Association Between New Clinical Clusters Of MAFLD And Prognosis Based On Monocyte/Lymphocyte Ratio

BackgroundMetabolic associated fatty liver disease(MAFLD)is the most common chronic liver disease,affecting 20-30%of the adults throughout the world.And the incidence of MAFLD is increasing year by year,which brings a huge challenge to the medical system of all countries.MAFLD is associated with increased risk of liver cirrhosis,hepatocellular carcinoma,type 2 diabetes mellitus(T2DM)and atherosclerosis.However,there is no effective therapy to delay the progression of MAFLD and the occurrence of related complications.In the United States,MAFLD has been associated with increased all-cause mortality.It has been shown that approximately half of deaths in patients with MAFLD are related to complications such as T2DM and atherosclerosis.In addition,disease progression in the MAFLD population is highly heterogeneous,and the current simple dichotomies of MAFLD(simple hepatic steatosis and steatohepatitis)are not helpful for the diagnosis and management of the large MAFLD population.However,at present,the risk indicators of MAFLD are not so clear yet.Therefore,it is of great significance to explore the risk indicators of MAFLD in individuals.And establishing a classification that could comprehensively identify and predict the subtype with high risk of intra-and extra-hepatic complications of MAFLD is essential for the management and precise treatment of MAFLD population.MethodsThis study used prospective cohort data from the UK Biobank and participants with MAFLD were determined by combining fatty liver index(FLI)and metabolic risk factors.The outcome events were intra-and extra-hepatic complications(severe liver disease(SLD),end-stage renal disease(ERSD),stroke,heart failure,coronary heart disease(CAD),diabetes).Logistic regression was used to analyze the relationship between variables and MAFLD and MAFLD-related fibrosis and the odd ratio(OR)and 95%confidence interval(95%CI)were calculated.Participant cluster analysis was performed using the K-means clustering tool.Cox proportional hazard regression model was used to analyze the relationship between variables and incidence of MAFLD-related intra-and extra-hepatic complications,and hazard ratio(HR)and 95%CI were calculated.ResultIn cross-sectional population of MAFLD,monocyte/lymphocyte ratio(MLR)was independently and positively associated with MAFLD in the univariate and multivariate logistic analyses[model 1 OR(95%CI)3.13(2.93,3.34);model 4 OR(95%CI)2.00(1.74,2.30)].Univariate and multivariate Cox regression analyses further identified elevated MLR as an independent risk factor for the incidence of SLD in MAFLD population[high MLR vs.low MLR HR(95%CI)1.56(1.32,1.85);intermediate MLR vs.low MLR HR(95%CI)1.13(0.95,1.35)].Furthermore,MLR and another 6 continuous variables were selected as clustering features via correlation analysis with Fibrosis-4 Index(FIB-4),and the MAFLD participants were divided into 5 different subtypes using K-means clustering tool,which are HL-MD,AR-MD,HB-MD,HM-MD and HA-MD.What’s more,the incidence of MAFLD-related SLD and type 2 diabetes of HA-MD was higher than that of the other four subtypes,and HM-MD was a high-risk group for ESRD,stroke,heart failure and CAD.ConclusionThis study found that elevated inflammatory index,MLR was an independent risk factor for MAFLD and its related liver fibrosis and SLD.Furthermore,a cluster model based on MLR combined with other 6 clinical indicators was established to identify subtypes at high risk of intrahepatic and extrahepatic complications,providing significant instruction for the management and individualized treatment of MAFLD participants.