Elsevier

Journal of Hepatology

Volume 70, Issue 4, April 2019, Pages 674-683
Journal of Hepatology

Research Article
The trends in incidence of primary liver cancer caused by specific etiologies: Results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention

https://doi.org/10.1016/j.jhep.2018.12.001Get rights and content

Highlights

  • Primary liver cancer incidence is still on the rise at the global level.

  • Pronounced increases in liver cancer incidence were mostly observed in countries with high socio-demographic indexes.

  • Liver cancer has been alleviated in some regions due to the control of HBV and HCV infections.

  • HCV-related liver cancer might be an important public health issue in the near future.

Background & Aims

Liver cancer is a common malignant neoplasm worldwide. The etiologies for liver cancer are diverse and the incidence trends of liver cancer caused by specific etiologies are rarely studied. We therefore aimed to determine the pattern of liver cancer incidence, as well as temporal trends.

Methods

We collected detailed information on liver cancer etiology between 1990–2016, derived from the Global Burden of Disease study in 2016. Estimated annual percentage changes (EAPCs) in liver cancer age standardized incidence rate (ASR), by sex, region, and etiology, were calculated to quantify the temporal trends in liver cancer ASR.

Results

Globally, incident cases of liver cancer increased 114.0% from 471,000 in 1990 to 1,007,800 in 2016. The overall ASR increased by an average 0.34% (95% CI 0.22%–0.45%) per year in this period. The ASR of liver cancer due to hepatitis B, hepatitis C, and other causes increased between 1990 and 2016. The corresponding EAPCs were 0.22 (95% CI 0.08–0.36), 0.57 (95% CI 0.48–0.66), and 0.51 (95% CI 0.41–0.62), respectively. The ASR of liver cancer due to reported alcohol use remained stable (EAPC = 0.10, 95% CI −0.06–0.25). This increasing pattern was heterogeneous across regions and countries. The most pronounced increases were generally observed in countries with a high socio-demographic index, including the Netherlands, the UK, and the USA.

Conclusions

Liver cancer remains a major public health concern globally, though control of hepatitis B and C virus infections has contributed to the decreasing incidence in some regions. We observed an unfavorable trend in countries with a high socio-demographic index, suggesting that current prevention strategies should be reoriented, and much more targeted and specific strategies should be established in some countries to forestall the increase in liver cancer.

Lay summary

Liver cancer is a common malignant neoplasm worldwide. The incidence patterns of liver cancer caused by different etiologies varied considerably across the world. In this study, we aim to determine the pattern of liver cancer incidence as well as the temporal trends, thereby facilitating the establishment of more tailored prevention strategies for liver cancer.

Introduction

Liver cancer is a common lethal malignancy that afflicts in excess of 1 million people and caused 800,000 deaths globally in 2016.1 It has been well documented that the incidence of liver cancer varies considerably across the world, with the highest incidence observed in East Asia. In contrast, the incidence in America is nearly 5- to 10-fold lower than the incidence observed in East Asia.2 Recent decreases in the incidence of liver cancer have been reported in China and Japan.[3], [4], [5] However, newly diagnosed cases and the age standardized incidence rate of liver cancer have increased on a global level during the last few decades, albeit significant public health efforts have been made to counter this problem.[2], [6], [7]

The underlying etiologies for liver cancer have been extensively investigated and widely recognized in previous epidemiological studies.8 Therefore the heterogeneous incidence pattern of liver cancer was mainly determined by the prevalence of risk factors across different regions. For example, endemic hepatitis B virus (HBV) and development of chronic hepatitis B infection has been the main driver of liver cancer in China.[9], [10] Whereas in South Korea and Japan, liver cancer is mainly caused by hepatitis C virus (HCV) infection, with HBV infection only accounting for approximately 15–20% of the total cases.11 Knowing the pattern of liver cancer incidence as well as the temporal trends facilitates the initiation of more targeted prevention strategies, thereby promoting the precise prevention of liver cancer.

The Global Burden of Disease (GBD) study assessed the liver cancer burden in 195 countries and territories across the world, and provided a unique opportunity to understand the landscape of liver cancer.1 In a recent study, Akinyemiju et al. described the global landscape of primary liver cancer mortality using the data derived from the GBD Study 2015.2 In the current study, we retrieved detailed information on the incidence of liver cancer caused by 4 major etiologies from the GBD Study 2016. We further assessed the disease burden of liver cancer by determining temporal trends of liver cancer incidence caused by specific etiologies from 1990 to 2016 at global, regional, and national levels. Our results can serve as an important extension and complement to the previous study,2 while also assisting in the design of targeted strategies in liver cancer prevention tailored to different countries.

Section snippets

Study data

Annual incident cases and age standardized incidences of liver cancer from 1990 to 2016, by sex, region, country, and etiology (hepatitis B, hepatitis C, alcohol consumption, and other causes), were collected from the Global Health Data Exchange (GHDx) query tool (http://ghdx.healthdata.org/gbd-results-tool).12 Data from a total of 195 countries and territories were available. These countries and territories were then categorized into 5 regions in terms of socio-demographic index (SDI),

Global liver cancer burden

The ASR of liver cancer varies considerably across the world, with the highest ASR observed in Mongolia (108.37 per 100,000 in 2016), followed by Taiwan (China) and Gambia (Fig. 1A). As for the absolute number, more than half of newly diagnosed cancer cases were recorded in China in 2016 (570,000), followed by Japan and the USA.

Globally, the incident cases of liver cancer increased 114.0% (95% CI 108.4%–119.8%) from 471,000 in 1990 to 1,007,800 in 2016. The most pronounced increase was observed

Discussion

The heterogeneous pattern in risk factor exposures results in a markedly diverse liver cancer incidence across the world, and makes the prevention of liver cancer complex.[10], [16], [17] In the current study, we comprehensively analyzed the temporal trends in primary liver cancer (more than the hepatocellular carcinoma) incidence caused by several of the most common etiologies at the global, regional, and national level. In general, liver cancer was increased in both incidence and cancer cases

Acknowledgement

We appreciate the works by the Global Burden of Disease study 2016 collaborators. We also would like to thank Prof. Shunzhang Yu, Prof. Na He and Prof. Genming Zhao from School of Public Health, Fudan University; Prof. Jiucun Wang from School of Life Sciences, Fudan University; Prof. Weiming Ye from Karolinska Institutet; Prof. Ming Lu from Qilu Hospital of Shandong University, who provided insightful methodological advice and wisdom throughout the study.

Financial support

This work was supported by the National Key Research and Development Program of China (grant number: 2017YFC0907002, 2017YFC0907501, 2017YFC211700); the National Natural Science Foundation of China (grant numbers: 81772170, 81502870); the key basic research grants from Science and Technology Commission of Shanghai Municipality (grant number: 16JC1400500); the International S&T Cooperation Program of China (grant number: 2015DFE32790); and Shanghai Municipal Science and Technology Major Project

Conflict of interest

The authors declare no conflicts of interest that pertain to this work.

Please refer to the accompanying ICMJE disclosure forms for further details.

Authors’ contributions

Study design: TZ, XC. Data collection: ZL, HY, QF, NC. Data analyses: ZL, YJ. Results interpretations: All authors. Manuscript writing: ZL, YJ, TZ, XC, CS, HY, LJ. Manuscript proofing: TZ, XC, CS, LJ.

References (47)

  • J.M. Pawlotsky et al.

    From non-A, non-B hepatitis to hepatitis C virus cure

    J Hepatol

    (2015)
  • L. Pimpin et al.

    Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies

    J Hepatol

    (2018)
  • C.W. Lin et al.

    Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis

    J Hepatol

    (2013)
  • H. Vandenbulcke et al.

    Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: a prospective study

    J Hepatol

    (2016)
  • C. Fitzmaurice et al.

    Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 Cancer Groups, 1990 to 2016: a systematic analysis for the global burden of disease study

    JAMA Oncol

    (2018)
  • T. Akinyemiju et al.

    The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015

    JAMA Oncol

    (2017)
  • L. Bai et al.

    The trends and projections in the incidence and mortality of liver cancer in urban Shanghai: a population-based study from 1973 to 2020

    Clin Epidemiol

    (2018)
  • J. Wu et al.

    Patterns and trends of liver cancer incidence rates in Eastern and Southeastern Asian countries (1983–2007) and predictions to 2030

    Gastroenterology

    (2018)
  • H. Tanaka et al.

    Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003

    Ann Intern Med

    (2008)
  • C. Fitzmaurice et al.

    Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 Cancer Groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease study

    JAMA Oncol

    (2017)
  • C. Fitzmaurice et al.

    The global burden of cancer 2013

    JAMA Oncol

    (2015)
  • H.B. El-Serag

    Epidemiology of viral hepatitis and hepatocellular carcinoma

    Gastroenterology

    (2012)
  • J.H. Fan et al.

    Attributable causes of liver cancer mortality and incidence in China

    Asian Pac J Cancer Prev

    (2013)
  • Cited by (437)

    View all citing articles on Scopus

    These authors contributed equally to this work.

    View full text