Clinical Characteristics And Long-term Outcomes Of Metabolic Dysfunction-Associated Fatty Liver Disease In Pediatric Population

Background and Aims:Fatty liver disease(FLD)is one of the most common chronic non-communicable liver diseases around the world.In 2020,a panel of international hepatologists suggested to rename non-alcoholic fatty liver disease(NAFLD)as metabolic dysfunction-associated fatty liver disease(MAFLD)and introduced a set of positive diagnostic criteria.However,most studies are limited to adult cohort evaluated by non-invasive methods and have not been extensively validated in pediatric population.Meanwhile,as one of the most common chronic liver diseases in China,chronic hepatitis B(CHB)is usually concomitant with MAFLD.There are still controversies over the impact of the interaction between CHB and MAFLD on the progression and outcomes of liver disease,especially in children.Therefore,our aim was to investigate the differences between MAFLD and NAFLD on the disease severity and clinical outcomes in a biopsy-proven pediatric cohort.We also analyzed the clinical characteristics of CHB concomitant with MAFLD in children and explored the effect of CHB concomitant with MAFLD on the progression of liver disease.Methods:370 children(≤18 years)with biopsy-proven fatty liver between January 2010 and December 2021 were consecutively enrooled from electronic medical records and categorized into 3 distinct subgroups of MAFLD-only,NAFLD-only and MAFLD-NAFLD according to the diagnostic status.Differences in demographic data,clinical manifestations and results of laboratory tests between MAFLD and NAFLD were compared and adverse clinical outcomes were follow-up.The end point of follow-up was June 2022.Children with CHB-MAFLD were selected for this study.Children with simple-CHB and simple-MAFLD were also extracted as the control group in the study.We used propensity score matching(PSM)to balance baseline age and sex between the groups.Multivariate logistic regression was applied to analyze the risk factors for significant fibrosis.Results:1.Children with MAFLD-only and MAFLD-NAFLD had more features of metabolic disorders,with higher level of BMI and TG than NAFLD-only.The proportion of significant fibrosis(stage>2)was highest in MAFLD-only(69.6%),followed by those with MAFLD-NAFLD and NAFLD-only(46.4%and 21.3%,respectively;P<0.001).More steatohepatitis was presented in MAFLD-NAFLD group than the other two groups(69.6%vs 33.0%vs 32.8%,P<0.001).Multivariate regression revealed that patients with MAFLD-only had 6.7-fold greater risk of significant fibrosis compared with NAFLD-only(OR 6.754,95%CI:3.048-14.967,P<0.001).After a median follow-up of 81 months,13 of 370 patients developed clinical events.Survival curves indicated no statistically significant difference in the cumulative incidence of clinical events between the MAFLD-only and NAFLD-only groups(Log-Rank test,P=0.252).2.In the cohort of CHB,the CHB-MAFLD group had a higher level of BMI,TG and TC but low level of ALT and AST than the simple-CHB group(P<0.05).Notably,the degree of fibrosis was more severe in the CHB-MAFLD group(67.9%vs 49.1%,P=0.021).Multivariate logistic regression results showed that high-risk indicators,such as BMI(OR 1.258,P=0.001)and TG(OR 12.334,P<0.001)were independently contributed to hepatic steatosis.Significant fibrosis was closely associated with hepatic steatosis(OR 4.104,P=0.002).3.In the cohort of MAFLD,the CHB-MAFLD group had a lower level of BMI,TG,ALT and GGT compared with simple-MAFLD group.Despite the degree of hepatic steatosis in CHB-MAFLD group were milder than those in simple-MAFLD group,the degree of fibrosis was more severe in simple-MAFLD group(P=0.021).No significant difference in the activity of inflammatory between the two groups(P=0.512).Multivariate analysis showed that chronic HBV infection was negatively associated with severe hepatocyte lipidosis(OR 0.203,P<0.001)and independently positive associated with severe fibrosis(OR 2.708,P=0.011).Conclusions:1.Patients with MAFLD tended to have more worse metabolic diseases and severe fibrosis compared to those with NAFLD-only in the pediatric cohort.Thus,the redefinition of MAFLD may improve the detection of children with significant diseases that need early intervention.2.In children with CHB,metabolic dysfunction played a very important role in the development of MAFLD.There was negative association between HBV infection and the degree of liver steatosis.Furthermore,MAFLD concomitant CHB may promote the progression of liver fibrosis.