Global trends and predictions in hepatocellular carcinoma mortality

doi:10.1016/j.jhep.2017.03.011

Journal of Hepatology

Volume 67, Issue 2, August 2017, Pages 302-309

https://doi.org/10.1016/j.jhep.2017.03.011 Get rights and content

Background & Aims

Trends in hepatocellular carcinoma (HCC) mortality rates have increased over recent decades in most countries. It is also the third cause of cancer death worldwide. The aim of this study is to update global trends in HCC mortality to 2014, and predict trends in rates in the EU, USA and Japan to 2020.

Methods

Death certification data for HCC over the 1990–2014 period from the World Health Organization database were analyzed. Sixteen European, five American countries, and six other countries worldwide were included, as well as the EU as a whole.

Results

In European men, mortality rates were stable during the last decade (3.5/100,000). HCC mortality increased in Northern and Central Europe, and decreased in Southern Europe. In the USA, HCC mortality increased by 35% between 2002 and 2012, reaching 3.1/100,000 men in 2012; it is predicted to remain stable to 2020. Reduced mortality rates were observed in East Asia, although they remained around 10–24/100,000 men. In Japan, HCC mortality is predicted to decrease (5.4/100,000 men in 2020). Trends were favorable in the young, but unfavorable in middle aged, except in East Asia. Mortality rates were 3- to 5-fold lower in women than men in most regions, but trends were similar.

Conclusions

Control of hepatitis B (HBV) and hepatitis C virus (HCV) infections has contributed to the decrease in HCC-related mortality in East Asia and Southern Europe. Unfavorable trends in other regions can be attributed to HCV (and HBV) epidemics in the 1960s and 1980s, alcohol consumption, increased overweight/obesity, and diabetes. Better management of cirrhosis, HCC diagnosis and treatment are also influencing the mortality trends worldwide.

Lay summary

Mortality rates due to HCC have increased in many countries over recent decades. In this study, we updated worldwide mortality trends for HCC from 1990 to 2014, and predicted trends for some countries to 2020. We observed unfavorable trends in Northern and Central Europe, North and Latin America. East Asia showed an improvement, however mortality rates in this region were 2- to 5-fold higher than in most European countries and the Americas. Steady declines to 2020 are predicted for East Asia but not for Europe and the Americas.

Graphical abstract

Introduction

Primary liver cancer, and specifically hepatocellular carcinoma (HCC), is still the third cause of cancer death worldwide, with exceedingly high rates in East/Southeast Asia, several areas of Africa and, historically, southern Europe. In addition, over the last decade, liver cancer was one of the few cancer sites showing upward trends in both sexes in several countries worldwide.¹

These patterns, and the related trends, are difficult to interpret, because liver cancer is one of the most common sites for secondary tumors, and the validity of the distinction between HCC and metastatic liver cancer is variable across countries and time periods.[2], [3] Still, the fact that appreciable trends were also observed in the young and middle aged, for whom death certification is more reliable, and the observation of diverging trends in women and men in various countries indicate that these are partially or largely real.[4], [5]

Chronic infections with hepatitis B (HBV) and C viruses (HCV) are the key risk factors for liver cancer worldwide.[3], [6] Other relevant risk factors are heavy alcohol drinking,⁷ tobacco,⁸ overweight, diabetes, metabolic syndrome, aflatoxin, and selected aspects of diet.[3], [9], [10], [11], [12]

Given these complex risk factors and their differences between countries and time periods, we have updated patterns and trends in liver cancer (HCC) mortality to 2014, and predicted its trends for selected major countries to 2020.

Section snippets

Materials and methods

We retrieved official death certification data for HCC over the 1990–2014 period, from the World Health Organization (WHO) database, as available through electronic support.¹³ We included data for 16 selected European countries, five from the Americas, and another six countries worldwide, reporting consistent and hence likely reasonably valid data. We also analyzed data for the EU as a whole, including the 28 countries as of July 2013, except Cyprus, for which data only recently became

Results

Table 1 shows age-standardized mortality rates from HCC per 100,000 men, at all ages and at age 20–44 and 45–59 years, for 27 selected countries worldwide and the EU around 2002 (2000–2004) and 2012 (2011–2013), the average deaths per year of the latest triennium, and the corresponding change in rates. At all ages, mortality rates declined from 2002 to 2012 in the Czech Republic (−19.2%), Spain (−14.7%), France (−14%), and Italy (−11.8%). Mortality rates increased in the other EU countries, with

Discussion

HCC is one of the few major cancer sites showing unfavorable trends in several areas of the world over the last few decades, including the EU, North and Latin America.[1], [4], [26] Only areas with very high rates in the past, including Japan, Korea and China, showed appreciable declines in rates. Still, over the most recent years, HCC mortality was 2- to 5-fold higher in Japan, Hong Kong or Korea than in most European countries and the Americas. Steady declines to 2020 are predicted for East

Financial support

This work was supported by the Italian Association for Cancer Research (AIRC grant N. 14360) to the IRCCS – Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy, and by MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca), with a Scientific Independence of Young Researchers 2014 grant (project RBSI1465UH) to the Università degli Studi di Milano.

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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

Authors’ contributions

Study concept and design CLV, EN. Acquisition of data PB. Data analysis PB, GC, MM. Results interpretation and drafting of the manuscript PB, FT, CLV. Critical revision of the manuscript for important intellectual content: TR, CLV, MM, EN.

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Research ArticleGlobal trends and predictions in hepatocellular carcinoma mortality

Background & Aims

Methods

Results

Conclusions

Lay summary

Graphical abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Financial support

Conflict of interest

Authors’ contributions

Ann Oncol

Eur J Cancer

Best Pract Res Clin Gastroenterol

Ann Oncol

Lancet

Ann Oncol

Cancer Lett

Eur J Cancer

J Hepatol

Eur J Cancer

Eur J Cancer

Best Pract Res Clin Gastroenterol

Gastroenterology

Ann Oncol

J Hepatol

Gastroenterology

Trends in mortality from hepatocellular carcinoma in Europe, 1980–2004

Hepatology

Coffee and the risk of hepatocellular carcinoma and chronic liver disease: a systematic review and meta-analysis of prospective studies

Eur J Cancer Prev

Inflammatory potential of diet and risk for hepatocellular cancer in a case-control study from Italy

Br J Nutr

International Classification of Disease: 9th revision

International Statistical Classification of Disease and related Health Problems: 10th revision

Comparison between registries: age-standardized rates. Vol. IV. IARC Sci Publ No. 42.

Permutation tests for joinpoint regression with applications to cancer rates. (Erratum. In: Stat Med 2001;20: 655)

Stat Med

Research Article
Global trends and predictions in hepatocellular carcinoma mortality