Correlation Between Indicators Of Immune And Non-alcoholic Fatty Liver Disease In Obese Children

BackgroundWith the increasing incidence of obesity,the complications of obesity are rising,such as non-alcoholic fatty liver disease(NAFLD).NAFLD is a kind of hepatic steatosis,inflammation and fibrosis,which characterized by fatty infiltration of the liver hepatocytes>5%,except for the history of alcohol intake and viral infections,autoimmune hepatitis and drug-induced liver disease.With the progress of NAFLD,it is likely to develope into liver fibrosis and cirrhosis,and even liver cancer,which threatended human health seriously.According to pathologic changes in liver tissue classification and whether the lesions associated with inflammation and fibrosis,NAFLD divided into simple fatty liver(SFL),non-alcoholic steatohepatitis(NASH)and associated cirrhosis.At present,the pathogenesis of NAFLD is still not fully undertood,it has been reported that immunity cells and cytokines may be involved.Currently,a small amout studies have been reported on relationship between indicatorsof immune and NAFLD in children.ObjectiveTo investigate the relationship between immune indicators(peripheral blood cell count and cytokines)and NAFLD,also the risk fators for NAFLD,we measured the anthropometric indicators,parameters of glycometabolism,lipid metabolism and immune indicators(peripheral blood cell count and cytokines)in obese children.MethodsA total of 117 obese children aged from 5.2 to 14.8 years(10.81±2.2 years)were enrolled as obese group during July 2015 to September 2015,who hospitalized in Endocrinology Department of Children's Hospital of Zhejiang University School of Medicine.They included 81 males and 36 females.Their body mass index(BMI)ranged from 22.2 kg/m2 to 42.2 kg/m2(28.48±3.76 kg/m2).Other 209 no-obese children aged from 6.0 to 14.0 years(10.29± 1.79 years),including 149 males and 60 females,were enrolled as control group.Their BMI ranged from 11.6 kg/m2 to 22.3 kg/m2(15.65±1.86 kg/m2).Difference of gender between obese group and control group was not significant(P<0.05)while the difference of age was significantly(P<0.05).Depending on the severity of NAFLD,Obese group divided into three subgroups:simple obese group(without NAFLD image features by US examination and normal liver alanine aminotransferase,n=23),NAFLD group(with NAFLD image features by US examination and normal ALT,n=43)and NASH group(with NAFLD image features by US examination and elevated ALT,n=51).Simple obese group aged from 5.8 to 14.0 years(9.8±2.5 years)included 14 males and 9 females.Their BMI ranged from 22.4 kg/m2 to 32.0 kg/m2(26.1 ±2.5 kg/m2).NAFLD group aged 5.2 to 14.2 years(10.8±2.2 years)included 30 males and 13 females.Their BMI ranged from 22.2 kg/m2 to 34.9 kg/m2(28.2±3.1 kg/m2).NASH group aged 5.9 to 14.8 years(11.3±1.9 years)included 37 males and 14 females.Their BMI ranged from 22.5 kg/m2 to 42.2 kg/m2(29.7±4.2 kg/m2).These was no significant difference of gender among three subgroups(P<0.05)while difference of age was statistically significant(P<0.05).Physical examination,routine blood test,blood biochemical test and cytokines detection,including body height,body weight,waist circumference(WC),hip circumference(HC),fasting blood glucose(FBG),fasting insulin(FINS),triglyceride(TG),total cholesterol(TC),lipoprotein a(Lpa),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),apolipoprotein(Apo)B,ApoAl,alanime aminotransferase(ALT),aspartate aminotransferase(AST),uric acid(UA),white blood cell(WBC),neutrophil%(N%),lymphocyte%(L%),platelet(PLT),interleukin(IL)-2,IL-4,IL-6,IL-10,tumor necrosis factor-alpha(TNF)-?,interferon(IFN)-? were measured.Ultrasound examination(US)for liver was performed.Body mass index(BMI),ApoB/ApoA1,homeostatic model assessment-insulin resistance(HOMA-IR)were calculated.The differences of each indicators between obese group and control were compared,and three subgroups were also compared.Spearman correlation analysis was performed,we used each indicators as the independent variables,NAFLD status as a dependent variable(the control group,simple obese group,NAFLD group and NASH group were assigned 1,2,3 and 4 respectively).Then logistic regression analysis was performed to analyze the independent factors of NAFLD.ResultIn the obese group,BMI,WC and HC were significantly higher than those in the controls(P<0.05,respectively).Among the 117 obese children,NAFLD was found in 94(80.3%).BMI,WC,HC were significantly different among simple obese group,NAFLD group and NASH group(P<0.05,respectively).BMI,WC and HC in NASH group were higher than those in simple obese group(P<0.05,respectively).BMI and WC in NAFLD group were higher than those in simple obese group(P<0.05,respectively).BMI in NASH group was higher than that in NAFLD group(P<0.05).HC in NASH group was higher than that in simple obese group(P<0.05).Compared to the control group,FINS and HOMA-IR were significantly higher in the obese group(P<0.05,respectively).FBG was not significantly different between the obese and control groups(P>0.05).FINS and HOMA-IR were significantly different among simple obese group,NAFLD group and NASH group(P<0.05,respectively).FINS and HOMA-IR in NASH group were higher than those in simple obese group(P<0.05,respectively).FBG was not significantly different among three subgroups(P>0.05).In the obese group,TG,TC,LDL-C and ApoB/ApoAl were significantly higher than those in the controls(P<0.05,respectively)while HDL-C was significantly lower than that in the controls(P<0.05).Lpa was not significantly different between the obese and control groups(P>0.05).There was no significant difference of TG,TC,HDL-C,LDL-C,Lpa and ApoB/ApoA1 among simple obese group,NAFLD group and NASH group(P>0.05,respectively).Compared to the control group,ALT and UA were significantly higher in the obese group(P<0.05,respectively).AST was not significantly different between the obese and control groups(P>0.05).ALT,AST and UA were significantly different among simple obese group,NAFLD group and NASH group(P<0.05,respectively).ALT,AST and UA in NASH group were higher than those in simple obese group and NAFLD group(P<0.05,respectively).In the obese group,WBC,N%,PLT and IL-6 were significantly higher than those in the controls(P<0.05,respectively)while L%was significantly lower than that in the controls(P<0.05),IL-2,IL-4,IL-10,TNF-? and IFN-? were not significantly different between the obese and control groups(P>0.05,respectively).IL-6 and IL-10 were significantly different among simple obese group,NAFLD group and NASH group(P<0.05,respectively).IL-6 in NASH group was higher than that in simple obese group(P<0.05).IL-10 in NASH group was higher than that in simple obese group and NAFLD group(P<0.05).WBC,N%,L%,PLT,IL-2,IL-4,TNF-a and IFN-y were notsignificantly different among three subgroups(P>0.05,respectively).Correlation analysis showed that NAFLD significantly positively correlated with age,BMI,WC,HC,ALT,AST,UA,TG,TC,LDL-C,ApoB/ApoA1,FINS,HOMA-IR,IL-6,IL-10,WBC,N%and PLT(P<0.05,respectively),but negatively correlated with HDL-L and L%(P<0.05,respectively).The logistic regression analysis showed that BMI,LDL-C,HOMA-IR and IL-10 were independent determinants for NAFLD(P<0.05,respectively).Conclusion1.Low-grade chronic inflammation in obse childrendemonstrate.2.A close correlation between childhood obesity and NAFLD.3.BMI,LDL-C,HOMA-IR and IL-10 are independent factors for NAFLD in children.Moreover,obesity,dyslipidaemia and IR are risk factors while IL-10 may be a protective factor for NAFLD.