Trends in Mortality From Malignant Neoplasms of the Liver and Intrahepatic Bile Ducts in the United States: A Retrospective Analysis From 1999 to 2020.

BACKGROUND: Primary malignant liver tumors constitute a significant global health challenge. We conducted an analysis of mortality trends across all forms of primary liver cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and other less prevalent types, to enhance our understanding of the overall burden these cancers impose on the US population. METHOD: The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database was analyzed, and the International Classification of Diseases, 10th Revision (ICD-10), codes were utilized to identify deaths from primary malignant neoplasms of the liver from 1999 to 2020 in patients aged 25 or older. The age-adjusted mortality rates (AAMR/100,000) for the population were extracted, and trends were analyzed for age, gender, race, and year.  Result: There were a total of 445,389 deaths from primary liver cancer from 1999 to 2020. AAMR increased from 6.95 in 1999 to 10.12 in 2020. Gender analysis showed that both sexes have shown a gradual increase in AAMR over the course of years. The mean AAMR for males was 13.09 per 100,000 population (range: 12.31-13.87; SD: 1.75), which was more than twice the rate observed in females (mean: 5.45; range: 5.16-5.74; SD: 0.66). Race analysis showed that Asian or Pacific Islanders are the only race that has shown an overall decreasing trend in mortality from liver cancer, with AAMR decreasing from 15.68 in 1999 to 12.15 in 2020. Despite the decreasing trend, Asian or Pacific Islanders still have the highest mean AAMR (mean: 14.83; range: 14.21-15.46; SD: 1.41), followed by Hispanics (13.15), Black or African Americans (11.52), American Indians or Alaskan Natives (10.51), and finally Whites (8.32).  Discussion: An important aspect of understanding the disparities in mortality from primary liver cancer will be to see these disparities in the context of HCC, which accounts for 85% of primary liver malignancies. The decreasing mortality trend from primary liver cancer observed in Asians is consistent with a decreasing trend in mortality from HCC due to a decreasing incidence of hepatitis B virus (HBV). The increased mortality from primary liver cancer among males noted throughout the study period can be attributed to higher incidences of HBV and hepatitis C virus (HCV) infections, as well as greater alcohol consumption, all of which contribute to the development of HCC. Additionally, there is evidence to support that estrogens play a protective role, limiting liver inflammation and fibrogenesis and counteracting the development of HCC in females. CONCLUSION: With an increasing mortality trend from primary malignant neoplasms of the liver, further research is needed to mitigate the risk factors and advance the treatment modalities for liver cancer.