Liver cancer, of which hepatocellular carcinoma (HCC) is the commonest form, is a major global health problem, with 854,000 new cases and 810,000 deaths/year1. Liver cancer is the fastest rising cause of cancer death in the UK2 and it is projected that by 2030, HCC will be the 3rd leading cause of cancer deaths in the USA, surpassing breast, colorectal and prostate cancers3. One reason why mortality is so high is that the majority of HCCs are diagnosed at a late stage when treatment is not effective. The proportion of people surviving for 1 year after a stage 1 compared to a stage 4 liver cancer diagnosis decreases from 78% to 20%4. Therefore, strategies for the earlier detection of HCC are urgently required.

The risk of liver cancer is increased by viral hepatitis infections, alcohol and obesity (associated with chronic conditions such as non-alcoholic fatty liver disease), causing the immune system to attack the liver leading to scarring and liver cirrhosis. Monitoring of people with these conditions can reduce mortality but current diagnostic tests for HCC fail to detect cancer in many cases. Furthermore, only a small fraction of people with cirrhosis go on to get HCC and so better risk prediction is needed to more efficiently target surveillance to those at the highest risk of developing cancer.