Increasing Burden of Liver Cancer Despite Extensive Use of Antiviral Agents in a Hepatitis B Virus-Endemic Population

Most mortalities from liver disease and liver cancer worldwide are attributable to hepatitis B virus (HBV) and hepatitis C virus. Despite remarkable advances in the treatment of HBV over past decades, limited population-level data are available regarding its impact on burden of liver disease and liver cancer. Mortality data from liver disease and liver cancer were obtained from the national death certificate database of Korea, an HBV-endemic country, between 1999 and 2013, and were analyzed by Joinpoint analysis. For liver disease, number of annual deaths decreased by 62.3% (95% confidence interval [CI], 62.0-62.6), crude death rate (CDR) decreased by 64.6% (95% CI, 64.3-64.9) from 21.2 to 7.5 per 100,000 population, and age-standardized death rate (ADR) declined by 75.0% (95% CI, 74.7-75.3), between 1999 and 2013. In contrast, for liver cancer, number of annual deaths increased by 17.8% (95% CI, 17.6-18.0) and CDR increased by 10.2% (95% CI, 10.0-10.4) from 20.5 to 22.6, although ADR decreased by 26.9% (95% CI, 26.6-27.2). The annual number of patients receiving oral antiviral agents against HBV increased from 1,716 to 187,226 during the study period. The increase in mean age at death from liver disease was significantly greater than that from liver cancer (8.8 vs. 6.1 years: P = 0.02). Conclusion: Marked reduction in liver disease mortality by widespread use of antiviral treatments against HBV may increase the life expectancy and number of patients at risk of developing liver cancer, inadvertently leading to increased burden of liver cancer in an HBV-endemic population. The competing nature between death from liver disease and that from liver cancer should be carefully considered in establishing a health care policy.