| 【Objective】1 This study aimed to explore the role of HBs Ag/RT protein mutation and Anti-HBs subtype-nonspecificity in patients with simultaneous HBs Ag/Anti-HBs positivity,and to analyze the effect of patients with simultaneous HBs Ag/Anti-HBs positivity on vaccines.2 To investigate the epidemiological characteristics and clinical features of patients with simultaneous HBs Ag/Anti-HBs positivity,and to explore the effect of HBs Ag mutation on the outcome of chronic HBV infected patients with co-existence of HBs Ag and Anti-HBs.【Method】1 The mechanism of co-existence of HBs Ag and Anti-HBs and the effect of patients with simultaneous HBs Ag/Anti-HBs positivity on vaccinations.The serum of patients with simultaneous HBs Ag/Anti-HBs positivity(experimental group,Group I)were collected from May 2015 to December 2015 at the First Affiliated Hostipal of Fujian Medical University.At the same time,chronic HBV infections with negative Anti-HBs whose age and sex were matched with Group I were served as a control group(Group II).HBV S/RT gene were amplified and sequenced to analyze the changes of HBs Ag and RT protein amino acid sequences.Three serotypes(adw,adr,ayw)wild-type recombinant hepatitis B virus surface antigen(r HBs Ag)were used to analyze the subtype specificity of Anti-HBs in Group I patients.Additionally,the HBV vaccinated persons’ sera were used to estimate the neutralize capacity of Anti-HBs against HBs Ag in Group I patients.The statistical analysis was performed using normality test,t test,χ2 test and Fisher exact test.2 The epidemiological characteristics and clinical fetures of patients with simultaneous HBs Ag/Anti-HBs positivity.The results of HBV serological markers in 52070 patients from the First Affiliated Hospital of Fujian Medical University were analyzed.Then,the epidemiological characteristics of HBs Ag and Anti-HBs simultaneously positive patients(the experimental group)and HBs Ag positive and Anti-HBs negative patients(the control group)were compared.The HBs Ag coding region was amplified by semi-nested PCR and sequenced.The statistical differences of the different clinical diagnostic status between the two groups were analyzed,and the relationship between HBs Ag mutation and different clinical diagnoses were explored.【Results】1 The mechanism of co-existence of HBs Ag and Anti-HBs and the effect of patients with simultaneous HBs Ag/Anti-HBs positivity on vaccinations.Results showed that 2.63%(145/5513)chronic HBV infected patients had positive results for Anti-HBs.There was no significant difference in age,sex,HBe Ag positive rate and serum ALT level between Group I and Group II patients(P>0.05).While the ratio of HBV DNA≥ 4 log10 and HBs Ag≥250 IU/m L in Group I patients were lower than those in Group II.The proportion of genotype C HBV in Group I patients(23/35,65.7%)was significantly higher than that of Group II patients(24/58,43.4%).The mutation rate of HBs Ag amino acid in Group I patients was significantly higher than that in Group II patients(1.89% vs.0.95%,P<0.05),especially in the "a" determinant (4.05% vs.1.22%,P<0.05).The common mutation sites in the two groups were s47,s126,s145,s168 and s220(28.57% vs.5.17%,45.71% vs.15.52%,14.29% vs.1.72%,14.29% vs.0.00% and 17.14% vs.3.45%,respectively.P <0.05).HBs Ag and RT protein amino acid mutation in the two groups were statistically significant differences among the segments of s120~s129.Correlation analysis showed that the HBs Ag concentration and HBV DNA load tended to decrease with the increase of HBs Ag mutation rate(0.95%,P<0.05).Furthermore,the mutation rate of HBs Ag increased with the age of the patients(P <0.05).There was nonspecificity between serum HBs Ag and Anti-HBs in most(74.29%,26/35)Group I patients.Interestingly,HBs Ag s G145 R mutations,insertion mutations and continuous amino acid mutations decreased the neutralized capacity of Anti-HBs from HBV vaccinated persons.2 The epidemiological characteristics and clinical fetures of patients with simultaneous HBs Ag/Anti-HBs positivity.The positive rate of HBs Ag was 20.40%(10621/52070),and 2.48%(263/10621)with simultaneous HBs Ag/Anti-HBs positivity.HBs Ag and Anti-HBs co-positive in HBV infected patients was more common in HBs Ag positive patients aged 0~9 years or≥80 years than others,and HBs Ag(+)/Anti-HBs(-)was opposite.The mutation rate of HBs Ag amino acid in Group I patients was significantly higher than that in Group II(1.52% vs 0.81%,P<0.01).The difference was mainly in the major hydrophilic area(MHR)(1.68% vs 0.57%,P<0.01),and the amino acid sequence of HBs Ag in Group I patients contained more unique mutated sites.Between the two groups in the constituent ratio of clinical diagnosis,HBs Ag carriers in Group I was higher than that of Group II(73.00% vs 62.25%,P<0.05),but there was no significant difference between the two groups while patients with chronic hepatitis B(CHB),liver cirrhosis(LC)and hepatocellular carcinoma(HCC)(P> 0.05).The mutation rate of HBs Ag in Group I patients with HBs Ag carriers,CHB and LC was significantly higher than that in Group II patients(1.47% vs 0.65 %,1.28% vs 0.84%,2.21% vs 0.44%,P<0.05),except for patients with HCC(1.97% vs 2.21%,P>0.05).【Conclusion】1 The mechanism of co-existence of HBs Ag and Anti-HBs and the effect of patients with simultaneous HBs Ag/Anti-HBs positivity on vaccinations.Both of HBs Ag mutation and Anti-HBs subtype-nonspecificity contribute to the coexistence of HBs Ag and Anti-HBs in chronic HBV infection.Part of the HBs Ag mutation site in HBs Ag(+)/Anti-HBs(+)patients can lead to changes in the corresponding RT protein,which may affect the function of the RT protein,and these mutations may accumulate.Furthermore,chronic HBV infections with simultaneous HBs Ag/Anti-HBs positivity should be closely monitored to observe the progression of their disease,prevent the occurrence of severe clinical symptoms and mutated HBV spread to the general individual or HBV vaccine recipients.2 The epidemiological characteristics and clinical fetures of patients with simultaneous HBs Ag/Anti-HBs positivity.The incidence of HBs Ag(+)/Anti-HBs(+)was different in different age groups,more common in HBs Ag positive patients aged 0~9 years or ≥80 years than others(10.81% and 7.92%,respectively).The coexistence of serum HBs Ag and Anti-HBs in HBV infection may be related to the change of HBs Ag antigenicity caused by the mutation of HBs Ag(mainly MHR).In addition,the difference in mutation rates of HBs Ag between HBs Ag(+)/Anti-HBs(+)and HBs Ag(+)/Anti-HBs(-)patients was associated with the stage of liver disease. |
PDF Full Text Request