Liping Shen

Change in Hepatitis B Virus Large Surface Antigen Variant Prevalence 13 Years after Implementation of a Universal Vaccination Program in China

ABSTRACT A nationwide hepatitis B virus (HBV) vaccination program was implemented in China starting in 1992. To study the change in HBV variant prevalence with massive immunization, large HBV surface protein (LHBs) genes from HBV surface antigen (HBsAg)-positive sera were amplified and sequenced. The prevalences of LHBs mutants were compared between the 1992 and 2005 surveys in child and adult groups. The prevalence of “α” determinant mutants in the children increased from 6.5% in 1992 to 14.8% in 2005, where the G145R mutant occurred most frequently. In contrast, mutation frequencies showed little difference between 1992 (9.4%) and 2005 (9.9%) in adults. Moreover, compared to the 1992 survey, the child group surface (S) protein mutation frequency specifically increased (P = 0.005) in the 2005 survey, but the pre-S region mutation frequency did not show a significant difference (P > 0.05). However, the mutation frequency in the adult group increased in both the pre-S and S regions. Furthermore, the frequencies of the disease-related pre-S2 deletion and start codon mutations were significantly higher in the adult groups than in the child groups in both the 1992 and 2005 surveys (P < 0.01). Massive immunization enhances the HBV S protein mutation; the prevalence of LHBs mutants, particularly disease-related mutants, tends to increase with patient age.

Risk factors associated with immunoprophylaxis failure against mother to child transmission of hepatitis B virus and hepatitis B vaccination status in Yunnan province, China

OBJECTIVE To explore the risk factors associated with immunoprophylaxis failure against mother to child transmission of hepatitis B virus (HBV) and hepatitis B vaccination status in Yunnan province, China. METHODS Multicenter cluster sampling was used to select pregnant women who were positive for hepatitis B surface antigen (HBsAg). HBV immunoprophylaxis was carried out for the newborns. Blood samples were collected and tested for HBV markers from 7 to 10 month old infants. The factors were analyzed by univariate and logistic regression. RESULTS A total of 2765 mothers and their infants were enrolled. The failure rate of prevention of mother to child transmission (PMTCT) was 4.12%. The rate of timely HepB1 vaccination within 24h was 98.04%, the rate of three-dose vaccination was 92.30% and the rate of hepatitis B immune globulin (HBIG) administration was 68.97%. Place of residence, maternal education, gestational age and birth weight were related to administration of HBV immunoprophylaxis. It was remarkable that the rate of HBIG administration of infants was only 63.89% with whose mothers were both HBsAg and hepatitis B e antigen (HBeAg)-positive. Further analysis showed that there were three risk factors associated with HBV immunoprophylaxis failure: mothers who were positive for HBsAg and HBeAg, maternal HBVDNA level, and HBIG administration or not. CONCLUSIONS PMTCT of HBV was well implemented in Yunnan. However, in order to achieve optimal prevention of vertical HBV transmission, it is mandatory to make additional efforts to improve the implementation of regulatory HBV immunoprophylaxis, especially for HBsAg-positive pregnant women.

Efficacy of yeast-derived recombinant hepatitis B vaccine after being used for 12 years in highly endemic areas in China.

OBJECTIVE To evaluate the long-term efficacy and duration of yeast-derived recombinant hepatitis B vaccine in hepatitis B virus (HBV)-endemic areas. METHOD A cross-sectional investigation was carried out in five HBV-endemic areas. Children who were born between 1997 and 2008 and vaccinated with yeast-derived recombinant hepatitis B vaccine were selected. Serum samples were taken to test HBV infection markers by microparticle enzyme immunoassay, and the results were compared to those before vaccination. RESULTS 7066 subjects were enrolled. The average adjusted hepatitis B surface antigen (HBsAg) prevalence was 1.02%. HBV core antibody (anti-HBc) prevalence was 3.54%. The overall percentage of HBsAg(-)&Anti-HBc(-)&Anti-HBs(+) was 61.34%. With time after immunization, the percentage annually decreases from 86.11% in 2008 to 49.80% in 1997. Geometric mean concentration (GMC) of anti-HBs decreased significantly annually. The portion of GMC=100-999.9 mIU/ml was 48.0% in 2008, and decreased to 16.7% in 1997. CONCLUSION HBsAg prevalence decreased dramatically. This shows that the yeast-derived recombinant hepatitis B vaccine is effective and stable after being used for 12 years in HBV-endemic areas. It is not suggested to carry out booster immunization.

Molecular epidemiological study of hepatitis B virus genotypes in Southwest, China

Hepatitis B virus (HBV) is highly endemic in Southwest China; an area with many ethnic minorities. Information about the genetic distribution of HBV is still limited. In 2010, a multistage cluster sampling method was carried out in the Southwest China. Five hundred forty serum samples of participants were collected. Polymerase chain reaction followed by nucleotide sequencing of parts of the HBV S and C genes was performed. HBV genotype and subgenotype were determined. Recombination analysis was carried out. HBV infectious markers, HBV DNA and mutations in the basic core promoter (BCP) A1762T/G1764A and G1896A were analyzed. The results show us that HBV genotypes C/D recombinant (38.6%), B (31.6%), and C (23.3%), were predominant in Southwest China. C/D4 (96.8%) was endemic in the Tibetan and B2 (43.5%) in Han, and C1 (66.7%) was predominant in the Yi minority. 67.5% (56/83) of genotype C/D was Hepatitis B surface antigen (HBsAg) positive/Hepatitis B e antigen (HBeAg) positive/HBV DNA≥20,000 IU/ml, BCP A1762T/G1764A double mutation was frequent in genotype C and C/D, and G1896A was frequent in B and B/C. Thus, HBV genotypes distribution differed significantly in area and minority in Southwest China. C/D recombinant is endemic in the Tibetan, while B, C genotypes are predominant in Han minority. C/D recombinant exhibits higher frequency with HBeAg positive, high level of HBV DNA and BCP A1762T/G1764A double mutation. J. Med. Virol. 86:1307–1313, 2014.

The long-term efficacy, 13-23 years, of a plasma-derived hepatitis B vaccine in highly endemic areas in China.

OBJECTIVE To evaluate the long-term effectiveness of the plasma-derived hepatitis B vaccine that has been applied widely in five areas of China where HBV prevalence was highly endemic. METHOD A cross-sectional investigation was conducted in 2009 at five HBV surveillance sites around China. The target study subjects of 6772 were born between 1986 and 1996 and received plasma-derived HBV vaccine. Serum samples were collected to test for HBV markers using the microparticle enzyme immunoassay. RESULTS The number of participants enrolled was 6772. The average hepatitis B surface antigen (HBsAg) prevalence was 2.01%. The birth dose group included 5052 children. In this group, the average positive rates of HBsAg and hepatitis B core antibody (anti-HBc) were 1.58% and 6.39%, respectively, and these values declined gradually from 1986 to 1996. The positive rates of anti-hepatitis B surface antibody (HBs) and the geometric mean concentration (GMC) of anti-HBs-positive subjects were 41.69% and 115.8mIU/ml. CONCLUSION The long-term effectiveness of the plasma-derived hepatitis B vaccine still provided protection 13-23 years after vaccination. It seems that a booster dose is not necessary. Enhancing the rate of the birth dose within 24h is one of the most important measures to prevent and control HBV infection.

Development of a hepatitis delta virus antibody assay for study of the prevalence of HDV among individuals infected with hepatitis B virus in China

Co‐infection with hepatitis delta virus (HDV) and hepatitis B virus (HBV) has been shown to be associated with a more severe form of acute and chronic hepatitis. Cloning and expression of recombinant HDV antigen (rHDAg) in Escherichiacoli are described. Using purified rHDAg, a cost‐effective indirect anti‐HDV enzyme‐linked immunosorbent assay (ELISA) kit was developed. Direct comparison of 15 known HDV‐positive sera and 15 HDV‐negative sera showed concordance agreement between the new assay kit and the Abbott Murex Anti‐Delta (total) kit. In addition, 1,486 hepatitis B surface antigen (HBsAg) positive blood samples collected from various areas of China were tested using this indirect anti‐HDV ELISA. It was found that 1.2% (95% CI: 0.7–1.9%) of the samples were anti‐HDAg positive. It is suggested that the prevalence of HDV and HBV co‐infection in China is relatively low. J. Med. Virol. 84:445–449, 2012.

Prevalence and risk factors of hepatitis C among former blood donors in rural China

BACKGROUND Illegal commercial plasma and blood donation activities in the late 1980s and early 1990s caused a large number of hepatitis C virus (HCV) infections in rural areas of China. METHODS A cross-sectional survey was carried out in 2008, in which all residents in a former blood donation village in rural Hebei Province were invited for a questionnaire interview and testing for HCV antibodies. Questionnaires were administered to collect information about their personal status and commercial blood donation history, and HCV antibodies were tested by enzyme immunoassay. RESULTS Of 520 villagers who participated in the interviews, 236 (45.4%) reported a history of selling whole blood or plasma. HCV seropositivity was confirmed in 148/520 (28.5%) interviewees and 101/236 (42.8%) former commercial plasma and blood donors. Selling plasma was the strongest independent predictor of HCV seropositivity (p=0.0037). Past history of an operation was also independently associated with HCV infection (p=0.0270). CONCLUSIONS Unsafe practices during illegal plasma donation led to a high risk of HCV seropositivity for donors during the late 1980s and early 1990s. Many infected people suffered chronic hepatitis from that time onwards and urgently needed treatment and care.

Epidemiology of Hepatitis C Virus Infection and Risk Factor Analysis in the Hebei Province, China

Background In 1985, a hepatitis C virus (HCV) outbreak caused by plasmapheresis donation was reported in the Hebei Province, China. However, studies assessing the epidemic features and risk factors of HCV in the general population of Hebei have been limited until now. Methods The multicenter cluster sampling method was used to collect samples. The participants were interviewed. Relevant information was obtained from the general population using a standardized questionnaire, and association and logistic regression analyses were conducted. Serum samples were taken to test anti-HCV by enzyme immunoassays. Results A total of 4562 participants from 11 cities of the Hebei Province were enrolled. The average anti-HCV positive rate was 0.62% (29/4562), which was 1.07% in the rural population, compared with 0.22% in the urban population. The anti-HCV positive rate in the 40–59-year age group was higher than in those aged <40 years. History of blood transfusion and transmission in families were the main risk factors for HCV infection in this area. Conclusion The anti-HCV positive rate in Hebei has decreased significantly from that two decades ago. Safety of blood products and health education about HCV still need to be improved.

Long-term efficacy of 10–12 years after being immunized with Chinese hamster ovary cell derived hepatitis B vaccine in Chinese Rural Communities ☆

OBJECTIVE To evaluate the long-term efficacy of Chinese hamster ovary (CHO) cell derived hepatitis B vaccine in country community in China. METHODS A cross-sectional investigation was carried out. Children who were born between 1997 and 1999 and vaccinated with the three doses of CHO-derived hepatitis B vaccine were selected as study objects. Their serum samples were taken to test for hepatitis B virus (HBV) markers, and the results were compared to that before vaccination. In addition, for HBsAg positive children, their mothers were visited. RESULTS 1254 Children were enrolled in the study. The prevalence of HBsAg was 0.24% and the vaccine efficacy was 97.0%, similar to that of yeast derived hepatitis vaccines. Among 3 mothers of HBsAg positive children, 2 were HBsAg positive, indicating maternal HBV transmissions. CONCLUSION The long-term efficacy of the CHO-derived hepatitis B vaccine is good and after vaccination maternal transmission is the most important route of spreading HBV.

Risk factors related to the failure of prevention of hepatitis B virus Mother-to-Child transmission in Yunnan, China

OBJECTIVE To investigate the relationship between the failure of prevention of hepatitis B virus Mother-to-Child transmission and HBV serological pattern, viral load as well as HBV genotypes. METHODS 2765 pairs of mother-infant matched samples were collected. These pregnant women were HBsAg positive and delivered at hospital from January 1st, 2011 to June 30th, 2011. Of these samples, 26 pairs of sera samples were randomly selected from 114 pairs of samples which failed in the prevention of hepatitis B virus Mother-to-Child transmission. Serological tests, viral load and genotype detection were performed for further analysis. Additionally, the selected subjects were followed and tested again in 2014. RESULTS HBeAg positive rates were 76.92% and 69.23% in mother group and infant group respectively, showed no statistical difference. The average HBV DNA levels were >2×105IU/ml in both mother group and infant group. Genotype analysis revealed that 11 pairs of mother-infant matched samples belonged to C gene type and another 11 pairs were B gene type. Different genotypes were observed in 4 pairs of mother-infant matched samples. CONCLUSION HbeAg positive and high HBV DNA level were two major risk factors of HBV mother to child transmission. Additionally, nosocomial infection was another potential way of HBV vertical transmission, especially in remote area of Yunnan province.