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Abstract
Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major causes of hepatocellular carcinoma (HCC). Improved HBV and HCV antiviral therapy may have impacted the burden, the individual risk and survival following HCC.
Aims: This thesis aimed to evaluate 1) Trends in incidence; and 2) All-cause survival following HCC in people with HBV or HCV notification; 3) Determinants of HCC survival in patients with untreated HCV in the pre-DAA era; and 4) Risk of HCC occurrence and recurrence following HCV antiviral sustained virological response (SVR, cure).
Methods: In chapters two and three, population-level data on HBV and HCV notifications in NSW (1993-2012) were linked to the NSW hospitalization database (2000-2014), NSW cancer registry (2000-2009) and NSW death registry. In chapter four, patient-level data was obtained through a prospective cohort of patients diagnosed with HCV-related HCC at a national level centre in Egypt (2013-2016). In chapter five, study-level data was obtained through a systematic review, meta-analysis and meta-regression analyses of HCC occurrence and recurrence following HCV therapy (2000-2017).
Key findings: 1) Individual-level risk of HBV-related HCC declined and HCV-related HCC risk did not change; 2) The population-level burden of HBV-HCC stabilized and HCV-HCC burden increased; 3) All-cause survival following HBV-HCC improved; while HCV-HCC survival did not improve; 4) Child-Pugh score was a key determinant of survival, even following adjustment for HCC stage and management; 5) In patients with HCV-related cirrhosis, SVR was associated with reduced risk of HCC occurrence; 6) In patients who received curative HCC treatment, SVR was associated with reduced risk of HCC recurrence and; 7) Direct-acting antiviral (DAA) and interferon (IFN)-based cure had a similar impact on HCC occurrence or recurrence risk.
Conclusion: HBV-related HCC burden has declined in NSW, suggesting an impact of more effective antiviral therapy over the study period and earlier HCC diagnosis. In contrast, the burden of HCV-HCC has escalated in the pre-DAA era, suggesting no impact of IFN-based therapy at the population level. There is no evidence to support higher risk of HCC occurrence or recurrence following HCV treatment with DAA therapy. HCV cure is associated with reduced risk of HCC regardless of type of HCV treatment.