In modelled data from GBD, alcohol is the predominant aetiology of liver disease in most countries with a high prevalence of viral hepatitis B and C in Central and Eastern Europe.
SeminarBurden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies
Graphical abstract
Introduction
Europe has the largest burden of liver disease in the world,1 with the burden expected to grow across many countries. However, the current and historical epidemiology of liver disease varies between countries within Europe. For example, Finland and the UK have observed staggering increases in liver disease mortality over the last 40 years while the inverse is true for countries such as France and Italy, where liver disease mortality began declining in the 1970s and has kept falling, largely because of effective policy and population-level measures.
Differences in liver disease epidemiology occur in part because of the prevalence of modifiable risk factors, such as harmful alcohol consumption, obesity, and viral hepatitis. Worryingly, Europe has the highest per capita alcohol consumption and alcohol-related loss of disability adjusted life years of any of the global WHO regions.2 Obesity has increased markedly over the past four decades,[3], [4] and as a result, non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent liver disease in Europe.2 The prevalence of viral hepatitis is less well documented.2 Prevention of these risk factors and types of liver disease is important in order to stop progression to other forms of liver disease, such as liver cancer. Liver disease principally affects working age people. Therefore, tackling risk factors will not only impact the individual and health system, but also the economy and business sectors.
Differences in demographics, geography, and historical factors need to be considered when trying to understand the variance in liver disease risk factors, morbidity and mortality, as well as the interventions that best reduce the burden of liver disease. Importantly, liver disease risk factors are amenable to prevention and treatment, so liver disease can be reduced and deaths can be averted. Understanding the magnitude of liver disease prevalence, how and why it has changed over time, and what works to reduce the population’s risk is imperative if countries are to learn from each other and act to reduce the burden.
Section snippets
Aim
The European Association for the Study of the Liver (EASL) HEPAHEALTH project, summarised in a report, was commissioned to: i) collect and analyse data in order to best describe the burden of liver disease across 35 European countries (including all 28 European Union [EU] countries); ii) collect data on the largest, modifiable determinants of liver disease (alcohol, obesity and viral hepatitis) and describe their changes over time; and iii) review the evidence on policies or interventions that
Methods
In order to maximise comparability across countries, and to use a standardised definition of liver disease, the majority of data on the epidemiology of liver disease and its risk factors were obtained for 35 countries (see Table 1 from online databases). It was beyond the scope of this study to include all 53 World Health Organization (WHO) European Region countries. The EU-28 countries were chosen plus additional countries where the study team had particular expertise and interest Table 2.
Data collection
When insufficient data were available, additional sources of information were collected from a comprehensive review of the peer-reviewed and grey literature (that is, resources produced outside of the traditional academic publishing, such as reports from non-academic organisations) and identifying experts through the referral of other experts (“snowballing” of contacts) in the field of liver disease.
The WHO European Detailed Mortality Data5 database combined raw mortality rates for 1994 to 2015
Analysis
Data on the prevalence and mortality of liver disease, and on the distribution of the largest modifiable risk factors for liver disease were analysed to present time trends, differences across sub-regions (UN Eastern, Northern, Southern and Western regions) and individual countries within these sub-regions. The historical trends in mortality and prevalence were overlaid with plots of alcohol consumption and obesity prevalence.
A comprehensive review of PubMed, Embase, and Google Scholar was
Present situation
Data on prevalence of liver disease was collected using the GBD 2016 project data.1 The categories of liver disease present in the dataset are cirrhosis and chronic liver disease, the other being liver cancer. Cirrhosis and chronic liver disease are further broken down into four aetiologic categories: alcohol use,
Alcohol consumption and liver disease
According to the WHO, alcohol is a dose-related risk factor for more than 200 diseases. It causes 5.9% of all deaths globally and more than 25% of deaths in the age group 20–39 years.14 For most diseases including cancer and hypertension, the dose relationship is linear starting at zero, i.e. there is no safe threshold for alcohol consumption.15 Importantly, for liver disease the relationship is exponential, with very heavy drinkers or extreme drinkers comprising a large proportion of patients
The current and historical burden
The main risk factors that have been associated with NAFLD are obesity (predominantly central adiposity) as well as type 2 diabetes. The time trend in NAFLD/non-alcoholic steatohepatitis (NASH) mortality from WHO detailed data are presented (Fig. 7).5 NAFLD/NASH represents only a very small proportion of liver-related-deaths in Europe, when analysing it as the primary cause of death, although it is unlikely that these codes represent the current understanding on NAFLD or NASH.
In fact, the
Viral hepatitis-related liver disease
Overall estimates indicate that approximately 15 million people living in the EU are infected with HBV.
Liver disease epidemiology is changing and can be changed
Historical experience illustrates how rapidly trends in liver disease mortality can change in response to population-level factors.
Evidence gathered across this study presents liver disease as a complex, diverse and important disease in Europe. Very significant shifts in liver mortality have occurred since 1970. There have been up to fourfold decreases in Southern European countries as a result of decreased wine consumption. In other countries there have been increases in liver mortality of
Conclusions
The progressing and increasing profile of liver disease in Europe is a concerning issue. The uncertainties in the sources of data do not detract from the overall picture of liver disease as a growing public health problem across Europe. This study highlights that the governance and public health tools to reverse this trend exist. These tools should be implemented and integrated to have a timely and significant impact on liver disease morbidity and mortality. The time for action is now.
Financial support
This work was supported by EASL funding.
Conflict of interest
Helena Cortez-Pinto received lecture and advisory board fees from Intercept, Genfit, and Gilead. Francesco Negro received a research grant from Gilead and AbbVie, and is advising Gilead, AbbVie, and Merck. Jeffrey Lazarus declares speaker fees and research grants from AbbVie, Gilead Sciences and MSD, outside of this study. The other authors declare no conflict of interest.
Please refer to the accompanying ICMJE disclosure forms for further details.
Authors’ contributions
Laura Pimpin was responsible for the overall management of the project, analysed data, designed and consolidated the scope, led the review of the literature, conducted qualitative interviews, and drafted the final report. Helena Cortez-Pinto advised on the HEPAHEALTH project and drafted the obesity/type 2 diabetes and liver disease section of the manuscript. Francesco Negro advised on the HEPAHEALTH project and drafted the viral hepatitis section of the manuscript. Emily Corbould collected,
Acknowledgements
Fiona Godfrey (EASL) for her invaluable help in coordinating this work. Jennifer Saxton, Jessica Flood and Holly Prudden (UKHF) for their work collecting, collating and analysing data and participation in the review of the literature. Center for Disease Analysis (CDA) Foundation for preparation of Polaris Observatory data.
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Collaborators: Members of the EASL HEPAHEALTH Steering Committee: Patrizia Burra, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padua, Italy; Olav Dalgard, Akershus University Hospital, Lørenskog, Norway; Goran Jankovic, Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Serbia; Jerzy Jaroszewicz, Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, Poland; Jeffrey V Lazarus, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain; Ansgar W. Lohse, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Valery Lunkov, Department of Hepatology, Vasilenko Clinic of Internal Diseases, Department of Internal Medicine, Russia; Marina Mayevskaya, Department of Internal Medicine, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia; Alexander Nersesov, National Research Institute of Cardiology and Internal Diseases, Almaty, Kazakhstan; Marieta Simonova, Department of Gastroenterology, HPB Surgery and Transplantology, Military Medical Academy, Sofia, Bulgaria.