The Study Of Serum Acid Sphingomyelinase Expression And Its Significance In Patients With Nonalcoholic Fatty Liver Disease

Aim Recent studies have shown that serum acid sphingomyelinase(ASMase)plays a crucial role in the development of non-alcoholic fatty liver disease(NAFLD).This study determined the serum ASMase expression in patients with NAFLD,analyzed the relationship between ASMase and NAFLD steatosis and related fibrosis,preliminary revealed the possible mechanism of ASMase involved in the occurrence and development of NAFLD,and initially discussed ASMase as a diagnosis of NAFLD,predicting the degree of NAFLD steatosis and the possibility and value of related fibrotic biomarkers.Methods This study was a case-control study,and was approved by the Ethics Committee of the First Affiliated Hospital of Xi’an Medical University.A total of 120 subjects were enrolled in this study,among them,90 patients who were diagnosed as NAFLD at the First Affiliated Hospital of Xi’an Medical University from June 2017 to October 2017 were classified as case group,and 30 health examiners were classified as control group.All subjects were informed of the purpose of the study and signed written informed consent.A total of 120 subjects were included in the study.There were 90 patients with NAFLD in the case group,55 males and 35 females.The age range was between 21 and 69 years,with an average of 42.5±12.9 years.In the control group,there were 30 healthy persons,14 males and 16 females.The age range was between 21 and 69 years,with an average age of 47.3±11.0 years.With reference to the diagnostic criteria of NAFLD of the Chinese Medical Association Liver Diseases Branch in 2010,two-dimensional real-time ultrasound of the abdomen was used to diagnose NAFLD and its degree of steatosis.Assessment of NAFLD-associated fibrosis uses the FibroScan and FIB-4 index.Ergonomic parameters of each subject was collected,peripheral fasting blood and centrifugation were collected in the early morning and used for the determination of related hematological and serological parameters(analysis of automatic hematology analyzer,automatic biochemical analyzer analysis),white blood cells(WBC),platelet(PLT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl transpeptidase(GGT),uric acid(UA),creatinine(CREA),urea nitrogen(UREA),triglyceride(TG),cholesterol(CHOL),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C),fasting plasma glucose(FPG),free fatty acids(FFA),glycated hemoglobin(HbA1c),albumin(ALB),fasting insulin(FINS),and ASMase level(ELISA),respectively.Calculate the homeostatic model assessment-insulin resistance index and FIB-4 index.All of the resulting data was analyzed using SPSS 18.0 software.All variables were expressed as mean±SD.The Kolmogorov-Smirnov test was used to assess whether the continuous variables were normally distributed.Differences between groups of continuous variables were compared using t-test or Mann-Whitney U test.Categorical variables or count variables use chi-square test to compare differences.one-way ANOVA for comparing of multiple samples.Pearson test or Spearman test for correlation analysis.The diagnostic effect of ASMase was evaluated using a receiver operating characteristic curve(ROC).P < 0.05 was considered statistically significant.Charts were created using Excel 2003 and Graphpad Prism 6.0,Medcalc software.Results 1.Serum ASMase levels in NAFLD patients(25.8±3.5 nmol/L)were significantly higher than those in the control group(22.6±2.2 nmol/L)(P<0.01).According to the sonographic results of the subgroup of case components,the three groups showed a statistically significant difference(P<0.01).Then the comparison between groups(control group and mild NAFLD group,control group and moderate-severe NAFLD group,mild NAFLD group and moderate-severe group)showed that the difference was statistically significant(P<0.01).It is suggested that the level of ASMase is related to the degree of steatosis of NAFLD,and the level of serum ASMase gradually increases as the degree of steatosis increases.2.HOMA-IR(r=0.210,P<0.05),AST(r=0.247,P<0.05),BMI(r=0.252,P<0.05),LSM(r=0.276,P<0.01),HbA1c(r=0.230,P<0.05)were all positively correlated with ASMase,WBC(r=-0.304,P<0.01),CHOL(r=-0.234,P<0.05),LDL-C(r=-0.211,P<0.05)were all negatively correlated with ASMase.3.The assessment of NAFLD-related fibrosis was based on Liver Stiffness Measurement(LSM)and FIB-4 index determined by FibroScan.The case group was divided into three subgroups and the difference between the three groups was statistically significant(P<0.01,P<0.05),suggesting that ASMase is associated with NAFLD-related fibrosis and increases with the progression of fibrosis.4.For the diagnosis of NAFLD,the area under the curve of ASMase(AUC)= 0.701(P <0.01),suggesting that ASMase as an independent marker has a certain accuracy in the diagnosis of NAFLD.For the diagnosis of NAFLD-related fibrosis(LSM diagnosis),AUC=0.701(P<0.01)by F2 and AUC=0.858(P<0.01)by F3,suggesting that ASMase acts as an independent marker for NAFLD-related fibrosis(F3 Above)has a certain diagnostic efficiency.Conclusions 1.The level of serum ASMase in NAFLD patients was significantly higher than that in the control group,and the expression was up-regulated,which was correlated with HOMR-IR.It suggested that ASMase was associated with insulin resistance(IR)and increased with the increase of IR;ASMase may pass insulin signal The pathway up-regulates IR,thereby affecting lipid metabolism in liver cells,leading to liver steatosis,inflammation,and fibrosis;2.ASMase is associated with the degree of steatosis and associated fibrosis in NAFLD and increases with the progression of steatosis and fibrosis,suggesting that ASMase is involved in the development of NAFLD steatosis and fibrosis;3.ASMase may be an important factor involved in the pathogenesis of NAFLD.ROC curve analysis suggests that ASMase can be used as an independent marker to diagnose NAFLD.Assessment of NAFLD-related changes in fibrosis,especially F3 or more,has a certain diagnostic effect,while duing to the small number of samples in this experiment,further basic research and large sample clinical studies may be needed to verify or jointly diagnose with other indicators.