Causes of death among patients with hepatocellular carcinoma in United States from 2000 to 2018

Background: The gains in survival outcomes of US patients with hepatocellular carcinoma (HCC) have come at the expense of developing non-cancer-related morbidities, such as cardiovascular diseases (CVDs) and infections. However, population-based data on causes of death (CODs) in patients with HCC are scarce. Methods: A cancer registry database in the United States was used to analyze the CODs among patients with HCC. Death cause distribution and standardized mortality ratios were calculated to quantify the disease-specific death burden. Results: A total of 40,094 patients with a histological diagnosis of HCC were identified from the SEER-18 database between 2000 and 2018, of which 30,796 (76.8%) died during the follow-up period. The majority of these deaths (25,153, 81.7%) occurred within 2 years after diagnosis, 13.2% (4075) occurred within 2-5 years, and 5.1% (1568) occurred after 5 years. All age groups had a lower burden of female deaths than of male deaths during the study period. With respect to CODs, 23,824 (77.4%), 2289 (7.4%), and 4683 (15.2%) were due to HCC, other cancers, and non-cancer causes, respectively. Non-cancer-related deaths were more common among older patients and those with longer latency periods since diagnosis. The major causes of non-cancer-related deaths are other infectious and parasitic diseases, including HIV and CVDs. Conclusions: CODs during HCC survivorship varied, and a growing number of survivors tended to die from causes other than HCC, with an increasing latency period since diagnosis. Comprehensive analyses of mortality patterns and temporal trends could underpin strategies to reduce these risks.