Quantitative Hepatitis B Core Antibody Levels In The Different Stages Of Chronic Hepatitis B Virus Infection

Objective To investigate the dynamic changes and clinical significance of quantitative hepatitis B core antibody(HBcAb)in different stages of chronic hepatitis B virus(HBV)infection.Methods A total of 194 patients with chronic HBV infection from November 2018to August 2019 were enrolled,and they were divided into Immune tolerant phase(n=22),Immune clearance phase(CHB)group(n=68),Low-replicative phase(n=41),and HBe Ag-negative hepatitis(n=23).A total of 16 patients with compensated cirrhosis,15patients with decompensated cirrhosis and 9 patients with hepatocellular carcinoma were included too.The general conditions data were collected,and hepatitis B core antibody(HBc Ab),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),hepatitis B virus load(HBV DNA),total bilirubin(TBIL),albumin(ALB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),?-glutamyl transferase(GGT),alkaline phosphatase(ALP),alpha-fetoprotein(AFP),prothrombin time(PT),Prothrombin activity(PTA),international standardized ratio(INR),white blood cell count(WBC),hemoglobin(Hb),platelet(PLT)and CD4 cell count were detected.The dynamic changes in different stages of chronic hepatitis B virus infection was analyzed,and the associations between HBc Ab level and clinical parameters were analyzed.Results1.The median levels of HBc Ab in different stages of chronic HBV infection were as following:Immune tolerant phase(HBeAg-positive chronic HBV infection)2.16lgIU/mL,Immune clearance phase(HBe Ag-positive CHB)2.77 lgIU/mL,Low-replicative phase(HBeAg-negative chronic HBV infection)2.62 lgIU/mL,HBe Ag-negative hepatitis(HBeAg-negative CHB)3.19 lgIU/mL,compensated cirrhosis group 3.0 lgIU/mL,decompensated cirrhosis group 3.69 lgIU/mL,and hepatocellular carcinoma group 2.25 lgIU/m L.HBc Ab levels in Immune clearance phase and HBe Ag-negative hepatitis were significantly higher than Immune tolerant phase and Low-replicative phase(p<0.01).2.There was a significant difference in PLT levels around in different natural history(p<0.01).PLT levels from high to low in order were as Immune tolerant phase,Low-replicative phase,HBeAg-negative hepatitis and Immune clearance phase.After multiple comparisons,we found that there are statistically significant differences in PLT levels between Immune tolerant phase and Immune clearance phase(p<0.01),Immune clearance phase and Immune clearance phase(p<0.05).In addition,the average level of PLT in chronic HBV infection and HBV-related cirrhosis and liver cancer was188×10~9/L and 113×10~9/L(p<0.01).3.In the natural history,the HBcAb was significant related to ALT(r=0.521,p<0.001)and AST(r=0.504,p<0.001);and it had low correlation with GGT(r=0.39,p<0.001),and had weak correlation with AFP(r=0.292,p<0.001),PTA(r=0.187,p<0.001),PLT(r=0.257,p<0.001).4.In HBe Ag-positive patients,the AUROC of HBcAb used to distinguish HBe Ag-positive chronic HBV infection from HBeAg-positive CHB was 0.930(95%CI:0.871?0.988,p<0.001).The Youden index is 0.734,and he cut-off value of 2.57 log10 IU/m L for HBeAg-positive CHB had a sensitivity of 77.9%,specificity of 95.5%.On the other hand,the AUROC of HBc Ab used to distinguish HBeAg-negative chronic HBV infection from HBe Ag-negative CHB was 0.840(95%CI:0.729?0.951,p<0.001)in HBe Ag-negative patients,.The Youden index is 0.628,and he cut-off value of 2.98 log10 IU/mL for HBe Ag-negative CHB had a sensitivity of 65.2%,specificity of 97.6%.Conclusion1.Serum HBc Ab level varied in different natural history phases of HBV infection.HBcAb levels in Immune clearance phase and HBeAg-negative hepatitis were significantly higher than Immune tolerant phase and Low-replicative phase.2.Serum PLT level varied in different natural history phases of HBV infection.PLT levels in Immune clearance phase were significantly lower than Immune tolerant phase.3.Serum the HBcAb was positively associated with ALT and AST.Serum HBcAb level could be used to distinguish the natural history statue of chronic HBV infection.4.Serum HBcAb level is strongly associated with host's immune status and hepatitis activity in subjects with chronic HBV infection.