The Relationship Between Weight Change Across Adulthood And The Risk And Mortality Of Metabolic Dysfunction-associated Fatty Liver Disease

Backgroud and ObjectiveMetabolic dysfunction-associated fatty liver disease(MAFLD)is a new concept proposed by an international expert group in 2020,and now it is the leading cause of chronic liver disease worldwide.The primary treatment for MAFLD remains weight loss through lifestyle interventions or medications or surgery,as to alleviate intrahepatic steatosis and reduce complications.However,the relationship between weight change and the prevalence and long-term outcome of MAFLD is unclear.We are aimming to explore the relationship between weight change across adulthood and the risk and mortality of MAFLD,for providing a reliable theoretical basis for clinical decision making.MethodsWe analyzed data from 7,354 participants with over 25 years of follow-up data in The Third National Health and Nutrition Examination Survey.Three time intervals of adulthood were defined with different time points combination:age 25 to 10 years prior to baseline was defined as early to middle adulthood;age 25 to baseline was defined as early to late adulthood;10 years prior to baseline to baseline was defined as middle to late adulthood.Five weight change patterns were determined according to the BMI changes in the three time intervals as follows:stable normal(<25.0 kg/m2,before and later),stable overweight(25.0-29.9 kg/m2,before and later),stable obesity(≥30.0 kg/m2,before and later),weight loss(≥25.0 kg/m2 before and<25.0 kg/m2 later),and weight gain(<25.0 kg/m2 before and ≥25.0 kg/m2 later).The participants were assessed as fatty liver with liver ultrasound and diagnosed as MAFLD according to the data and guidelines.In the first part,"Exploring the relationship between different patterns of weight change across adulthood and the risk of MAFLD",weighted logistic regression analysis was used to analyse the association between different weight change patterns and the risk of MAFLD.In addition,subgroup analysis was used to evaluate the stability of the result.In the second part,"Exploring the relationship between different patterns of weight change across adulthood and the mortality in MAFLD patients",two classifications of weight change patterns were created,and weighted Cox proportional regression model was performed to assess the hazard ratios of all-cause mortality and heart disease mortality in the three time intervals for patients with MAFLD.ResultsIn the first part,using the stable normal group as a reference,weight loss group had a 1.23-fold increased risk of MAFLD(odds ratio[OR]:2.23,95%CI:1.07-4.65)from early adulthood to middle adulthood after adjusting for the confounding factors,while the stable obese group had a significant 6.47-fold increased risk(OR:7.47,95%CI:4.08-13.66).Subgroup analysis suggested stability of the above conclusions.In particularly,participants who never engage in physical activity among stable obese individuals have a significantly higher risk of MAFLD than those who engage in physical activity.Among the subgroup that never engages in physical activity in stable obese individuals,the risk of MAFLD from early to middle adulthood increased by 14.05 folds(OR:15.05,95%CI:5.03-45.02),while the corresponding subgroup engaging in physical activity only increased by 5.16 folds(OR:6.16,95%CI:3.0212.59).Similar results were observed for the other two time intervals.In the second part,patients with MAFLD who gained between 10 and 20 kg from early adulthood to middle adulthood had a 93%increased risk of all-cause mortality(HR:1.93,95%CI:1.30-2.88)after adjusting for the confounding factors,while those who gained more than 20 kg had a 78%increased risk of all-cause mortality(HR:1.78,95%CI:1.03-3.09).The stable obese group showed a 3.08-fold higher risk of heart disease mortality(HR:4.08,95%CI:1.35-12.32).Conclusions1.In this prospective cross-sectional study,people with stable normal weight and weight loss in adulthood had the lower risk of MAFLD,while stable obese people had a significantly higher risk of MAFLD,especially in those who never performed physical activity;2.Individuals with weight gain from early adulthood to middle adulthood were prone to increased all-cause mortality risks of MAFLD,whereas individuals with stable obesity across adulthood had a higher heart disease mortality risk.