Association of Nationwide Hepatitis B Vaccination and Antiviral Therapy Programs With End-Stage Liver Disease Burden in Taiwan

IMPORTANCE: Chronic infections of hepatitis B and C viruses are the main causes of end-stage liver disease (ESLD) worldwide. The successful control of viral hepatitis is critical to reducing the burden of ESLD. OBJECTIVE: To examine the association of 2 world-first nationwide neonatal hepatitis B vaccinations and national antiviral therapy programs implemented in Taiwan (in 1984 and 2003, respectively) with the burden of ESLD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included children and adults aged 5 to 39 years from the National Cancer Registry Database and the National Death Registry Database between 1979 and 2018 in Taiwan. Individuals who died from chronic liver disease (CLD) and cirrhosis and hepatocellular carcinoma (HCC) or were diagnosed with HCC were included for analysis. Analyses were performed in January 2021. MAIN OUTCOMES AND MEASURES: The main outcomes were measures of age, period, and cohort associations with CLD mortality and HCC incidence and mortality using an age-period-cohort analysis. RESULTS: Among the 43 604 individuals (mean [SD] age, 33.3 [6.0] years; 37 755 men [86.6%]) with ESLD in the cohort, there were 17 904 CLD deaths, 11 504 HCC deaths, and 14 196 HCC incident events. There was a significant increase in all 3 disease burdens after age 20 years. From 2004 to 2018, CLD mortality decreased by 26% (adjusted rate ratio [aRR], 0.74; 95% CI, 0.70-0.82), HCC mortality decreased by 50% (aRR, 0.50; 95% CI, 0.45-0.58), and HCC incidence decreased by 53% (aRR, 0.47; 95% CI, 0.44-0.52). A sharply declining association by cohort was observed from the 1982 to 1986 birth cohort to the 2007 to 2011 birth cohort, during which CLD mortality decreased by 82% (aRR, 0.18; 95% CI, 0.00-1.13), HCC mortality decreased by 63% (aRR, 0.37; 95% CI, 0.09-0.68), and HCC incidence decreased by 80% (aRR, 0.20; 95% CI, 0.00-0.48). The associations of age, period, and cohort were similar between male and female individuals and between urban and rural areas. The percentage of chronic hepatitis B infections in patients with HCC decreased from 83.3% (95% CI, 79.7%-86.5%) for those born from 1980 to 1984 to 55.6% (95% CI, 21.2%-86.3%) (from 2000 to 2004). CONCLUSIONS AND RELEVANCE: These findings suggest that the national hepatitis B vaccination program and the antiviral therapy program jointly were associated with substantial reductions in the burden of ESLD in Taiwan.