The Study Of Pathological Features Of The Inflammation And Noninvasive Clinical Model Among The Chronic HBV Infection Combined With Nonalcoholic Fatty Liver Disease

Objective:To distinguish the reason of liver inflammation through the observation of pathological features in patients among the chronic HBV infection combined with nonalcoholic fatty liver disease,compare the clinical characteristics between them,analysis index related with the inflammation,and investigate whether there is a noninvasive method such as formula to identify the causes of inflammation,thus we can establish a noninvasive diagnostic model to chronic HBV(Hepatitis B Virus,HBV)infection with nonalcoholic fatty liver disease(NAFLD).Methods:Collect the patients of chronic HBV infection complicated with nonalcoholic fatty liver disease from January 2014 to December 2016 in Tianjin Second People's Hospital.Firstly,we observed the pathological features of the liver,and analysis the causes of the liver inflammation.Then,according to the different pathological characteristics,divided the patients mainly into HBV inflammation group(the inflammatory activity that had actively infected with HBV in chronic HBV infection combined with NAFLD patients)and non-HBV inflammation group(there was no HBV related inflammatory activity of chronic HBV infection combined with NAFLD patients)in pathological tissues by the pathological experts.Secondly,we compared the the difference of two groups in general characteristics and clinical data(including liver and kidney function,blood lipids,blood glucose,uric acid,insulin,five items of hepatitis B,HBV-DNA,thyroid function,anemia four,immune function,blood routine,ultrasound,CAP,FibroScan)through the single factor analysis.Thirdly,according to the two logistic regression analysis the indexes of clinical differences,we got the correlation indexes with the liver inflammation and a regression formula.Then,to verify its accuracy evaluation of the regression formula.Results:1.Pathological manifestations in the HBV inflammation group: the portal area were expanded,main mononuclear inflammatory cells infiltrated the portal area,or lymphocytes aggregatively infiltrated,and interfacial inflammation.Pathologicalmanifestations in the non-HBV inflammation group: expanded portal area and infiltration of inflammatory cells in the portal area were not obvious,and no interfacial inflammation.2.The average age of the patients in the HBV inflammation group(41.8±9.9years)was higher than the non-HBV inflammation group(36.42±10.49 years),there was a statistically significant difference between them(P<0.05).There was no significant difference between the two groups in gender and body mass index(BMI)(all P>0.05).In the HBV inflammation group,the inflammation was significantly more serious than that in the non-HBV inflammation group,but,the degree of hepatic steatosis was lighter than that of non-active HBV group,the differences between them were statistically significant(all P<0.05).3.The level of ALT,AST,GGT,ALP in the HBV inflammation group were higher than those in the non-HBV inflammation group,the differences were statistically significant(all P<0.05).The level of TP,ALB and UA in the HBV inflammation group were lower than those in the non-HBV inflammation group,and the differences were statistically significant(all P<0.05).The level of TBIL,BUN,CRE,TG,CHO,HDL and LDL in two groups had no significant differences(all P>0.05).4.There were no statistically significant difference in the level of HBsAg,HBeAg,HBeAg positive rate,TT3,TT4,FT3,FT4,TSH,TGAB and insulin between the two groups(all P>0.05).The HBV-DNA quantification in HBV inflammation group was higher than that in non-HBV inflammation group,the difference was statistically significant(P<0.05).5.The level of complement C3 in HBV inflammation group is lower than that in the non-HBV inflammation group,the difference was statistically significant(P<0.05),and the level of complement C4,IgG,IgA,IgM,TFR,Fe,FER,TIBC and UIBC had no difference between the two group,the difference was not statistically significant(all P>0.05).6.The level of WBC,NEUT and PLT in patients with HBV inflammation group were lower than those in non-HBV inflammation group,the differences were statistically significant(all P<0.05).The level of MPV and MCV were higher thanthose in non-HBV inflammation group,the difference were statistically significant(all P<0.05).The level of LYMPH,RBC,HGB,HCT were not different,the difference were not statistically significant(all P>0.05).7.The CAP value of the HBV inflammation group was lower than that of the non-HBV inflammation group,and the liver stiffness measurement(E)was higher than that of the non-HBV inflammation group,the differences were statistically significant(all P<0.05).8.Stepwise logistic regression analysis,there was statistical significance difference in four factors of age,CAP,E,ALT(all P <0.05),the regression equation was Y=0.106*age-0.033*CAP+0.48*E+0.048*ALT-0.86,the overall rate of correct prediction was 83.1%.The corresponding AUC was 0.922,P<0.001,and the cut-off value was 0.534.The sensitivity,specificity,positive predictive value,and negative predictive value were 80%,90.91%,93.6%,73.2%,respectively.9.The accuracy rate of the formula Y=0.106*age-0.033*CAP+0.48*E+0.048*ALT-0.86 in the validation group was 63.64%.However,the patients who w ere diagnosed as the HBV inflammation group through the formula(Y>0.534)were consistent with the pathological results,the coincidence rate was 100%.Conclusions:1.The features with inflammatory activity that had actively infected with HBV in chronic HBV infection combined with NAFLD patients(the HBV inflammation group)were as following : the serological markers of HBV were positive,while immunohistochemistry of HBsAg,HBcAg,PreS1 Ag were positive at least one item;and the liver steatosis was accorded with the morphological characteristics of NAFLD;the portal area were expanded,main mononuclear inflammatory cells infiltrated the portal area,or lymphocytes aggregatively infiltrated,and at least mild interfacial inflammation.2.The features with no HBV related inflammatory activity of chronic HBV infection combined with NAFLD patients(the non-HBV inflammation group)were as following: the serological markers of HBV were positive,while immunohistochemistry of HBsAg,HBcAg,PreS1 Ag were positive at least one item;and the liver steatosis was accorded with the morphological characteristics ofNAFLD;expanded portal area and infiltration of inflammatory cells in the portal area were not obvious,and no interfacial inflammation.;except: a clear inflammation around the central vein,with or not stent collapsed around the central vein;ceroid of Kuffer cells in hepatic sinusoid was Deposited.The liver inflammation in chronic HBV infection with NAFLD patients was mostly caused by HBV infection.3.The patients in HBV inflammation group had older age,and liver inflammation and fibrosis were more obvious in pathological features compared with the non-HBV inflammation group.They often had higher levels of ALT,AST,GGT,ALP and viral load in clinical findings.And the FibroScan value is larger,the CAP value is smaller.In addition,the blood test of WBC,NEUT,PLT were lower and the MPV was higher than the non-HBV inflammation group.These simple indicators had a certain predictive significance in discrimination the causes of inflammation in chronic HBV infection with NAFLD patients.4.We could refer to the formula Y=0.106*age-0.033*CAP+0.48*E+0.048*ALT-0.86 to screen inflammation,if the value of Y was greater than 0.534,we could consider the liver inflammation associated with HBV infection inflammation and pay great attention to problem of hepatitis B.If necessary,we should give the patients antiviral therapy,the usefulness of this formula needs to be further verified.