low, leading to potentially overestimating the true disease prevalence.”

The AGILE scoring system includes AGILE 3 + and AGILE 4, non-proprietary tests that can be calculated using routinely collected clinical, elastography, and laboratory parameters. Specifically, they leverage liver stiffness measurement, AST/ALT ratio, platelets, sex and diabetes status, as well as age for AGILE 3 +. Developed in order to optimize the positive predictive value of noninvasive testing for cirrhosis and advanced fibrosis, the scores seek to provide fewer indeterminate results without the need for liver biopsy.²

To estimate the prevalence of MASLD-related advanced fibrosis and cirrhosis using AGILE 3 + and AGILE 4 scores, investigators included NHANES 2017-2018 participants ≥ 18 years of age with vibration-controlled transient elastography (VCTE) results as measured by FibroScan. Pregnant women and patients with excessive alcohol intake, hepatitis B/C, and ALT or AST > 500 IU/L were excluded.¹

Investigators defined MASLD as a controlled attenuation parameter (CAP) score ≥ 248 dB/m. Advanced fibrosis in patients with MASLD was estimated using AGILE 3 + and was assessed based on the following criteria: < 0.45 as rule out; 0.45–0.68 as indeterminate; and ≥ 0.68 as rule in to identify advanced fibrosis in MASLD patients. Cirrhosis was determined using AGILE 4 scoring based on the following criteria: < 0.25 as rule out; 0.25–0.57 as indeterminate; and ≥ 0.57 as rule in.¹

In total, 1244 subjects with MASLD were included in the final analysis. Among the cohort, the median age was 52.5 years, 54.9% were male, and 64.2% were White. Type 2 diabetes and obesity were observed among 36.2% and 59.4% of patients, respectively.¹

Based on AGILE 3+, investigators determined 80.3% of the cohort was at low risk for advanced fibrosis and 11.5% were in the grey zone. The overall prevalence of advanced fibrosis due to MASLD was 8.1%, corresponding to 4.5 million US patients.¹

Compared to those without advanced fibrosis, the rule-in population tended to be older (64.4 vs 49.6 years; P <.001) and have a greater BMI (37.9 vs 32; P <.001) with a significantly increased prevalence of type 2 diabetes (86% vs 24.3%; P <.001) and obesity (80.1% vs 56.4% P = .001). Those with advanced fibrosis also tended to have slightly greater AST (26.04 vs 21.13 IU/L; P = .012) and hemoglobin A1C (6.78 vs 5.92%; P <.001), but remarkably lower platelet count (201.69 vs 252.21 per 10^3 cells/uL; P <.001). Moreover, those with advanced had significantly greater LSM measurement (16.65 vs 5.25 kPa; P <.001), CAP (331.38 vs 304.61 dB; P <.001), and FAST score (0.35 vs 0.12; P <.001) compared to those without.¹

Based on AGILE 4, investigators determined 96.5% of the cohort was at low risk for cirrhosis and 2.4% were in the grey zone. The overall prevalence of MASLD-related cirrhosis was 1.1%, corresponding to 610,000 US patients.¹

Compared to those without MASLD-cirrhosis, the rule-in population tended to be older (54.5 vs 52.3 years) and have a greater BMI (44.7 vs 32.4; P <.001) with a significantly increased prevalence of type 2 diabetes (85.1% vs 34.9%; P = .011) and obesity (95.6% vs 58.3%; P <.001). Those with cirrhosis tended to have slightly elevated AST (27.89 vs 21.5 IU/L; P = .082) and hemoglobin A1C (6.54 vs 6.09%; P = .117) but remarkably lower platelet count (175.8 vs 246.71 per 10^3 cells/uL; P <.001). Similar to those with fibrosis, participants with cirrhosis had significantly greater LSM measurement (37.22 vs 5.75 kPa; P <.001), FAST score (0.52 vs 0.15; P <.001), and CAP (318.73 vs 307.75 dB; P = .011).¹

Investigators acknowledged limitations to these findings related to the nature of the AGILE scoring system; uncertainties regarding whether the selected population is representative of the US population as a whole; and potential variations in the cutoff for steatosis.¹

“It is crucial to balance the accuracy of the diagnostic tools and the feasibility of obtaining the diagnostic information in population-based epidemiological studies like this,” investigators concluded.¹

References

1. ^{Alkhouri N, Almomani A, Le P, et al. The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related advanced fibrosis and cirrhosis in the United States population utilizing AGILE 3 + and AGILE 4 scores: analysis of the NHANES 2017–2018 cycle. https://doi.org/10.1186/s12876-024-03295-8}
2. ^{Sanyal AJ, Foucquier J, Younossi ZM, et al. Enhanced diagnosis of advanced fibrosis and cirrhosis in individuals with NAFLD using FibroScan-based Agile scores. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2022.10.034}