Journal of Gastrointestinal Surgery

, Volume 21, Issue 12, pp 2033–2038 | Cite as

Trends in the Mortality of Hepatocellular Carcinoma in the United States

  • Eliza W. Beal
  • Dmitry Tumin
  • Ali Kabir
  • Dimitrios Moris
  • Xu-Feng Zhang
  • Jeffery Chakedis
  • Kenneth Washburn
  • Sylvester Black
  • Carl M. Schmidt
  • Timothy M. Pawlik
Original Article



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.


Hepatocellular carcinoma Mortality 



Alcoholic liver disease




Hepatocellular carcinoma


Hepatitis B Virus


Hepatitis C Virus


Model for end stage liver disease


Nonalcoholic steatohepatitis


Nonalcoholic fatty liver disease


United States


Compliance with Ethical Standards


All authors report no disclosures.


EWB, DT, AK, DM, XZ, JC, TMP designed the study. EWB and DT performed the data analysis. EWB, DT, AK, DM, XZ, JC, and TMP interpreted the data. EWB and DT prepared the manuscript. EWB, DT, AK, DM, XZ, JC, and TMP provided critical review.


  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Menahem B, Lubrano J, Duvoux C, Mulliri A, Alves A, Costentin C, et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: An attempt to perform an ideal meta-analysis. Liver Transpl. 2017; 23(6):836–844. doi: 10.1002/lt.24758.
  3. 3.
    Murali AR, Patil S, Phillips KT, Voigt M. Locoregional therapy with curative intent versus primary liver transplant for hepatocellular carcinoma: systematic review and meta-analysis. Transplantation. 2017; 101(8):e249–e257. doi: 10.1097/TP.0000000000001730.
  4. 4.
    Alver SK, Lorenz DJ, Marvin MR, Brock GN. Projected outcomes of 6-month delay in exception points versus an equivalent Model for End-Stage Liver Disease score for hepatocellular carcinoma liver transplant candidates. Liver Transpl. 2016; 22 (10):1343–55.CrossRefPubMedGoogle Scholar
  5. 5.
    Alver SK, Lorenz DJ, Washburn K, Marvin MR, Brock GN. Comparison of two equivalent MELD scores for hepatocellular carcinoma patients using data from the United Network for Organ Sharing liver transplant waiting list registry. Transpl Int. 2017. doi: 10.1111/tri.12967.
  6. 6.
    Ioannou GN. Transplant-related survival benefit should influence prioritization for liver transplantation especially in patients with hepatocellular carcinoma. Liver Transpl. 2017; 23(5):652–62.CrossRefPubMedGoogle Scholar
  7. 7.
    Rich NE, Parikh ND, Singal AG. Hepatocellular Carcinoma and Liver Transplantation: Changing Patterns and Practices. Curr Treat Options Gastroenterol. 2017; 15(2):296–304. doi: 10.1007/s11938-017-0133-3.
  8. 8.
    OPTN OPaTN. National Data. Organ by Status. Current U.S. Waiting List. For Type = Registrations. Based on OPTN data as of February 7. 2017. 2017. [Available from:
  9. 9.
    OPTN OPaTN. National Data, Transplants by Donor Type, U.S. Transplants Performed January 1, 1988 - December 31, 2016, For Organ = Liver. 2017 [Available from:
  10. 10.
    OPTN OPaTN. National Data. Removal Reasons by Year. Removed from the waiting list January 1, 1995 - December 31, 2016. For Organ = Liver. Based on OPTN data as of February 7, 2017. 2017. [Available from:
  11. 11.
    Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014; 109(4):542–53.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Park J, Jee YH. Age-Period-Cohort Analysis of Liver Cancer Mortality in Korea. Asian Pac J Cancer Prev. 2015; 16 (18):8589–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Tzeng IS, Lee WC. Forecasting hepatocellular carcinoma mortality in Taiwan using an age-period-cohort model. Asia Pac J Public Health. 2015; 27(2):NP65–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Akita T, Ohisa M, Kimura Y, Fujimoto M, Miyakawa Y, Tanaka J. Validation and limitation of age-period-cohort model in simulating mortality due to hepatocellular carcinoma from 1940 to 2010 in Japan. Hepatol Res. 2014; 44(7):713–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Bertuccio P, Turati F, Carioli G, Rodriguez T, La Vecchia C, Malvezzi M, et al. Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol. 2017.Google Scholar
  16. 16.
    Statistics. C-NCfDCaPNCfH. Multiple Cause of Death 1999–2015 on CDC WONDER Online Database, Released December 2016.Google Scholar
  17. 17.
    Carstensen B. Age-period-cohort models for the Lexis diagram. Stat Med. 2007; 26 (15):3018–45.CrossRefPubMedGoogle Scholar
  18. 18.
    Rutherford MJ, Lambert PC, Thompson JR. Age–period–cohort modeling. The Stata Journal. 2010; 10(4):606–27.Google Scholar
  19. 19.
    Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med. 1989; 8(5):551–61.CrossRefPubMedGoogle Scholar
  20. 20.
    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):812–20.e5.CrossRefPubMedGoogle Scholar
  21. 21.
    Yang JD, Kim WR, Coelho R, Mettler TA, Benson JT, Sanderson SO, et al. Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2011; 9(1):64–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004; 127 (5 Suppl 1):S35–50.CrossRefPubMedGoogle Scholar
  23. 23.
    Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016; 36 Suppl 1:47–57.CrossRefPubMedGoogle Scholar
  24. 24.
    El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology. 2014; 60(5):1767–75.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015; 148(3):547–55.CrossRefPubMedGoogle Scholar
  26. 26.
    Prevention. CCfDCa. Morbidity and Mortality Weekly Report. State HCV Incidence and Policies Related to HCV Preventive and Treatment Services for Persons Who Inject Drugs — United States, 2015–2016. 2017. [Available from:
  27. 27.
    Prevention. CCfDCa. Surveillance for Viral Hepatitis - United States, 2015. 2017. [Available from:
  28. 28.
    Unzueta A, Cabrera R. Treatment Options in Patients Awaiting Liver Transplantation with Hepatocellular Carcinoma and Cholangiocarcinoma. Clin Liver Dis. 2017;21(2):231–51.CrossRefPubMedGoogle Scholar
  29. 29.
    Gavriilidis P, Askari A, Azoulay D. Survival following redo hepatectomy vs radiofrequency ablation for recurrent hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford). 2017; 19(1):3–9.CrossRefPubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2017

Authors and Affiliations

  • Eliza W. Beal
    • 1
  • Dmitry Tumin
    • 2
  • Ali Kabir
    • 1
  • Dimitrios Moris
    • 1
  • Xu-Feng Zhang
    • 1
    • 3
  • Jeffery Chakedis
    • 1
  • Kenneth Washburn
    • 3
  • Sylvester Black
    • 3
  • Carl M. Schmidt
    • 1
  • Timothy M. Pawlik
    • 1
    • 4
  1. 1.Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research InstituteColumbusUSA
  2. 2.Department of Anesthesiology and Pain MedicineNationwide Children’s HospitalColumbusUSA
  3. 3.Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  4. 4.Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer ResearchThe Ohio State University, Wexner Medical CenterColumbusUSA

Personalised recommendations