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Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study

BMJ 2018; 362 doi: (Published 18 July 2018) Cite this as: BMJ 2018;362:k2817
  1. Elliot B Tapper, assistant professor12,
  2. Neehar D Parikh, assistant professor12
  1. 1Division of Gastroenterology and Hepatology, University of Michigan, MI, USA
  2. 2Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
  1. Correspondence to: EB Tapper 3912 Taubman, SPC 5362, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA etapper{at} (@ebtapper on Twitter)
  • Accepted 11 June 2018


Objective To describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region.

Design Observational cohort study.

Setting Death certificate data from the Vital Statistics Cooperative, and population data from the US Census Bureau compiled by the Center for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (1999-2016).

Participants US residents.

Main outcome measure Deaths from cirrhosis and hepatocellular carcinoma, with trends evaluated using joinpoint regression.

Results From 1999 to 2016 in the US annual deaths from cirrhosis increased by 65%, to 34 174, while annual deaths from hepatocellular carcinoma doubled to 11 073. Only one subgroup—Asians and Pacific Islanders—experienced an improvement in mortality from hepatocellular carcinoma: the death rate decreased by 2.7% (95% confidence interval 2.2% to 3.3%, P<0.001) per year. Annual increases in cirrhosis related mortality were most pronounced for Native Americans (designated as “American Indians” in the census database) (4.0%, 2.2% to 5.7%, P=0.002). The age adjusted death rate due to hepatocellular carcinoma increased annually by 2.1% (1.9% to 2.3%, P<0.001); deaths due to cirrhosis began increasing in 2009 through 2016 by 3.4% (3.1% to 3.8%, P<0.001). During 2009-16 people aged 25-34 years experienced the highest average annual increase in cirrhosis related mortality (10.5%, 8.9% to 12.2%, P<0.001), driven entirely by alcohol related liver disease. During this period, mortality due to peritonitis and sepsis in the setting of cirrhosis increased substantially, with respective annual increases of 6.1% (3.9% to 8.2%) and 7.1% (6.1% to 8.4%). Only one state, Maryland, showed improvements in mortality (−1.2%, −1.7% to −0.7% per year), while many, concentrated in the south and west, observed disproportionate annual increases: Kentucky 6.8% (5.1% to 8.5%), New Mexico 6.0% (4.1% to 7.9%), Arkansas 5.7% (3.9% to 7.6%), Indiana 5.0% (3.8% to 6.1%), and Alabama 5.0% (3.2% to 6.8%). No state showed improvements in hepatocellular carcinoma related mortality, while Arizona (5.1%, 3.7% to 6.5%) and Kansas (4.3%, 2.8% to 5.8%) experienced the most severe annual increases.

Conclusions Mortality due to cirrhosis has been increasing in the US since 2009. Driven by deaths due to alcoholic cirrhosis, people aged 25-34 have experienced the greatest relative increase in mortality. White Americans, Native Americans, and Hispanic Americans experienced the greatest increase in deaths from cirrhosis. Mortality due to cirrhosis is improving in Maryland but worst in Kentucky, New Mexico, and Arkansas. The rapid increase in death rates among young people due to alcohol highlight new challenges for optimal care of patients with preventable liver disease.


  • Contributors: Both authors conceived the study, acquired and analyzed the data, and wrote the manuscript. EBT is the guarantor.

  • Funding: EBT receives funding from the National Institutes of Health (NIH) through the Michigan Institute for Clinical and Health Research (KL2TR002241). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organization for the submitted work for NDP, whereas EBT receives funding from the National Institutes of Health (NIH) through the Michigan Institute for Clinical and Health Research (KL2TR002241); no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; outside the current work, EBT has received grants from Valeant and from Gilead and personal fees from Novartis, and NDP has received personal fees from Bristol Myers Squibb, Bayer, and Eisai, and grants from Bayer and TARGET Pharmaceuticals. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Ethical approval: Not required as this is a publically available dataset of deidentified data.

  • Data sharing: Contact the corresponding author at etapper{at} for any inquiries regarding data or analytical code.

  • Transparency: The lead author (EBT) affirms that the manuscript is a honest, accurate, and transparent account of the study bring reported; that no important aspects of the study have been omitted

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