This thesis investigates the epidemiology of hepatitis B virus infection (HBV) and estimates HBV-related liver disease burden in Vietnam and Australia using a cross-sectional study design and mathematical modelling. A population-based seroprevalence survey was undertaken in rural Northern Vietnam. In a sample of 870 study participants, prevalence of anti-HBV core antibody (anti-HBc) and hepatitis B virus surface antigen (HBsAg) was 68.2% and 19.0%, respectively, and hepatitis B e antigen (HBeAg) was detected in 16.4% of the HBsAg-positive group. Factors associated with HBV infection (anti-HBc and/or HBsAg-positive) were age 60 years or older (adjusted odds ratio (AOR), 3.82; 95% CI, 1.35??10.80; P = 0.01), residence in Vu Thu district (AOR, 3.00; 95% CI, 2.16??4.17; P <0.001), hospital admission (AOR, 2.34; 95% CI, 1.33??4.13; P = 0.003) and history of acupuncture (AOR, 2.01; 95% CI, 1.29??3.13; P = 0.002). Household contact with a person with liver disease (AOR, 2.13; 95% CI, 1.29??3.52; P = 0.003), reuse of syringes (AOR, 1.81; 95% CI, 1.25??2.62; P = 0.002) and sharing of razors (AOR, 1.69; 95% CI, 1.03??2.79; P = 0.04) were independent predictors of HBsAg positivity. Alanine aminotransferase (ALT) level was elevated (>40 IU/L) in 43% of the HBsAg-positive group; the proportion of elevated ALT was higher in HBeAg-positive (65%) compared with HBeAg-negative (39%) (P = 0.02). Based on data from the seroprevalence study, other prevalence estimates and HBV natural history parameters, a mathematical model was used to estimate HBV-related liver disease burden in Vietnam. Estimated chronic HBV prevalence increased from 6.4 million cases in 1990 to around 8.4 million cases in 2005 and was projected to decrease to 8.0 million by 2025. Estimated HBV-related liver cirrhosis and hepatocellular carcinoma (HCC) incidence increased linearly from 21 900 and 9400 in 1990 to 58 650 and 25 000 in 2025. Estimated HBV-related mortality increased from 12 600 in 1990 to 40 000 in 2025. To estimate HBV-related HCC incidence among Australians born in the Asia-Pacific region (APR), a mathematical modelling was developed utilising HBV natural history parameters, HBV prevalence estimates in APR countries and immigration data. Chronic HBV cases among the APR-born population increased rapidly from the late 1970s, reaching a peak of 4182 in 1990. Chronic HBV prevalence increased to more than 53 000 in 2005. Estimates of HBV-related HCC increased linearly from one in 1960 to 140 in 2005, with a projected increase to 250 in 2025. Universal HBV vaccination programs in countries of origin had limited impact on projected HBV-related HCC to 2025. HBV-related HCC survival was analysed in a population-based linkage study in New South Wales (NSW), Australia. Between 1994 and 2002, 278 HCC cases notified to the NSW Cancer Registry were linked to chronic HBV infection notifications to the NSW Health Department. The majority of cases were male (83.5%) and overseas born (93.6%); Asian-born cases accounted for 72.1%. Median survival following HCC diagnosis was 15 months. HCC survival was poorer among older age groups (P <0.001), and among cases with regional spread (HR 3.23; 95% CI, 1.83??5.69; P <0.001) and distant metastases (HR 3.85; 95% CI, 2.44??6.08; P <0.001). Sex, region of birth, and study period (1994??1997 versus 1998??2002) were not associated with HCC survival. The results of these studies show that HBV infection remains a major public health challenge in highly endemic countries such as Vietnam. HBV-related liver disease burden in Vietnam was estimated to increase for at least two decades despite the introduction of a universal infant HBV-vaccination program. Similarly, HBV-related HCC among Australians born in the APR was estimated to continue to increase over the next two decades. Survival for HBV-related HCC even in settings such as Australia continues to be extremely poor. Strategies are required to expand HBV treatment to individuals with chronic HBV infection who are at greatest risk of progression to advanced liver disease.

This thesis investigates the epidemiology of hepatitis B virus infection (HBV) and estimates HBV-related liver disease burden in Vietnam and Australia using a cross-sectional study design and mathematical modelling. A population-based seroprevalence survey was undertaken in rural Northern Vietnam. In a sample of 870 study participants, prevalence of anti-HBV core antibody (anti-HBc) and hepatitis B virus surface antigen (HBsAg) was 68.2% and 19.0%, respectively, and hepatitis B e antigen (HBeAg) was detected in 16.4% of the HBsAg-positive group. Factors associated with HBV infection (anti-HBc and/or HBsAg-positive) were age 60 years or older (adjusted odds ratio (AOR), 3.82; 95% CI, 1.35??10.80; P = 0.01), residence in Vu Thu district (AOR, 3.00; 95% CI, 2.16??4.17; P <0.001), hospital admission (AOR, 2.34; 95% CI, 1.33??4.13; P = 0.003) and history of acupuncture (AOR, 2.01; 95% CI, 1.29??3.13; P = 0.002). Household contact with a person with liver disease (AOR, 2.13; 95% CI, 1.29??3.52; P = 0.003), reuse of syringes (AOR, 1.81; 95% CI, 1.25??2.62; P = 0.002) and sharing of razors (AOR, 1.69; 95% CI, 1.03??2.79; P = 0.04) were independent predictors of HBsAg positivity. Alanine aminotransferase (ALT) level was elevated (>40 IU/L) in 43% of the HBsAg-positive group; the proportion of elevated ALT was higher in HBeAg-positive (65%) compared with HBeAg-negative (39%) (P = 0.02). Based on data from the seroprevalence study, other prevalence estimates and HBV natural history parameters, a mathematical model was used to estimate HBV-related liver disease burden in Vietnam. Estimated chronic HBV prevalence increased from 6.4 million cases in 1990 to around 8.4 million cases in 2005 and was projected to decrease to 8.0 million by 2025. Estimated HBV-related liver cirrhosis and hepatocellular carcinoma (HCC) incidence increased linearly from 21 900 and 9400 in 1990 to 58 650 and 25 000 in 2025. Estimated HBV-related mortality increased from 12 600 in 1990 to 40 000 in 2025. To estimate HBV-related HCC incidence among Australians born in the Asia-Pacific region (APR), a mathematical modelling was developed utilising HBV natural history parameters, HBV prevalence estimates in APR countries and immigration data. Chronic HBV cases among the APR-born population increased rapidly from the late 1970s, reaching a peak of 4182 in 1990. Chronic HBV prevalence increased to more than 53 000 in 2005. Estimates of HBV-related HCC increased linearly from one in 1960 to 140 in 2005, with a projected increase to 250 in 2025. Universal HBV vaccination programs in countries of origin had limited impact on projected HBV-related HCC to 2025. HBV-related HCC survival was analysed in a population-based linkage study in New South Wales (NSW), Australia. Between 1994 and 2002, 278 HCC cases notified to the NSW Cancer Registry were linked to chronic HBV infection notifications to the NSW Health Department. The majority of cases were male (83.5%) and overseas born (93.6%); Asian-born cases accounted for 72.1%. Median survival following HCC diagnosis was 15 months. HCC survival was poorer among older age groups (P <0.001), and among cases with regional spread (HR 3.23; 95% CI, 1.83??5.69; P <0.001) and distant metastases (HR 3.85; 95% CI, 2.44??6.08; P <0.001). Sex, region of birth, and study period (1994??1997 versus 1998??2002) were not associated with HCC survival. The results of these studies show that HBV infection remains a major public health challenge in highly endemic countries such as Vietnam. HBV-related liver disease burden in Vietnam was estimated to increase for at least two decades despite the introduction of a universal infant HBV-vaccination program. Similarly, HBV-related HCC among Australians born in the APR was estimated to continue to increase over the next two decades. Survival for HBV-related HCC even in settings such as Australia continues to be extremely poor. Strategies are required to expand HBV treatment to individuals with chronic HBV infection who are at greatest risk of progression to advanced liver disease.