Declining US Hepatocellular Carcinoma Rates, 2014–2017
Authors: Meredith S. Shiels, Thomas R. O’Brien
Journal: Clinical Gastroenterology and Hepatology (2021)

Liver cancer is a prominent cause of cancer death in the United States.1Henley S.J. Ward E.M. Scott S. et al.Annual report to the nation on the status of cancer, part I: national cancer statistics.Cancer. 2020; 126: 2225-2249Crossref PubMed Scopus (465) Google Scholar Rates of hepatocellular carcinoma (HCC), the most common histologic subtype,2Ha J. Yan M. Aguilar M. et al.Race/ethnicity-specific disparities in cancer incidence, burden of disease, and overall survival among patients with hepatocellular carcinoma in the United States.Cancer. 2016; 122: 2512-2523Crossref PubMed Scopus (73) Google Scholar increased for decades,3Islami F. Miller K.D. Siegel R.L. et al.Disparities in liver cancer occurrence in the United States by race/ethnicity and state.CA Cancer J Clin. 2017; 67: 273-289Crossref PubMed Scopus (156) Google Scholar until recent years when rates flattened,4Rich N.E. Yopp A.C. Singal A.G. et al.Hepatocellular carcinoma incidence is decreasing among younger adults in the United States.Clin Gastroenterol Hepatol. 2020; 18: 242-248Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar and then potentially declined. Previously, we reported that US HCC rates in 2016 were 4% lower than 20155Shiels M.S. O'Brien T.R. Recent decline in hepatocellular carcinoma rates in the United States.Gastroenterology. 2020; 158: 1503-1505Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar; however, it was unclear from those data whether that finding reflected a true downward trend. Here, we examine HCC rates through 2017. Data on HCC were obtained from 21 cancer registries in the Surveillance, Epidemiology and End Results (SEER) program. Cases were identified using International Classification of Diseases for Oncology, 3rd edition, codes (site, C22.0; histology, 8170-8175). Incidence rates for 2000–2017 were age-standardized to the 2000 US population in 5-year age groups. Using Joinpoint regression, we identified statistically significant (P < .05) changes in rate trajectories and estimated annual percent changes in rates. Data on American Indian/Alaska Natives were restricted to purchased/referred care delivery areas to reduce racial misclassification. In a sensitivity analysis, delay-adjustment corrections for liver and intrahepatic bile duct cancers were applied to HCC rates to assess whether the decline was driven by reporting delays.6Midthune D.N. Fay M.P. Limin X.C. et al.Modeling reporting delays and reporting corrections in cancer registry data.J Am Stat Assoc. 2005; 100: 61-70Crossref Scopus (44) Google Scholar Overall HCC rates increased from 3.94/100,000 in 2000 to a peak of 6.83/100,000 in 2014 before declining to 6.30/100,000 in 2017. HCC incidence increased 5.71%/year during 2000–2007 and 2.54%/year during 2007–2014, but then declined 2.79%/year during 2014–2017 (Figure 1, Supplementary Table 1). HCC rates increased among men through 2015 and among women through 2013, before declining nonsignificantly. HCC trends varied substantially by registry (Supplementary Figure 1). The results were attenuated, although consistent, when accounting for delayed reporting (2014–2017; annual percent changes = -1.59; 95% confidence interval, -3.29 to 0.13). By age group, the highest HCC rates were observed in those aged ≥65 years (2017: 28.4/100,000), with rates increasing 3.58%/year during 2000–2015 before plateauing during 2015–2017. In 50–64 year olds, HCC rates increased during 2000–2012 before plateauing during 2012–2015 and then declining 9.45%/year during 2015–2017. Among 35–49 year olds, rates were stable during 2000–2006 and then declined 4.83%/year during 2006–2017. HCC rates among 20–34 year olds remained low (2017: 0.22/100,000) and relatively stable over the entire period (annual percent changes = -0.29). Among Asian/Pacific Islanders, HCC rates declined 2.17%/year during 2007–2015 and then decreased 7.52%/year during 2015–2017. Beginning in 2014, HCC rates declined 4.18%/year among Latinos and 2.56%/year among Whites, although this trend was not statistically significant among Whites. HCC rates have remained steady in Blacks since 2009. In contrast, among American Indians/Alaska Natives, HCC rates increased 4.87%/year during the entire period. After years of increasing rates, a drop in overall US HCC incidence started in 2014. This decrease began among 35–49 year olds in 2006 and among 50–64 year olds in 2015. HCC incidence has not yet declined in ≥65 year olds. In recent years, HCC incidence fell among Asian/Pacific Islanders, Latinos, and Whites, while remaining stable in Blacks and continuing to increase among American Indians/Alaska Natives. Although our work overlaps with other recent research that uses SEER data,5Shiels M.S. O'Brien T.R. Recent decline in hepatocellular carcinoma rates in the United States.Gastroenterology. 2020; 158: 1503-1505Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar,7Wong R.J. Kim D. Ahmed A. et al.Patients with hepatocellular carcinoma from more rural and lower-income households have more advanced tumor stage at diagnosis and significantly higher mortality.Cancer. 2021; 127: 45-55Crossref Scopus (16) Google Scholar,8Wong R.J. Saab S. Konyn P. et al.Rural-urban geographical disparities in hepatocellular carcinoma incidence among US adults, 2004-2017.Am J Gastroenterol. 2020; Google Scholar this study uniquely emphasizes the significant downward trend in HCC during 2014–2017. The main causes of HCC in the United States are chronic infection with hepatitis B virus or hepatitis C virus, alcohol consumption, and obesity.9Hales CM, Carroll MD, Fryar CD, et al. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief 2020(360):1–8.Google Scholar SEER does not collect information on etiologic risk factors; therefore, we can only speculate about reasons for the temporal trends and demographic differences we observed. It is unlikely that recent declines reflect changes in alcohol use or obesity, because the prevalence of these risk factors has not decreased. Baby boomers are the birth cohort with the highest hepatitis C virus prevalence.10Armstrong G.L. Wasley A. Simard E.P. et al.The prevalence of hepatitis C virus infection in the United States, 1999 through 2002.Ann Intern Med. 2006; 144: 705-714Crossref PubMed Scopus (1755) Google Scholar Upward and then downward trends among 50–64 year olds roughly correspond with movement of the cohort born in 1945–1964 through that age range. Increasing mortality in baby boomers, and the availability of more effective treatments for hepatitis B virus and hepatitis C virus, may explain recent HCC declines. Observed racial/ethnic differences in HCC rates likely reflect differences in underlying risk factors. Regional variation may reflect geographic differences in HCC etiology. Recently published studies have also shown variation in HCC rates by rural/urban status and household income.7Wong R.J. Kim D. Ahmed A. et al.Patients with hepatocellular carcinoma from more rural and lower-income households have more advanced tumor stage at diagnosis and significantly higher mortality.Cancer. 2021; 127: 45-55Crossref Scopus (16) Google Scholar,8Wong R.J. Saab S. Konyn P. et al.Rural-urban geographical disparities in hepatocellular carcinoma incidence among US adults, 2004-2017.Am J Gastroenterol. 2020; Google Scholar Cancer registry data are limited by potential delays in reporting, which can result in the appearance of lower rates in the most recent years; however, after applying delay adjustment, the trends remained consistent. In recent decades US rates decreased for a number of cancer sites1Henley S.J. Ward E.M. Scott S. et al.Annual report to the nation on the status of cancer, part I: national cancer statistics.Cancer. 2020; 126: 2225-2249Crossref PubMed Scopus (465) Google Scholar; however, HCC was a notable exception. Now, after many years of increasing incidence, HCC seems to be in decline. Future studies using databases that incorporate etiologic information, such as SEER-Medicare or managed health plans, are needed to understand trends in HCC incidence overall and differences across racial/ethnic groups. Thomas R. O'Brien presented an abstract based on these data at the American Association for the Study of Liver Diseases annual meeting. Supplementary Table 1Age-Standardized Incidence Rates, Average Annual Percent Changes, and Annual Percent Changes in Hepatocellular Carcinoma Rates, 2000–2017Incidence rates per 100,000Segment 1Segment 2Segment 3Segment 420002017YearsAPC (95% CI)YearsAPC (95% CI)YearsAPC (95% CI)YearsAPC (95% CI)Overall3.946.302000–20075.70 (4.98 to 6.43)2007–20142.54 (1.84 to 3.26)2014–2017-2.79 (-4.62 to -0.91)Age, y 20–340.190.222000–2017-0.29 (-1.60 to 1.05) 35–492.381.452000–20060.83 (-1.49 to 3.21)2006–2017-4.83 (-5.85 to -3.79) 50–648.8215.42000–20079.42 (8.25 to 10.6)2007–20124.27 (2.39 to 6.18)2012–2015-1.27 (-6.30 to 4.03)2015–2017-9.45 (-14.4 to -4.25) 65+16.028.42000–20153.58 (3.29 to 3.87)2015–20170.11 (-4.83 to 5.31)Sex Men6.5310.42000–20085.50 (4.77 to 6.23)2008–20151.71 (0.86 to 2.56)2015–2017-4.22 (-8.61 to 0.38) Women1.812.722000–20133.94 (3.42 to 4.46)2013–2017-2.20 (-4.57 to 0.23)Race/ethnicity White2.864.732000–20085.63 (4.72 to 6.55)2008–20143.12 (1.67 to 4.59)2014–2017-2.56 (-5.46 to 0.44) Black4.828.322000–20096.63 (5.32 to 7.95)2009–20170.08 (-1.01 to 1.18) Latino6.9610.02000–20065.47 (3.44 to 7.53)2006–20141.81 (0.67 to 2.97)2014–2017-4.18 (-7.65 to -0.58) API11.29.122000–20071.19 (-0.20 to 2.59)2007–2015-2.17 (-3.31 to -1.01)2015–2017-7.52 (-15.1 to 0.71) AI/AN7.5215.02000–20174.87 (3.37 to 6.39)AI/AN, American Indian and Alaska Natives; APC, annual percent changes; API, Asian/Pacific Islanders; CI, confidence interval. Open table in a new tab AI/AN, American Indian and Alaska Natives; APC, annual percent changes; API, Asian/Pacific Islanders; CI, confidence interval.