Trends in the Mortality of Hepatocellular Carcinoma in the United States

Primary liver cancer mortality rates have been increasing in the US, but reported decreases among 35-49 year olds may foreshadow future declines. We sought to use age-period-cohort (APC) modeling to evaluate the contribution of cohort effects to hepatocellular carcinoma (HCC) mortality trends in the US. Data on HCC mortality were obtained from the Centers for Disease Control and Prevention National Center for Health Statistics WONDER Online Multiple Cause of Death database, 1999-2015. Crude mortality rates were plotted by gender and age at death. Gender-specific restricted cubic spline APC models were fit to determine influence of birth cohort on incidence of HCC mortality, in reference to the 1940 birth cohort. Highest mortality rates were found among men ages 70+, with steepest increase in mortality observed among men 55-69 years old. Similar trends were found among females. Accounting for the cohort effect in the APC model markedly improved model fit (likelihood ratio test p < 0.001). Relative to the 1940 birth cohort, risk of mortality due to HCC was significantly higher in later as well as earlier cohorts. HCC-associated mortality continues to increase, secondary to an increase in the risk of HCC-associated mortality in more recent birth cohorts among both men and women.