The impact of vaccination and antiviral therapy on hepatitis B and hepatitis D epidemiology

Abstract

The major cause of liver cancer around the globe is hepatitis B virus (HBV), which also contributes to a large number of deaths due to liver failure alone. Hepatitis delta virus (HDV) is as potentially alarming as HBV since life threatening cases are 10 times more likely with HBV-HDV dual infection compared to HBV monoinfection. So far, there is no established effective treatment against HDV and the only preventive action suggested by the World Health Organization is to introduce HBV vaccination for children immediately after birth (newborns) and thus reduce the available pool for HDV infection. Here the main objective is to understand the complex dynamics of HBV-HDV infection in a human population that can inform public health policy makers on the level of different preventive measures required to eliminate HBV and HDV infections. Model simulations suggest that HBV vertical transmission and HBV vaccination rates for newborns are instrumental in determining HBV and HDV prevalence. A decrease in HBV prevalence is observed as vaccination coverage increases and it is possible to eradicate both HBV and HDV using high vaccination coverage of ≥80% in the long term. We further found that HDV presence results in lower HBV prevalence. An application of our model to China revealed that vaccinating every newborn in China will further prevent 1.69 million new infections by 2028 as compared to the current 90% vaccination coverage. Although, higher vaccination coverage of newborns should eliminate both HBV and HDV over a long time period, any short term strategy to eradicate HDV must include additional preventive measures such as HBV adult vaccination. Implementation of HBV adult vaccination programs at a rate of 10% per year over 15 years will further prevent 39 thousand new HDV infections in China by 2028 as compared to HBV vaccination programs solely for newborns.

Figure 1. Schematic representation of HBV/HDV transmission dynamics in a population.

Figure 2. How one virus infectivity impacts the other.

(%) HBV and (%) HDV prevalence in the total population during HBV mono-infection (solid black line) and dual HBV-HDV epidemics (dotted red line and dashed dotted blue line) at years relative to: (A) values of infectivity of acute HDV infection () on the x-axis with also varying as ; (B) levels of suppression by HDV on the transmission of HBV in those dually infected individuals () on the x-axis with also varying as .

Figure 3. How HBV vertical transmission affects HBV and HDV prevalence in a population.

Equilibrium (%) HBV and (%) HDV prevalence in the total population during HBV mono-infection (solid black line) and dual HBV-HDV epidemics (dotted red line and dashed dotted blue line) relative to: (A) vaccination coverage at HBV perinatal transmission probability ; (B) perinatal transmission rate at 10% vaccination coverage ().

Figure 4. Impact of different antiviral therapies on HBV and HDV prevalence.

(%) HBV and (%) HDV prevalence in the total population relative to time in years for: (A)-(B) IFN therapy reducing HBV infectivity alone in HBV mono-infected, HBV-HDV dually infected individuals and vertical transmission probability when introduced at time in the simulation: (C)-(D) prenylation inhibitor therapy reducing HDV infectivity alone when introduced at time (% efficacy of a treatment is equivalent to the % reduction in infectivity).

Figure 5. Application of the model to China.

(%) HBV prevalence in the total population, (%) HBV prevalence in children and (%) HDV prevalence in HBV-infected individuals after the introduction of vaccination programs in 1992 in China. Model simulations (lines) and data (markers) obtained from , –, .

Figure 6. HBV and HDV prevalence under additional preventive measures in China in the next 15 years.

(A) (%) HBV prevalence in the total population, (B) (%) HDV prevalence in the total population, (C) (%) HBV prevalence in children (0–14 years old), and (D) (%) HDV prevalence in HBV infected individuals. Markers were set as for 90% vaccination in children immediately after birth (red dashed line), 100% vaccination in children immediately after birth (blue solid line) and 10% adult vaccination along with 90% vaccination in children immediately after birth (black dashed dotted line).