Risk factors, correlates and disease burden of chronic hepatitis B virus infection in Chinese adults

Thesis

Background: China has the largest burden of chronic hepatitis B virus infection (HBV) in the world, where it remains a leading cause of morbidity and mortality, however there are inconsistencies in the evidence about chronic HBV prevalence, correlates of infection and associated disease burden in Chinese adults.

Methods: Firstly, a systematic review and meta-analysis was performed to summarize correlates of chronic HBV infection in Chinese adults. Next, data-analysis was performed using the China Kadoorie Biobank (CKB), a prospective cohort study of > 0.5 million adults enrolled between 2004–2008 from ten geographically diverse areas of China, where hepatitis B surface antigen (HBsAg) was measured at baseline. Cross-sectional correlates of HBsAg positivity were explored for non-genetic and genetic factors via logistic regression models, while associations with risk of incident diseases, including liver disease, extra-hepatic cancers and cardiovascular diseases, were explored via Cox regression, in addition to calculation of absolute risks of disease.

Results: In the systematic review and meta-analysis, 22 correlates of chronic HBV infection were identified, including a range of sociodemographic, behavioural and medical factors. In CKB chronic HBV prevalence was 3.0%, and of HBsAg positive participants only 10.8% had a baseline diagnosis, of whom 19.4% were on treatment. There were significant cross-sectional associations between younger age, male sex, lower level of education, history blood transfusion and poor self-rated health, generally consistent with findings from the systematic review. For genetic variants associated with HBsAg positivity, 17 of 18 single nucleotide polymorphisms (SNPs) previously associated with chronic HBV in genome wide association studies (GWAS) were replicated. Over 11 years of follow-up, chronic HBV was significantly associated with a range of liver and non-liver diseases, where in addition to liver disease (HR 9.56, 95% CI 9.11–10.00) and hepatocellular carcinoma (24.67 [20.30–29.98]), infection was also significantly associated with extra-hepatic cancers (non-Hodgkin’s lymphoma, cholangiocarcinoma, gastric, colorectal cancer and ill-defined cancers) and higher risk of intracerebral haemorrhage (ICH, HR 1.29 [1.16–1.44]).

Conclusion. Chronic HBV is a pressing global health challenge, which has a high disease burden in China requiring urgent attention. Knowledge of HBsAg prevalence, correlates of chronic HBV infection, in addition to risks of a range of liver and non-liver diseases, is needed to facilitate increased screening, diagnosis and management of individuals with chronic HBV.

Authors: Hamilton, EM

• DOI: 10.5287/ora-6rrrrn97g
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: chronic hepatitis b; cancer; stroke; risk factors; burden of disease; China; epidemiology
• Subjects: Population health; Burden of disease; Statistics; Epidemiology