Liver cancer is a major contributor to the worldwide cancer burden. Incidence rates of this disease have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) accounts for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but their importance will likely decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral‐associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non‐alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcohol consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence of obesity and diabetes and controlling mycotoxin growth, are just as urgently required.

Purpose Hepatocellular carcinoma (HCC) incidence rates have been increasing in the United States for the past 35 years. Because HCC has a poor prognosis, quantitative forecasts could help to inform prevention and treatment strategies to reduce the incidence and burden of HCC. Methods Single-year HCC incident case and population data for the years 2000 to 2012 and ages 35 to 84 years were obtained from the SEER 18 Registry Database. We forecast incident HCC cases through 2030, using novel age-period-cohort models and stratifying by sex, race/ethnicity, and age. Rates are presented because absolute numbers may be influenced by population increases. Results Rates of HCC increased with each successive birth cohort through 1959. However, rates began to decrease with the 1960 to 1969 birth cohorts. Asians/Pacific Islanders (APIs) have had the highest HCC rates in the United States for many years, but the rates have stabilized and begun to decline in recent years. Between 2013 and 2030, rates among APIs are forecast to decline further, with estimated annual percentage changes of −1.59% among men and −2.20% among women. Thus, by 2030, Asians are forecast to have the lowest incidence rates among men, and Hispanics are forecast to have the highest rates among men (age-standardized rate, 44.2). Blacks are forecast to have the highest rate among women (age-standardized rate, 12.82). Conclusion Although liver cancer has long had some of the most rapidly increasing incidence rates, the decreasing rates seen among APIs, individuals younger than 65 years, and cohorts born after 1960 suggest that there will be declines in incidence of HCC in future years. Prevention efforts should be focused on individuals in the 1950 to 1959 birth cohorts, Hispanics, and blacks.

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Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.Additional Supporting Information may be found in the online version of this article.

Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence.

Our reporting of a projected increase in PLC incidence to 2030 in 30 countries serves as a baseline for anticipated declines in the longer term through the control of hepatitis B virus and hepatitis C virus infections by vaccination and treatment; however, the prospect that rising levels of obesity and its metabolic complications may lead to an increased risk of PLC that potentially offsets these gains is a concern. (Hepatology 2017).

ObjectivesIntrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinomas are rare tumors that arise from the epithelial cells of the bile ducts, and the etiology of both cancer types is poorly understood. Thus, we utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare resource to examine risk factors and novel preexisting medical conditions that may be associated with these cancer types.MethodsBetween 2000 and 2011, 2,092 ICC and 2,981 ECC cases and 323,615 controls were identified using the SEER-Medicare database. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsNon-alcoholic fatty liver disease was associated with approximately 3-fold increased risks of ICC (OR = 3.52, 95% CI: 2.87–4.32) and ECC (OR = 2.93, 95% CI: 2.42–3.55). Other metabolic conditions, including obesity and type 2 diabetes, were also associated with increased risks of both cancer types. Smoking was associated with a 46% and 77% increased ICC and ECC risk, respectively. Several autoimmune/inflammatory conditions, including type 1 diabetes and gout, were associated with increased risks of ICC/ECC. As anticipated, viral hepatitis, alcohol-related disorders, and bile duct conditions were associated with both cancer types. However, thyrotoxicosis and hemochromatosis were associated with an increased risk of ICC but not ECC, but did not remain significantly associated after Bonferroni correction.ConclusionsIn this study, risk factors for ICC and ECC were similar, with the exceptions of thyrotoxicosis and hemochromatosis. Notably, metabolic conditions were associated with both cancer types. As metabolic conditions are increasing in prevalence, these could be increasingly important risk factors for both types of cholangiocarcinoma.

These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.