Mutation that stops heavy drinkers getting cirrhosis discovered

A genetic mutation that gives protection from liver cirrhosis, even for heavy drinkers, has been found. 

The mutation is in the gene HSD17B13, which codes for an enzyme involved in lipid metabolism in the liver. The newly discovered genetic variant leads to instability and degradation of this enzyme, and is associated with a reduced risk of cirrhosis, or scarring of the liver. The study, which analysed genome data and health records from more than 46,000 people, identified HSD17B13 as a potential therapeutic target for chronic liver diseases that are not currently treatable.

Cirrhosis results from long-term liver damage, which can be due to alcohol consumption, obesity, inherited conditions or prolonged hepatitis B or C infections. The research found that people who did not have a working copy of HSD17B13 had a 73 percent lower chance of developing cirrhosis from heavy drinking. They were also half as likely to develop cirrhosis from other causes. 

The participants' protein-coding genome data and the corresponding electronic health records were evaluated for associations with serum levels of two common markers of liver health, alanine aminotransferase and aspartate aminotransferase. The researchers at Regeneron Pharmaceuticals Inc. in Tarrytown, New York, then analysed associations with chronic liver disease in these participants.

Regeneron's partners in the study included the Geisinger Health System (GHS), which operates a large hospital network in the USA. Data from GHS's MyCode Community Health Initiative was used to provide the large sample of genome data. 

'This genetic "experiment of nature" has pinpointed a new target for the discovery of novel medicines that mimic the action of this variant and similarly reduce the risk of chronic liver diseases,' said Dr Aris Baras, vice president at Regeneron and head of the Regeneron Genetics Centre, where the study was carried out.

Regeneron announced it will work with Alnylam Pharmaceuticals to create gene-silencing medicines to try to mimic the protective effect of this gene variant. In the UK, over 4000 people die from cirrhosis each year, and around 700 people require a liver transplant to survive. 

The study was published in the New England Journal of Medicine.