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'Risk' genes heighten the chances of heavy drinkers developing alcoholic hepatitis

April 14, 2016

April 14, 2016, Barcelona, Spain: New research presented today at The International Liver Congress™ 2016 in Barcelona, Spain has uncovered a genetic link that explains why certain people with alcohol dependence are more susceptible to developing severe alcoholic hepatitis.

Severe alcoholic hepatitis is a serious clinical syndrome associated with high short-term mortality.1 According to the study, heavy drinkers who carry a specific variant in the PNPLA3 gene are more susceptible to developing this serious and life-threatening illness. The study also identified another important variant in the SLC38A4 gene, which is also thought to increase the risk of developing hepatitis in individuals who suffer from alcoholism.

According to the World Health Organization, Europe is the heaviest drinking region in the world in terms of the prevalence of alcohol consumption.2 Furthermore, in 2010, liver cirrhosis (scarring of the liver caused by continuous long-term liver damage) resulting from ARLD was responsible for 493,300 deaths (156,900 female deaths and 336,400 male deaths) worldwide.3

There is currently no specific medical treatment for severe alcoholic hepatitis and patients who develop cirrhosis have less than a 50% chance of living for five years if they fail to stop drinking.3

"Given that the spectrum of alcohol-related liver disease varies widely, with the majority of patients being asymptomatic, we were interested to find out why a small proportion of these people go on to develop severe alcoholic hepatitis," said Dr Stephen Atkinson, Clinical Research Fellow in Hepatology at Imperial College London and lead study author. "This first analysis of data means that we may now be able to use genetic profiles to identify people who are at increased risk of developing severe alcohol hepatitis."

The authors of the British study proposed that genetic factors contributed to the risk of developing severe alcoholic hepatitis. A two-stage genome-wide association study (GWAS) was conducted comparing people with severe alcoholic hepatitis (n=860), with alcohol dependent subjects who had no evidence of liver disease (n=1191).

The study results show that the PNPLA3 gene was associated at genome-wide significance levels as having a significant risk association with severe alcoholic hepatitis (PTHRESHOLD <5x10-8; PEXPLORATORY=1.619x10-8, OR 2.21 [95% CI 1.68 - 2.91]). The SLC38A4 gene was also identified as a risk indicator of alcoholic hepatitis (PEXPLORATORY=4.05x10-5, PREPLICATION=0.029; PMETA=4.13x10-5; OR 1.32).

"This fascinating study demonstrates the important link between genetic determination and disease severity in alcohol related liver disease," said Professor Laurent Castera, EASL Secretary General. "Having the ability to identify those who are at risk of developing a life-threatening condition is an important step forward for patients and hepatologists alike."
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Genome-wide association study (GWAS) approach

A genome-wide association study is an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Once new genetic associations are identified, researchers can use the information to develop better strategies to detect, treat and prevent the disease. Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease and mental illnesses.4

About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ takes place from April 13 - 17, 2016, at the Fira Barcelona Gran Via, Barcelona, Spain.

About EASL

Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European Association with international influence, with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact

For more information, please contact the ILC Press Office at:Onsite location reference

General session 1 and opening, Hall 6.0
Thursday 14 April, 13:30 - 15:30
Presenter: Stephen Atkinson, United Kingdom
Abstract: GS03, A genome-wide association study identifies PNPLA3 and SLC38A4 as risk loci for alcoholic hepatitis

Author disclosures of interest

None

References

1 NHS Choices. Alcohol-related liver disease. September 2015. Available from: http://www.nhs.uk/conditions/liver_disease_(alcoholic)/pages/introduction.aspx. Last accessed: March 2016.
2 European Association for the Study of the Liver. The Burden of Liver Disease in Europe. Available from: http://www.easl.eu/medias/EASLimg/Discover/EU/54ae845caec619f_file.pdf. Last accessed: March 2016.
3 Jurgen Rhem et al. Global burden of alcoholic liver diseases. Journal of Hepatology. 2013;(59):160-168.
4 National Human Genome Research Institute. Genome-Wide Association Studies. Available from: https://www.genome.gov/20019523. Last accessed: March 2016.

European Association for the Study of the Liver

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