Trends in cause-specific mortality among people with hepatitis C virus in New South Wales, Australia

BACKGROUND: Monitoring of HCV-related morbidity and mortality is crucial to evaluate direct-acting antiviral (DAA) therapy impact and HCV elimination progress. This population-based study examined mortality among individuals with an HCV notification in New South Wales (NSW), Australia, including cause-specific mortality prior to and during the viral hepatitis elimination era (2015-2021). METHODS: HCV notifications in NSW, Australia (1995-2021) were linked to hospitalisation records and cause-specific mortality records. Over the period 2002-2021, all-cause and cause-specific mortality rates were examined. Cox proportional hazard models were used to assess factors associated with mortality during the viral hepatitis elimination era. RESULTS: Among people with HCV notifications in 1995-2021, 112,046 were alive during 2002-2021 and contributed to mortality analyses. All-cause mortality per 100,000 population increased from 5.5 in 2002 to 13.4 in 2015 and plateaued at 12.9 in 2021. Liver-related mortality per 100,000 population increased from 2.0 in 2002 to 5.9 in 2015, before declining to 4.6 in 2021. Drug-related mortality per 100,000 population increased from 0.7 in 2002 to 1.8 in 2015, before declining to 1.2 in 2021. Factors associated with increased mortality risk during 2015-2021 included: recent injecting drug use (adjusted Hazard Ratio [aHR] 7.22, 95 % CI 6.84-7.62) and recent alcohol use disorder (aHR 3.17, 95 % CI 2.97-3.37). Recent opioid agonist therapy (aHR 0.47, 95 % CI 0.43-0.51) and recent incarceration (aHR 0.32, 95 % CI 0.23-0.45) were associated with lower mortality risk. CONCLUSION: During the HCV elimination era, both liver-related and drug-related mortality have declined, suggesting direct and indirect impacts of DAA therapy, respectively. Expanded opioid agonist therapy coverage and enhanced alcohol use disorder management could further reduce mortality.