Abstract

Introduction: Hepatocellular Carcinoma (HCC), has a very poor prognosis and meek survival rates. Despite decades of research, a clear understanding of various causes of death among HCC patients is not well established. Identifying the causative factors helps develop targeted therapeutic regimens and formulate prophylactic measures. This study was therefore undertaken to identify various cancer and non-cancer causes of death in hepatocellular carcinoma (HCC) patients over different time periods after diagnosis, and to compare the mortality risk of each cause in HCC patients with the general population. Methods: In this retrospective cohort study, data of 67,637 HCC patients from 1975 to 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the association between different causes of death and the following variables: age, race, tumor stage at diagnosis, and treatment (surgery, chemotherapy, and radiotherapy); each according to the periods of < 1 year, 1-5 years, 5-10 years, and >10 years following the diagnosis. Standardized mortality ratios (SMRs) and their 95% confidence intervals (CIs) were calculated for cancer and non-cancer deaths in each of the mentioned periods following diagnosis. Results: Data of 67,637 patients, of whom 50,571 patients died during the follow-up period, were analyzed. Most deaths were due to HCC itself (35,535, 70.3%), followed by other cancers (3,983, 7.9%). The most common non-cancer causes of death, with higher mortality risk in HCC patients than in the general population, included infectious and parasitic diseases including HIV (2,823 patients, SMR = 105.68, 95% CI: 101.82-109.65), chronic liver disease and cirrhosis (2,719 patients, SMR = 76.56, 95% CI: 73.71,79.5), and heart diseases (1,265 patients, SMR = 2.26, 95% CI: 2.14-2.39). Conclusion: The mortality rates showed a declining trend from the high of within the first year after diagnosis to a low of 10 years after diagnosis. The leading cause of death in HCC patients remains HCC itself over all time intervals after diagnosis. The commonest non-cancer causes of death were chronic liver disease and cirrhosis, infectious and parasitic diseases including HIV, and they had varying incidences across different time intervals. HCC patients had a higher risk of chronic liver disease, cirrhosis, infectious and parasitic diseases including HIV as compared to the general population whereas mortality risk due to heart diseases among HCC patients was similar to the general population.

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