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Objective:To establish and evaluate a new diagnostic model for significant liver tissue damage in patients with chronic hepatitis B virus (HBV) infection in the immune tolerance phase.Methods:The clinical data of 275 chronic HBV infection patients in the immune tolerance phase who underwent liver biopsy from January 2015 to November 2020 in the Hwa Mei Hospital, University of Chinese Academy of Sciences were included. According to the liver pathological changes, patients were divided into <G2 group and ≥G2 group, <S2 group and ≥S2 group, non-significant liver pathological damage group (GS0 group, <G2+ <S2) and significant liver pathological damage group (GS1 group, G2 and/or ≥S2). The liver pathological changes and clinical features were analyzed to establish the diagnostic model. The prediction value of the model was compared. Statistical analysis was conducted by linear regression analysis, and the area under the receiver operating characteristic curve, sensitivity and specificity for the diagnostic value of the model were calculated.Results:Among 275 patients, 43 cases (15.64%) had liver histologic activity ≥G2, 30 cases (10.91%) with liver fibrosis ≥S2, and 55 cases (20.00%) with liver damage of GS1. The correlated independent risk factors associated with significant liver pathological damage were age, levels of hepatitis B e antigen, γ-glutamyl transpeptidase, platelet count, alkaline phosphatase and alanine aminotransferase (all P<0.050). The diagnostic model of Y G/S was established according to these factors. The diagnostic efficacy of Y G/Swas highest for patients with liver histologic activity≥G2 and liver pathological damage GS1, with the areas under the curve of 0.783 and 0.811, respectively. The threshold of Y G/S was 0.18, with the sensitivity, specificity and negative predictive value of 0.782, 0.736 and 93.10%, respectively. When Y G/S <0.05, the sensitivity, negative predictive value and negative likelihood ratio were 0.982, 97.96% and 0.08, respectively. When Y G/S≥0.25, the specificity and positive likelihood ratio were 0.905 and 5.14, respectively. When Y G/S≥0.30, the specificity and positive likelihood ratio were 0.959 and 9.33, respectively. Conclusions:Approximately 20.00% of patients with chronic HBV infection in immune tolerance phase have significant liver pathological damage. The diagnostic model of Y G/S (<0.05 or ≥0.30) has certain evaluation value for significant liver pathological damage, and could help these patients avoid liver biopsy to a certain extent.
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This article discusses the definition of the indeterminate phase of chronic hepatitis B and summarizes the proportion of patients in the indeterminate phase of chronic hepatitis B among patients with chronic HBV infection, as well as their risk of hepatocellular carcinoma and related treatment recommendations.
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Objective To analyze the change of intrahepatic regulatory T cells (Treg )/helper thymphorytes (Th)17 balance in patients with different phases of chronic hepatitis B virus (HBV ) infection ,and to explore the role of Treg/Th17 balance in maintaining immune tolerance and inducing immune clearance ,and its influence on disease progression .Methods Sixty-eight patients with chronic HBV infection who underwent liver biopsy in Tianjin Second People′s Hospital were included .The 68 patients included 20 cases in immune tolerant (IT) phase ,36 cases in immune clearance (IC) phase and 12 cases in inactive phase .Eight healthy liver transplant donors were collected as healthy controls .The intrahepatic Treg/Th17 levels were detected by immuno-histochemical method . The changes of Treg/Th17 balance in patients with different phases of chronic HBV infection ,and the relationship between Treg/Th17 balance and the decreases of hepatitis B surface antigen (HBsAg ) , hepatitis B antigen (HBeAg) and HBV DNA levels in the peripheral blood were analyzed in patients with IC phase at two weeks of admission .Results The intrahepatic Treg and Th17 levels in IC phase group were the highest , then and they were higher in inactive phase group were higher than those in IT phase group ,And they were the lowest in control group .The Treg level in IC phase group increased significantly compared with the other three groups (all P< 0 .01) ,and there were no significant differences among the other three groups (all P> 0 .05) .The Th17 level between IT phase group and inactive phase group was not significantly different (P> 0 .05) ,while the differences were not significant in other groups (all P>0 .05) .Treg/Th17 ratio of IT phase group was the highest ,then the ratio of control group was higher than that of inactive phase group ,and IC phase group was the lowest ratio .The differences between IC phase group ,control group and IT phase group were significant (all P< 0 .05) ,and the difference between inactive phase group and IT phase group was also significant (all P<0 .05);and there was no significant difference among other groups (all P>0 .05) .The decreases of HBsAg ,HBeAg and HBV DNA levels in the peripheral blood at two weeks admission were negatively correlated with the intrahepatic Treg cell level in patients in IC phase of chronic HBV infection ( r= -0 .941 ,-0 .869 ,and -0 .883 ,respectively ,both P<0 .01) .The Treg ,Th17 levels and their ratio in IC phase group with different degree of inflammation and fibrosis had significant differences :G4 group > G3 group > G2 group ,S3 group > S2 group > S1 group (all P<0 .05) .Conclusions There is no change of the Treg/Th17 balance in IT phase ,and Treg has no influence on maintaining immune tolerance in chronic HBV infection .T he imbalance of Treg/Th17 is observed in IC phase .Th17 may actively participate in the immune-mediated liver injury and the development of hepatic fibrosis in CHB patients .Treg may inhibit inflammation and reduce liver injury via the negative feedback regulation mechanism ,and may impede the eradication of HBV simultaneously .