Population-specific cut-off points of fatty liver index for the diagnosis of hepatic steatosis

Recently, metabolic dysfunction-associated fatty liver disease (MAFLD)[1]Eslam M. Newsome P.N. Sarin S.K. Anstee Q.M. Targher G. Romero-Gomez M. et al.A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020; 73: 202-209Abstract Full Text Full Text PDF PubMed Scopus (616) Google Scholar was proposed by an international panel of experts from 22 countries to replace non-alcoholic fatty liver disease (NAFLD). In this statement,[1]Eslam M. Newsome P.N. Sarin S.K. Anstee Q.M. Targher G. Romero-Gomez M. et al.A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020; 73: 202-209Abstract Full Text Full Text PDF PubMed Scopus (616) Google Scholar positive diagnostic criteria for MAFLD were proposed. In the diagnostic flowchart, the diagnosis of hepatic steatosis (HS) was the first step. Of the 3 methods highlighted for the diagnosis of HS, liver biopsy is the gold standard but invasive, abdominal ultrasonography is currently the most widely used first-line imaging technique,[2]Eslam M. Sarin S.K. Wong V.W. Fan J.G. Kawaguchi T. Ahn S.H. et al.The Asian Pacific Association for the Study of the Liver Clinical Practice Guidelines for the diagnosis and management of metabolic associated fatty liver disease.Hepatol Int. 2020 Dec; 14: 889-919Crossref PubMed Scopus (99) Google Scholar and fatty liver index (FLI) is the only blood biomarker mentioned, but no specific cut-off points were given. FLI is a simple algorithm developed by Bedogni et al.[3]Bedogni G. Bellentani S. Miglioli L. Masutti F. Passalacqua M. Castiglione A. et al.The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population.BMC Gastroenterol. 2006; 6: 33Crossref PubMed Scopus (1090) Google Scholar for the prediction of fatty liver in the general population. It comprises 4 components: waist circumference (WC), body mass index (BMI), triglycerides, and gamma-glutamyltransferase (GGT). In Bedogni et al.’s paper,[3]Bedogni G. Bellentani S. Miglioli L. Masutti F. Passalacqua M. Castiglione A. et al.The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population.BMC Gastroenterol. 2006; 6: 33Crossref PubMed Scopus (1090) Google Scholar gender was not found to be associated with fatty liver in final model. However, our preliminary study of 135,436 physical examination patients showed a significant difference in the optimal cut-off points of FLI for the diagnosis of HS between Chinese males and females, 37.25 (sensitivity = 81.23%, AUROC = 0.856) and 17.00 (sensitivity = 85.94%, AUROC = 0.909), respectively.[4]Xu Z. Li H. Tian S. Wu J. Li X. Liu Z.L. et al.Blood biomarkers for the diagnosis of hepatic steatosis in metabolic dysfunction-associated fatty liver disease.J Hepatol. 2020; 73: 1264-1265Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Why is there such a gap between men and women? The main differences were found in WC and BMI, both of which are integral to the calculation of FLI and are generally thought to be closely associated with the development of metabolic diseases, with different thresholds in men and women. This study enrolled a total of 135,356 participants, including 59,569 (44%) females and 75,787 (56%) males, who underwent health examination at the Health Management Center of The First Affiliated Hospital of Chongqing Medical University, between January 2015 and September 2018. 27.26% of these participants were diagnosed with HS by ultrasound, and the prevalence rate of HS in females (15.2%) was significantly lower than that in males (36.8%). Based on the BMI and WC criteria for Asians developed by the World Health Organization,[5]World Health Organization. Regional Office for the Western PacificThe Asia-Pacific perspective : redefining obesity and its treatment. Health Communications Australia, Sydney2000Google Scholar,[6]World Health OrganizationWaist circumference and waist-hip ratio : report of a WHO expert consultation, Geneva, 8-11 December 2008.2011Google Scholar BMI was divided into 4 groups: underweight (<18.5 kg/m2), normal (≥18.5 kg/m2 and <23.0 kg/m2), overweight (≥23.0 kg/m2 and <25.0 kg/m2) and obese (≥25.0 kg/m2), and WC was divided into normal (≤80 in female and ≤90 in male) and abnormal (>80 in female and >90 in male). Taking the HS diagnosed by abdomen ultrasonography in the fasting state as the reference standard, the optimal cut-off points of FLI were obtained from ROC curve analysis. After stratification by WC and BMI, the AUROCs of FLI were all greater than 0.700, except in overweight men with WC >90, suggesting that FLI had acceptable diagnostic ability for the diagnosis of HS. There was a huge difference in the optimal cut-off points of FLI between normal (≤80 in female and ≤90 in male) and abnormal WC groups, especially in men (28.66 vs. 60.94). Consistent with a previous study, the cut-off point of FLI for the diagnosis of HS is generally lower in women than in men. With the increase of BMI, the FLI value increases gradually in both men and women. Detailed data are presented in Table S1. Taking gender, WC and BMI into consideration, population-specific cut-off points of FLI for the diagnosis of HS are tabulated (Table 1). A diagnosis of fatty liver can be considered if a specific FLI value is greater than the cut-off point which is shown in Table 1 in the same condition.Table 1The cut-off points of FLI stratified by WC and BMI.GenderCut-off pointsBMI<18.518.5≤BMI<23.023.0≤BMI<25.0BMI≥25.0Male16.1117.1731.8557.16 WC ≤9028.6616.1117.0631.9047.05 WC >9060.94-∗The optimal cut-off point of FLI could not be obtained owing to insufficient data. FLI, fatty liver index; WC, waist circumference.37.6649.8260.89Female4.449.6218.7139.00 WC ≤8011.024.448.4217.7227.27 WC >8028.90-∗The optimal cut-off point of FLI could not be obtained owing to insufficient data. FLI, fatty liver index; WC, waist circumference.17.2921.7240.29The cut-off points of FLI and corresponding sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, Youden index and area under the receiver operating characteristic curve (AUROC) were performed with MedCalc version 19.0.7.∗ The optimal cut-off point of FLI could not be obtained owing to insufficient data. FLI, fatty liver index; WC, waist circumference. Open table in a new tab The cut-off points of FLI and corresponding sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, Youden index and area under the receiver operating characteristic curve (AUROC) were performed with MedCalc version 19.0.7. Currently, FLI is the most acknowledged serological index for the diagnosis of HS, which may hopefully contribute to the diagnosis of MAFLD and have its own clinical value in large epidemiological investigations or when ultrasound is inaccessible; but, how to use it to diagnose fatty liver is controversial. The original cut-off point of FLI proposed by Bedogni et al. without any stratified restrictions was difficult to apply in practice. In this study, relatively accurate and detailed diagnostic cut-off values of FLI are obtained by using large-scale data, and this study demonstrates that gender, WC and BMI should be taken into consideration when using FLI, as the cut-off points of FLI vary with them. Certainly, further studies are warranted to explore more accurate FLI cut-off points or other blood biomarkers to diagnose HS. The authors received no financial support to produce this manuscript. All authors contributed to the study conception and design. Material preparation and data collection were performed by Juan Wu, Hao Li. Analysis was performed by Juan Wu and Zhou Xu. The first draft of the manuscript was written by Juan Wu, Hao Li and all authors commented on previous versions of the manuscript. Ling-quan Kong and Liang Ran directed the concept and design of the study and revised the manuscript. All authors read and approved the final manuscript. All data, models, or code generated or used during the study are available from the corresponding author by request. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following are the supplementary data to this article: Download .pdf (.25 MB) Help with pdf files Multimedia component 1 Download .pdf (.16 MB) Help with pdf files Multimedia component 2 Download .pdf (.25 MB) Help with pdf files Multimedia component 3 A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statementJournal of HepatologyVol. 73Issue 1PreviewThe exclusion of other chronic liver diseases including “excess” alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, “positive criteria” to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. Full-Text PDF