Epidemiological study of hepatitis B and hepatitis C infections in Northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study

Using the expected HBsAg prevalence for different age groups in the study (0.3% for age 1–4 years, 3% for age 5–14 years, 4% for age 15–29 years, 9% for age 30–59 years), a level of confidence of 95%, power of 80%, and tolerance error ranging from 20 to 75% (75% for age 1–4 years, 25% for age 5–14 years, 25% for age 15–29 years, 20% for age 30–59 years), estimating a response rate of 80%, the desired sample size was 6518, and an additional 1613 Children < 5 years, 1412 children 5–14 years, 1863 participants 15–29 years and 1227, adults 30–59 years. A total of 6541 individuals in Changchun City of Northeastern China were enrolled in this cross-sectional study from June 2016 to August 2016. The target study sample was randomly chosen from residents who were aged < 60 years and had lived in the city for at least 6 months using multistage stratified cluster random sampling. Briefly, in the first stage, probability proportional to size (PPS) sampling was used to randomly choose clusters of 15 districts/counties from each region. In the second stage, one study individual was randomly chosen from each household in the participating communities.

Prior to enrollment, written informed consent was obtained from each participant or their guardian, if the patient was a minor aged < 16 years. The present study was reviewed and approved by the Ethics Committee of the Changchun Center for Disease Control and Prevention.

A questionnaire was designed to collect information on the demographic characteristics, history of receiving the hepatitis B vaccine, surgical procedures, blood transfusion, traumatic or cosmetic operations, acupuncture, teeth cleaning, and HBV and HCV infection in family members. All investigation forms were completed by physicians through face-to-face interviews. For children aged < 16 years, the information was provided by a parent or legal guardian.

For serological examinations, blood samples were collected without anticoagulant from each participant (5 mL from the individuals aged > 2 years and 2 mL from those aged < 2 years). The samples were subsequently separated by centrifugation at 1800×g for 10 min at room temperature (RT) and stored at − 80 °C. The procedures for sample collection and storage were performed as soon as possible and no longer than 6 h according to the standard protocol. Serological examinations were performed in the central laboratory. Serological markers for HBV and HCV, including HBsAg, hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B core antibody (HBcAb), and HCV antibody (HCVAb) were determined by enzyme-linked immunosorbent assays (ELISAs) (Kehua Bio-Engineering Co. Ltd., Shanghai, China) in accordance with the manufacturer’s instructions. Briefly, two negative controls, two positive controls, and one blank control were included in each plate. For HBV- or HCV-positive participants, repeated ELISAs were conducted (Abbott Microparticle Enzyme Immunoassay Method; Abbott Diagnostics Divisions, Santa Clara, CA, USA).

The information obtained from the questionnaire form was entered into a database. The data were separated according to age and sex due to the complex sampling design of the study as well as according to response and analyzed using SPSS (SPSS, Inc., Chicago, IL, USA). Prevalence rates and constituent ratios as well as their 95% confidence intervals (CIs) for multi-morbidity were calculated.

A total of 6642 participants were recruited for this study, and 101 were excluded from the final analysis due to the lack of complete questionnaire information or medical examination. The other 6541 participants responded to the questionnaire, for a response rate of 98.5%. Tests for sero-markers for HBV and HCV infections revealed that 127 cases were positive for HBsAg (1.9%), 3863 positive for HBsAb (59.1%), 4158 positive for HBcAb (63.6%), 28 positive for HBeAg (0.4%), 721 positive for HBeAb (11.0%), and 20 (0.3%) positive for HCVAb. After age-adjustment to represent the Changchun population, the weighted prevalence rates were: HBsAg (3.8%); HBsAb (55.2%); HBcAb (60.9%); HBeAg (0.72%); HBeAb (14.9%); and HCVAb (0.36%). Age was found as a major factor for the differences between unweighted and weighted prevalence rates. As shown in Table 1, the prevalence rates of HBsAg varied markedly among the study participants in the different age groups. The highest HBsAg-positivity rate found among the study subjects aged 40–49 years, whereas those individuals aged 50–59 years showed the highest prevalence rate of anti-HCV-positive results. The prevalence trend for HBcAb was similar to that for HBsAg, with the highest rate occurring among participants aged 50–59 years. The prevalence trend for HBsAb was different from that for HBsAg, showing a decrease according to advancing age from 84.8% (age < 1 year) to 49.0% (age 50–59 years). Furthermore, gender differences in the HBsAg- and anti-HCV positivity rates were observed, with higher rates found among males compared with females.

With the Chinese government implementing the policy of planned hepatitis B vaccine immunization nationwide and strengthening the blood management system in 2002, we anticipated that receiving the hepatitis B vaccine would have a beneficial impact on the HBsAg-positivity rates in the study participants. As expected, children who were born after the successful implementation of the public policy exhibited the highest coverage rate by the hepatitis B vaccine (94.2%) (Fig. 1a). Notably, children aged 0–14 years had a significantly lower HBsAg-positivity rate (0.2%) than individuals in any of the remaining age groups (Fig. 1b).

Next, we compared the HBsAg-positivity rates obtained in this study with those reported in the epidemiological serosurvey of hepatitis B conducted in 2006 [4]. Similar prevalence rates of HBsAg were found among children aged 1–4 years in both studies. However, for the other age groups (aged > 5 years), the HBsAg-positivity rates in our serosurvey were lower than those in the 2006 national survey (Fig. 2a). In comparison with the previous epidemiological serosurvey of hepatitis B in 2006 [4], we observed in the present study that the HBsAb-positivity rates were slightly higher in study participants aged > 15 years, but lower in children aged 0–14 years (Fig. 2b).

Our study also developed a questionnaire about basic HBV knowledge and conducted a survey among these participants. Overall, 67.2% of the participants realized that vaccination with the hepatitis B vaccine can prevent HBV infection and 38.9% of participants know that safe blood donation and blood transfusion are valid for impeding HBV transmission. However only 32.9% of the participants knew that teeth extraction and endoscopy should be carried out in a formal hospital. At the same time, 27.6% of participants did not know how to prevent hepatitis B. Our results also showed that only 16.5% of the HBsAg-positive population previously knew that they were positive for HBsAg (Table 2).