Keywords
Hepatic failure
Mortality trends
Temporal trends
Epidemiology
Data Availability Statement
The data supporting the findings of this study are publicly available through the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, accessible at https://wonder.cdc.gov/. No proprietary or restricted datasets were used.
How to Cite
Abstract
Background: Liver cell carcinoma (LCC) and hepatic failure (HF) are significant contributors to liver-related mortality in the United States. This study assessed LCC- and HF-related mortality trends (1999–2023) using CDC WONDER data, stratified by demographics and geography.
Methods: Deaths among U.S. adults aged ≥25 years with LCC (ICD-10: C22.0) or HF (ICD-10: K72.9) as underlying or contributing causes were analyzed. AAMRs per 1,000,000 were calculated by direct standardization to the 2000 U.S. standard population. Joinpoint regression estimated annual percent changes (APCs) in AAMRs, stratified by sex (1999–2023) and race/ethnicity, urban-rural status, census region, and state (1999–2020).
Results: From 1999–2023, 22,963 adult deaths were recorded (77.6% men). Overall AAMR declined from 1999–2007 (APC: −2.4), was stable through 2017 (APC: +0.2), then fell through 2023 (APC: −3.5). Male AAMR followed a non-linear trajectory (APC: −2.1, 1999–2010; +0.7, 2010–2017; −4.4, 2017–2023); female AAMR was stable post-2006 (APC: −0.1). NH Asian or Pacific Islanders showed the steepest decline (APC: −6.7); Hispanics increased post-2010 (APC: +0.6). Metropolitan AAMR declined overall; non-metropolitan AAMR increased (APC: +1.3). The West had the highest regional AAMR (5.6 per 1,000,000); Hawaii the highest state-level AAMR (10.3 per 1,000,000).
Conclusion: LCC- and HF-related mortality declined overall, with descriptive subgroup variation by sex, race/ethnicity, urbanization, and geography. Targeted screening, hepatitis management, and equitable healthcare access are needed to address these patterns.
References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249. PMID: 33538338. https://doi.org/10.3322/caac.21660
2. Stravitz RT, Lee WM. Acute liver failure. Lancet. 2019;394(10201):869–881. PMID: 31498101; PMCID: PMC10836844. https://doi.org/10.1016/S0140-6736(19)31894-X
3. Massarweh NN, El-Serag HB. Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Control. 2017;24(3):1073274817729245. PMID: 28975830; PMCID: PMC5937247. https://doi.org/10.1177/1073274817729245
4. Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450–1462. PMID: 30970190. https://doi.org/10.1056/NEJMra1713263
5. Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999–2016: observational study. BMJ. 2018;362:k2817. PMID: 30021785; PMCID: PMC6050518. https://doi.org/10.1136/bmj.k2817
6. Friede A, Reid JA, Ory HW. CDC WONDER: a comprehensive online public health information system of the Centers for Disease Control and Prevention. Am J Public Health. 1993;83(9):1289–1294. PMID: 8395776; PMCID: PMC1694976. https://doi.org/10.2105/AJPH.83.9.1289
7. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC WONDER Database: Multiple Cause of Death, 1999–2023 [Internet]. 2025. Available from: https://wonder.cdc.gov/mcd-icd10-expanded.html. Accessed January 24, 2025.
8. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573–577. PMID: 17938396. https://doi.org/10.7326/0003-4819-147-8-200710160-00010
9. Ingram DD, Franco SJ. 2013 NCHS Urban-Rural Classification Scheme for Counties. Vital Health Stat 2. 2014;(166):1–73. PMID: 24776070.
10. Anderson RN, Rosenberg HM. Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep. 1998;47(3):1–16, 20. PMID: 9796247.
11. National Cancer Institute. Joinpoint Trend Analysis Software, Version 6.0.1 [Computer software]. Bethesda, MD: Surveillance Research Program, National Cancer Institute; 2024. Available from: https://www.cancer.gov
12. Wang F, Mubarik S, Zhang Y, Wang L, Wang Y, Yu C, et al. Long-term trends of liver cancer incidence and mortality in China, 1990–2017: a joinpoint and age-period-cohort analysis. Int J Environ Res Public Health. 2019;16(16):2878. PMID: 31408961; PMCID: PMC6719938. https://doi.org/10.3390/ijerph16162878
13. Doddi S, Salichs O, Hibshman T, Bhargava P. Trends of liver cell carcinoma mortality in the United States by demographics and geography. Curr Probl Diagn Radiol. 2024;53(2):208–214. PMID: 37891079. https://doi.org/10.1067/j.cpradiol.2023.10.007
14. Liu C, Wu J, Chang Z. Trends and age-period-cohort effects on the prevalence, incidence, and mortality of hepatocellular carcinoma from 2008 to 2017 in Tianjin, China. Int J Environ Res Public Health. 2021;18(11):6034. PMID: 34199687; PMCID: PMC8200005. https://doi.org/10.3390/ijerph18116034
15. Xiao J, Huang J, Zhang M, Zhu J, Wu G, Gao Y. Trends and forecast of hepatocellular carcinoma in Nantong, China: mortality rates from 1999 to 2011. Zhonghua Gan Zang Bing Za Zhi. 2015;23(9):663–668. PMID: 26524359; PMCID: PMC12814474. https://doi.org/10.3760/cma.j.issn.1007-3418.2015.09.006
16. Li Y, Xu A, Jia S, Huang J. Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma. Oncol Lett. 2019;17(5):4222–4228. PMID: 30988804; PMCID: PMC6447942. https://doi.org/10.3892/ol.2019.10127
17. Perez A, Anzaldua M, McCormick J, Fisher-Hoch S. High frequency of chronic end-stage liver disease and hepatocellular carcinoma in a Hispanic population. J Gastroenterol Hepatol. 2004;19(3):289–295. PMID: 14748876. https://doi.org/10.1111/j.1440-1746.2003.03277.x
18. White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology. 2017;152(4):812–820.e5. PMID: 27889576; PMCID: PMC5346030. https://doi.org/10.1053/j.gastro.2016.11.020
19. Kallwitz ER, Daviglus ML, Allison MA, Emory KT, Zhao L, Kuniholm MH, et al. Prevalence of suspected nonalcoholic fatty liver disease in Hispanic/Latino individuals differs by heritage. Clin Gastroenterol Hepatol. 2015;13(3):569–576. PMID: 25218670; PMCID: PMC4333050. https://doi.org/10.1016/j.cgh.2014.08.037
20. Mittal S, Sada YH, El-Serag HB, Kanwal F, Duan Z, Temple S, et al. Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the Veterans Affairs population. Clin Gastroenterol Hepatol. 2015;13(3):594–601.e1. PMID: 25148760; PMCID: PMC4333060. https://doi.org/10.1016/j.cgh.2014.08.013
21. Setiawan VW, Wei PC, Hernandez BY, Lu SC, Monroe KR, Le Marchand L, et al. Disparity in liver cancer incidence and chronic liver disease mortality by nativity in Hispanics: the Multiethnic Cohort. Cancer. 2016;122(9):1444–1452. PMID: 26916271; PMCID: PMC4840042. https://doi.org/10.1002/cncr.29922
22. Singh GK, Siahpush M. Widening rural-urban disparities in all-cause mortality and mortality from major causes of death in the USA, 1969–2009. J Urban Health. 2014;91(2):272–292. PMID: 24366854; PMCID: PMC3978153. https://doi.org/10.1007/s11524-013-9847-2
23. Endeshaw M, Hallowell BD, Razzaghi H, Senkomago V, McKenna MT, Saraiya M. Trends in liver cancer mortality in the United States: dual burden among foreign- and US-born persons. Cancer. 2019;125(5):726–734. PMID: 30480828; PMCID: PMC6681907. https://doi.org/10.1002/cncr.31869
24. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263. PMID: 38572751. https://doi.org/10.3322/caac.21834
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 Sardar Muhammad Imran Khan, Muneeb Khawar, Muhammad Haris Khan, Salman Ayub Jajja, Ayesha Fatima, M. Azeem Malik, Mirza M. Hadeed Khawar, Abdul Qadeer