Long-term Efficacy Of Hepatitis B Vaccine And HBeAg Seroconversion During Chronic Infection

Objective1To assess the long-term efficacy of hepatitis B vaccine integrating infection rate, carrier rate, anti-HBs positive rate and immune memory.2To study HBeAg spontaneous seroconversion rate among chronic HBV infection.3To analysis HBeAg sero-conversion rate among chronic hepatitis B patients with/without antiviral therapy.Methods1Assessment on long-term efficacy of hepatitis B vaccine(1) The1986birth cohort with HBV vaccination in Nanshi District (now Huangpu District) was followed regularly. Serum samples were collected at each follow-up to test HBsAg, anti-HBc, and anti-HBs. The positive rate of anti-HBs, as well as infection rate were calculated.(2) Blood samples and the follow-up data from12peoples who was born in1986-1989, and induced anti-HBs antibody after receiving full course vaccination at the birth, were collected from Zhengding, Hebei province. After testing the anti-HBs antibody level using Architect i2000system (Abbott, Abbott Park, IL, USA), the proportion of detectable memory T cell, as well as its function tested by means of flow cytometry and fluorospot, were compared between anti-HBs positives and negatives.2Longitudinal cohort study on the spontaneous HBeAg seroconversion among chronic HBV carrierA chronic HBV infection cohort with172HBsAg/HBeAg positive carriers was set up through the cross-sectional serological survey in8villages of Zhengding county, Hebei province in1999,2005and2006. Serum specimens were collected from all carriers during the follow-up at2010and2012, and were tested for anti-HBs, HBsAg, anti-HBe, HBeAg, HBV DNA, as well as ALT.3Meta analysis of HBeAg seroconversion among Chronic hepatitis B patientsLiteratures published before September2012, both in English and Chinese were searched in PubMed, SinoMed, and CNKI, and reviewed by applying standardized algorithms. HBeAg seroconversion rate under different circumstance were grouped, and the pooled average rates, as well as its95%confidence intervals were estimated using random effect model.Results1Assessment on long-term efficacy of hepatitis B vaccine(1) The1986birth cohort was followed for23years. In total,5,993blood samples were collected over13serologic follow-ups. The anti-HBs positive rate declined from89.0%at the first year to18.8%at the23rd year after vaccination. However, HBV infections (anti-HBc) and HBV carrier rate (HBsAg) did not change throughout the23-year follow-up.(2) Compared to the testing with flow cytometry, the functional HBsAg-specific memory T cells could be well detected by fluorospot, and the proportions of responded memory T cell did not associate with anti-HBs level.2Longitudinal cohort study on the Spontaneous HBeAg seroconversion among chronic HBV carriersLoss of HBeAg was detected from32carriers, the annual rate was2%(95%CI:1.4-2.8%). Of these, HBeAg seroconversion occurred in26carriers, the annual spontaneous HBeAg seroconversion rate was1.6%(95%CI:1.1-2.4%).3Meta analysis of HBeAg seroconversion among chronic hepatitis B patients After literature searching and reviewing,501articles were included in the final analysis. Of these,305articles were published in Chinese, compared to196in English. Meta-analysis showed that, without antiviral treatment, annual spontaneous HBeAg seroconversion rate among chronic hepatitis B patients was7.9%(95%CI:6.3-9.5%). After one year treatment with adefovir, entecavir, lamivudine, Telbivudine, interferon, or PEG-interferon, the HBeAg seroconversion rate was14.3%(95%CI:13.0-14.1%),19.6%(95%CI:12.3-26.8%),20.8%(95%CI:18.5-23.1%),26.5%(95%CI:22.8-30.1%),29.3%(95%CI:25.3-33.3%), and36.0%(95%CI:30.0-42.0%) respectively..Conclusion1In terms of the infection rate, carrier rate, and the detectable memory T cell, the promising protection offered by the plasma-derived HBV vaccine at the23rd year after vaccination was demonstared. There is no eveidence to indicate the need for booster dose.2Spontaneous HBeAg seroconversion could be observed among chornic HBV carriers and chronic Hepatitis B patients. However, it was much lower in carrier, compared to that in patient. Out of the six antiviral therapies which were regular used in practice, interferon, especially peg-interferon displayed the best performance on the HBeAg seroconversion, followed by Telbivudine, and entecavir. Normally, HBeAg seroconversion coming along with the significant decrease of HBV DNA and ALT level.