Diagnostic accuracy of AGILE 3+ score for advanced fibrosis in patients with NAFLD: A systematic review and meta-analysis

Abstract

Background and Aims: A simple non-invasive score, the Agile3+ score, combining liver stiffness measurement (LSM), aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for identification of advanced fibrosis in patients with suspected non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease (MASLD), so currently, the two terms are interchangeable. Methods: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the 24th of April 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤0.451) and rule-in (≥0.679) cut-offs. Results: We included 6 observational studies (total 6955 participants) with biopsy-proven NAFLD (mean age 53 [SE 4] years, mean BMI 30.9 [SE 2.3] Kg/m2, 54.0% men, prevalence of diabetes 59.6%). The pooled prevalence of advanced fibrosis (≥F3) was 42.1%. By the rule-out cut-off, the overall sensitivity and specificity were 88% (95%CI 81-93%; I2=89.2%) and 65% (95%CI 54-75%; I2=97.6%), respectively. By the rule-in cut-off, the overall sensitivity and specificity were 68% (95%CI 57-78%; I2=91.1%) and 87% (95%CI 80-92%; I2=96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age (p<0.01), BMI (p<0.01), and, although not statistically significant, sex (p=0.06). Conclusion: Our systematic review and meta-analysis suggest that Agile3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

Liver stiffness predicts progression to liver‐related events in patients with chronic liver disease – A cohort study of 14 414 patients

“…The time a patient has their baseline LSM might depend on the aetiology of disease and other parameters and should be taken into consideration when interpreting the results. Unfortunately, we lacked laboratory data for a majority of the cohort, thus being unable to compare the prognostic ability of LSM in combination with lab parameters such as Agile 3+, 39 or with the prognostic ability of other non-invasive biomarkers such as FIB-4. Since this was a register-based study, clinical parameters that can be important risk factors of progression of chronic liver disease, such as alcohol consumption or BMI, were also lacking.…”

Association between triglyceride to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease and liver fibrosis in American adults: an observational study from the National Health and Nutrition Examination Survey 2017–2020

“…Nonalcoholic fatty liver disease (NAFLD), as a globally prevalent metabolic-related disease of the liver, affects approximately 38% of the world’s population, and as such, it significantly threatens public health ( 1 ). Most patients with NAFLD do not experience discomfort, whereas a small percentage may present with fatigue, epigastric discomfort, or vague pain ( 2 ). While its typical characteristic include excessive lipid accumulation in the liver without alcohol abuse, some NAFLD patients can further progress to nonalcoholic steatohepatitis, liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma.…”

Reply to Letter to the Editor: “Patients with uncertain advanced fibrosis and cirrhosis diagnosis by Agile3+ and Agile4 scores cannot be excluded in validation studies”

“…In fact, meta-regression analyses on Agile3þ scores revealed that the diagnostic accuracy was partly mediated by age, body mass index, and sex, although sex did not reach statistical significance (p = 0.06). 4 The diagnostic performance of Agile scores in their Brazilian cohort appears to be poor, but they did not examine whether the clinical backgrounds affected their diagnostic performance, and this issue remains unclear. These factors could be identified and discussed in their future analyses.…”