Parameters

The parameters of the model in this study were probability and cost. The probability parameters were as follows: effective rates of protection (ERP)/PCR of anti-HBs; full vaccination coverage (FCV), the annual rate of HBV infection among the susceptible population; and probability of disease transition after HBV infection. The cost parameters were as follows: the vaccination cost for each strategy for preventing MTCT of HBV; the economic burden of HBD and related diseases; age-specific life expectancy; and discount rate.

When estimating parameters, we first selected results from national surveys or authoritative health institutions [e.g., the Chinese Center for Disease Control and Prevention (CDC)]. If such results were unavailable, meta-analysis results of relevant studies or large-sample randomized controlled trials were used as references. If the methods stated above were unworkable, expert interviews or references to relevant literature from China were used.

We systematically reviewed the clinical literature published in English or Chinese using the database of SinoMed, China National Knowledge Infrastructure, Chongqing VIP Information, and Pubmed from 31 January 2018. To estimate the ERP, we used the following keywords: “hepatitis B vaccin^* OR HBV vaccin^* OR HBIG OR hepatitis B immune globulin, and mother-to-fetus OR mother-to-child OR MTCT OR vertical transmission”. The target population was limited to people from China.

Through literature review, 15 articles were included. We extracted the ERP/PCR of anti-HBs for each strategy from literature or estimated value (Table 2).

ERP/PCR of anti-HBs and FVC for 11 immunization strategies.

ERP, Effective rate of protection; PCR, positive conversion rate; FVC, full vaccine coverage. Since it was not directly available from the literature, the ERP for strategy number 5 was estimated based on the actual situation and other strategies.

We estimated the FVC for each strategy by referencing it to the results from the report of the national planned immunization review in China (2004), the epidemiological survey on national hepatitis B in China (2006), and literature reports from China on preventing MTCT of the HBV in China. These sources provided the relevant information from the provinces of Guangdong, Jiangxi, Shanghai, and Hubei (25, 29–34). We took into account other influencing factors (35) (e.g., difficulty during inoculation and acceptance of different strategies) and determined the FVC based on expert opinion (Table 2).

We obtained data on HBV infection in the Chinese population before hepatitis B vaccination from the National Hepatitis Serum Epidemiology Survey in China (1992). Then, we simulated the infection rate of HBV in China through a revised simple catalytic model using SAS (36). The hyperbolic function was:

where f(a) represents the annual infection rate of a population and a represents age.

Our study was conducted based on the data from HBsAg-positive pregnant women and their newborns. Liaw et al. (37) reported that 10–20% of newborns delivered from HBsAg positive pregnant women who did not have the hepatitis B vaccine postpartum became carriers of chronic HBV infection (37). Edmunds et al. (38) reported that 90% of newborns became carriers of chronic HBV infection after perinatal infection (38). Hence, a newborn delivered from an HBsAg-positive pregnant woman has a 10–20% probability of carrying chronic HBV infection, with an infection rate during the perinatal period (from birth to 1 month of age) ranging between 11.11 and 22.22%. In this study, we assumed that the infection rate of a newborn delivered from an HBsAg-positive pregnant woman from 0 year to 1 year would be the same as that of the general population. According to the formula used for the model, the infection rate of the general population from 0 year to 1 year may be between 22.93 to 38.45%. We estimated that the infection rate of an HBsAg-positive woman could be 34.04–60.67% from 0 year to 1 year; the standard value in the model was 50%. The annual infection rate for other ages was estimated by the formula used to calculate the new infection rate.

The transition probability of each Markov state was obtained from the publicly available research. If multiple studies had the same probability of disease transition, then we took the mean value. The maximum value and minimum value of each transition probability reported in the literature were taken as the value range of sensitivity analysis.

The probability of disease transition after HBV infection in the Markov model was based on the relevant literature in China (Table 3).

Status and probability of disease transition after HBV infection.

This study was based on a public healthcare system perspective. The cost of preventing MTCT of HBV comprised direct costs and indirect costs. Direct costs included the expense of HBIG or HBV vaccination, transportation and storage (including cold chain) expenditure, service and material expenditure during inoculation, and transportation costs for immunization of pregnant women. It was calculated based on the costs of medical services at Chinese non-profit medical institutions indicated in the research literature. Indirect costs included the compensation for absence from work for the pregnant women and their chaperones.

In China, the whole process of immunization against HBV involves three stages: (a) the provincial CDC is responsible for the procurement, storage, and transportation of the hepatitis B vaccine within the province; (b) the municipal, district, and national CDCs are responsible for the distribution, transportation, and storage of the vaccine within each jurisdiction; and (c) immunization clinics at all levels are responsible for vaccination. According to research articles assessing inoculation expenditures (vaccine procurement, cold-chain management, administrative expenses, and labor payment) of five hospitals, 92 CDCs, 177 community healthcare centers, and 476 village clinics in Shanghai, Shandong, Hunan, and Gansu Provinces, the cost of one injection was US$ 0.35–0.50 (14, 68). The price of the hepatitis B vaccine and HBIG were determined according to the purchase price paid by provincial CDCs.

Transport expenses for pregnant women injected with HBIG (which included bus, taxi, and personal cars) and indirect costs (which included compensation for absence from work for pregnant women and their companions) were extracted from literature (61) (Table 4).

Cost for 11 immunization strategies (in USD).

The economic burden of HBD and related diseases included the direct economic burden and indirect economic burden, which were based on a systematic review of the literature. The “direct economic burden” referred to consumed social and economic resources with regard to the treatment of HBD and related diseases, which included direct medical costs and nonmedical costs. The “indirect economic burden” referred to the indirect economic losses caused by HBD and related diseases to the society.

We identified 12 studies focusing on HBD burden and extracted the information listed in Table 5 (63, 69–78). The studies involved 7,409 respondents from Zhejiang, Guangdong, Shanghai, Shanxi, Gansu, Jiangsu, and Shandong Provinces and reported the burden of HBD and related diseases.

Burden of hepatitis B disease and related diseases (in USD).

Age-specific life expectancy was a parameter required for the simulation of the Markov model after the HBV-susceptible population had become infected and it determined the number of cycles of the Markov model. It was determined using the Global Health Observatory data available on the World Health Organization's (WHO) website (79). Based on the Chinese Statistical Yearbook (2016), we determined the life expectancy of the Chinese population to be 76 years (80). The number of cycles in the Markov model was set at 76. Mortality caused by severe HBD ensued from acute infection, decompensated cirrhosis, and liver cancer. We determined the mortality associated with other health statuses in the Markov model based on age-specific mortality in the general population under natural conditions. The natural mortality rate of the whole population from 0 to 74 years adopted the age-specific mortality rate of Chinese residents of small- and medium-sized cities according to the Health Statistics Yearbook of China (2011) (81). Linear interpolation was used to obtain the mortality per year.

The effect of immunization had long-term benefits, and the outcome of the disease after HBV infection was also a long-term process. To eliminate the time effect on the currency, the costs and benefits in our study were discounted. The discount rate of 5% was calculated based on similar studies conducted in China. The range of values of the discount rate used in the sensitivity analysis was 3–6%, as recommended by the World Bank and similar studies conducted in the US, Sweden, and the United Kingdom.