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The Pearl clinical study will recruit 3000 patients with high-risk conditions for liver cancer with the aim of detecting liver cancer earlier as part of the Cancer Research UK-funded DeLIVER programme.

 The first patients have now been recruited to the Prospective cohort for Early detection of Liver cancer (Pearl) study. In total, this study aims to recruit 3000 individuals with cirrhosis caused by hepatitis virus B or C, alcohol or obesity, but without liver cancer from >20 hospital sites across the UK. These participants are at higher risk of developing liver cancer and will be followed over time to identify the earliest detectable indications of liver cancer and to develop new prediction models for the individual risk of liver cancer development.

Liver cancer is a major global health problem, with 905,677 cases and 830,180 deaths in 2020, and incidence is increasing. In the majority of cases, this cancer develops on a background of cirrhosis. While screening in these at-risk populations is an effective strategy for liver cancer diagnosis, current screening methods are not sufficiently sensitive and still miss many liver cancers, especially when they are very small. Since treatments are more effective when the cancer is detected earlier, improving liver cancer risk prediction and detection methods in individuals with cirrhosis would increase the survival rates.

The £2.5 million DeLIVER programme funded by Cancer Research UK is investigating new approaches for earlier liver cancer detection. Professor Ellie Barnes (Nuffield Department of Medicine) is leading a multidisciplinary team of academic, clinical and industry partners who are experts in risk prediction modelling and a range of more sensitive detection technologies, including blood- and urine-based tests and clinical imaging.

Professor Ellie Barnes, Chief Investigator for DeLIVER, said “We hope that our promising new technologies will be able to reliably detect liver cancers much earlier. We are also aiming to develop risk models that can predict which patients with cirrhosis are more likely to develop liver cancer so that in the future we can monitor these patients more closely.

To address both goals, we have set up the UK’s largest prospective cohort of individuals with cirrhosis that will be followed for several years until some of them develop liver cancer. We can then look back in time to search the data we have collected for clues that would have told us which people would develop or had already started developing liver cancer.”

After consenting to the Pearl study, participants will be followed for four years with annual sampling of blood, urine and clinical data. The DeLIVER team will apply their best performing detection technologies to these samples. They will compare the molecular, imaging and clinical data from participants who develop liver cancer during the study with participants who don’t develop cancer to identify predictive or diagnostic markers of liver cancer. Professor Will Irving (University of Nottingham), Lead of the Pearl study, “We are excited to have started recruitment for this important prospective study. The information and samples we collect over the next four years will be crucial to our goal of detecting liver cancer earlier and saving lives, and we thank all the participants and clinical teams across the UK for their involvement.” Pearl builds on the existing STOP-HCV cirrhosis cohort that was established as part of the MRC-funded STOP-HCV programme. This is the second of three clinical studies within the DeLIVER programme to start recruitment. In March 2021, we opened the DELPHI study, to gain a better understanding about

the biology of liver cancer development. The SELiNa study of patients with small liver cancers is expected to begin recruitment in the near future to allow a direct comparison between di