Investigation Of The Value Of Serum Hbsag Levels In The Prediction Of Relapse After Withdrawing Nucleoside Anologues To The Cessation Criteria

Obsjective: Serum HBsAg was thought to be an important marker to HBV infection, results preliminary showed that it was corelated to cccDNA to a certain extent in recent years, and some researchers believe that serum HBsAg quantity could be used to be an indicator to estimate the effect of antiviral therapy by interferon, but it was rare in nucleoside anologues. We aimed to study the relationship between the quantity of serum HBsAg and HBsAg, cccDNA, tDNA in the heaptocytocytes and to study the value of serum HBsAg levels in the prediction of relapse after withdrawing nucleoside anologues to the cessation criteria in chronic hepatitis B patients.Methods: 77 chronic hepatitis B patients received nucleoside anologues treatment were studied, 33 patients treated with lamivudine (LAM), 23 patients treated with adefovir dipivoxil (ADV), 13 patients treated with entecavir(ETV), 4 patients treated with telbivudine (LDT), 4 patients treated with LAM plus ADV. 38 patients were positive for HBeAg, 39 patients were negative for HBeAg. Patients were followed up to relapse, the non- relapse patients were followed up to more than 6 months after stopping treatment, the last following up time was the end-point of study, the patients who relapse within 6 months post-treatment were counted into relapse group 1, and the patients who relapse within 12 months were counted into relapse group 2, the patients who achieved sustained virologic response (SVR) more than 6 months were counted into SVR group 1, and who achieved SVR more than 12 months were counted into SVR group 2. Quantitative serum HBsAg levels were assessed by chemiluminescent immunoassay(ABBOTT), the relapse groups were assessed at the end of treatment and at the time of relapse, the SVR groups were assessed at the end of treatment and at the time of 6 months, 12 months post-treatment. 56 patients had completed posttreatment liver biopsy specimens, the quantitative of cccDNA, tDNA in the heaptocytocytes were assessed by FQ-PCR, the quantitative of HBsAg in the heaptocytocytes were assessed by chemiluminescent immunoassay(ABBOTT). The relationships between the quantity of serum HBsAg and HBsAg, cccDNA, tDNA in the heaptocytocytes were analysised, and the relationships between the quantity of hepatic tissue HBsAg and cccDNA, tDNA were analysised, the end of treatment serum HBsAg levels were compared for the relapse group and the SVR group, the ROC curves were analysised for HBsAg quantity to predict relapse at the end of treatment until 6 months and 12 months post-treatment, the HBsAg levels at the end of treatment were divided into 3 subgroups, the cumulative relapse rates were compared in these 3 subgroups, the increase amplitude of HBsAg levels post-treatment were compared in the relapse group and the SVR group. Results: (1) There was a positive correlation between the quantity of hepatic tissue HBsAg and serum HBsAg(r=0.538,p=0.000), there was a low positive correlation between the quantity of HBV cccDNA and the hepatocytes and serum HBsAg(r=0.262, p=0.049), and there was a high positive correlation between the quantity of hepatic tissue tDNA and serum HBsAg(r=0.691, p=0.000), there was no correlation between the quantity of hepatic tissue HBsAg and cccDNA(r=0.176, p=0.213), there was a positive correlation between the quantity of hepatic tissue HBsAg and tDNA(r=0.0.405,p=0.003);(2)The level of the serum HBsAg at the end of treatment in the relapse group 1 was higher than the SVR group 1(3.371og10 IU/ml VS 3.041og10 IU/ml, p=0.035); (2)The level of the serum HBsAg at the end of treatment in the relapse group 2 was higher than the SVR group 2 (3.361og10 IU/ml VS 2.73 1og10 IU/ml, p=0.009). (3) The level of serum HBsAg at the end of treatment >3.25 log 10IU/ml as the cutoff value has a sensitivity of 0.667, specificity of 0.630, positive predictive value of 0.667, and negative predictive value of 0.75 for relapse within 6 months, the area under ROC was 0.643, P= 0.035; the level of serum HBsAg at the end of treatment >3.21 log 10IU/ml as the cutoff value has a sensitivity of 0.641, specficity of 0.679, positive predictive value of 0.735, and negative predictive value of 0.613 for relapse within 12 months, the area under ROC was 0.689, P= 0.009.(4) the HBsAg levels at the end of treatment were divided into 3 subgroups: HBsAg<2log10IU/ml,HBsAg=2-3log10IU/ml,HBsAg>3log10IU/ml, the cumulative relapse rate within 6 months in these 3 groups were 0%,36.4%,48.9% respectively, P=0.025; and 0%,50%,71.8% respectively within 12 months ,p=0.004; (5) The increase amplitude of HBsAg level at the time of relapse and at the end of treatment in the relapse group 1 was higher than the increase amplitude of serum tilters at the end of treatment until 6 months post-treatment and at the end of treatment in the SVR group 1(1.471og10 IU/ml VS -1.87 1og10 IU/ml, P=0.047); The increase amplitude of serum tilters at the time of relapse and at the end of treatment in the relapse group 2 was higher than the increase amplitude of serum tilters at the end of treatment until 12 months post-treatment and at the end of treatment in the SVR group 2(0.811og10 IU/ml VS -1.98 1og10 IU/ml, P>0.05).Conclusion: (1) The serum HBsAg can reflect the levels of HBsAg,cccDNA,tDNA in the heaptocytocytes in some degree.(2) The level of serum HBsAg at the end of treatment could be a reference indicator to decide the end-point of treatment for antiviral therapy by nucleoside anologues.(3) It is beneficial to predictor relapse to monitoring the serum HBsAg post treatment.