Mathematical Modeling of Hepatitis D virus

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Copyright: Goyal, Ashish
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Abstract
The major cause of liver cancer around the globe is hepatitis B virus (HBV). With 400 million chronic carriers, it causes almost one million deaths every year. Almost 5 to 10% of these chronic HBV carriers are also infected with hepatitis D virus (HDV). HDV is one of the only two known human viruses that require a helper virus (HBV). In conjunction with HBV it increases adult morbidity and mortality by 5 to 10 times. There is no established effective treatment or vaccination against HDV making it a significant worldwide health issue. This project aims to better quantify the epidemiology and in vivo dynamics of HBV and HDV. The project initially investigates the in vivo dynamics of these infections. Since HBV is necessary for HDV replication, we first determine and differentiate those factors which result in successful clearance of acute HBV infection or are reasons behind its persistence in the presence of a competent immune system. We find that additional mechanisms such as the complete loss of the HBV viral genome during cellular proliferation may play an important role in immune-mediated clearance. Cell-to-cell transmission can be a reason behind persistence of acute HBV infection. In addition, very little is known about interactions between these two viruses except for the inhibition of helper virus pre-genomic RNA production and use of hepatitis B surface antigens by HDV. We find that HDV also may inhibit the transportation of HBV relaxed circular DNA from the cytoplasm to the nucleus causing lower covalently closed circular DNA accumulation. Given the sparsity of experimental data, these problems were investigated using spatial and agent-based 2-D and 3-D deterministic and stochastic models of HBV and HDV viral dynamics. The in vivo analyses provided a basis to better understand infectivity of individuals and the impact on epidemiology of these infections. We constructed models describing the epidemiology of HBV and HDV, and used optimization routines determining the best resource allocation strategy among preventive and antiviral options. The results indicate that treatment for dually infected individuals should be included under the current healthcare budget in China. Additionally the cost-effectiveness of nucleoside analogues, Interferon (IFN) and Peg-IFN was also evaluated. We estimated that Peg-IFN generates the most quality-adjusted-life-years and is cost-effective for all age groups at current willingness-to-pay in China.
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Author(s)
Goyal, Ashish
Supervisor(s)
Murray, John M
Cai, Anna
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Publication Year
2016
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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