THE IC3 TRIAL: Identifying Cirrhosis and liver Cancer in primary Care

Following consent, both groups will have a brief discussion about lifestyle factors to reduce risk of cirrhosis and liver cancer (approx. 3-5 mins). During this discussion participants will be provided with an information leaflet about liver health (developed from recommendations in 1-3’). This informational brochure is designed as a credible ‘attention control’ while not altering ‘usual care’ since it is unlikely to prompt discussions about cirrhosis/HCC risk or screening with their GP. It also increases engagement in the trial for control participants to minimise attrition. Following randomisation, patients assigned to the intervention arm will enter a two-stage cirrhosis detection pathway co-ordinated by study staff. If diagnosed with a liver stiffness measure of equal to or greater than 8.0 kPa the participant will be referred by their GP to a hepatologist. At review, the participant may be entered into Hepatocellular Carcinoma (HCC) surveillance by the specialist. This surveillance pathway will become part of normal specialist care' conducted under the guidance of the local Hepatologist and supported by the trials team. This model of care reflects the efficacy design of our clinical trial and could be readily implemented in the future into a GP practice team with a practice or community nurse case worker. Two-stage Cirrhosis Detection Pathway: Participants will initially undergo a non-fasting blood test at a Sonic pathology laboratory. FIB4 will be calculated from standard of care blood tests performed locally with serum then forwarded to Pathwest for Hepascore analysis. Results will be available within two weeks. We anticipate 25% of the intervention arm will have high readings of either serum biomarker (FIB-4 >1.30 or Hepascore greater than or equal to 0.60). All intervention participants will be contacted with their results, with those who have an elevated screening test to undergo a Fibroscan (liver stiffness measure). This will be performed at the GP practice by trained research staff. Fibroscan (Echosens, France) will be performed on portable calibrated machines using a standardized protocol and validated quality control criteria as per the manufacturer recommendations. Those with an elevated reading (greater than or equal to 8 kPa), changed in October 2022 to bring in line with current guidelines, will be referred by their GP to a hepatologist. The specialist will determine, whether they will be entered into HCC surveillance (defined as two liver diagnostic imaging with or without serum AFP levels in a 12 month period. Patients with an unreliable Fibroscan (anticipated <5%) will be referred for specialist review. All referred patients will be followed to see if they are enrolled into HCC surveillance or discharged back to GP care. HCC Surveillance Program: Participants will receive written appointment times and text message reminders for surveillance imaging and serum testing, which will be performed at local radiology and pathology providers respectively, ideally, twice within a 12 (+/-2) month period. Missed appointments or testing will be followed-up by phone by study staff with a re-appointment and discussion about the importance of surveillance provided. This approach has been demonstrated to be effective in capturing 79% of early HCC in community-based surveillance. There is no set 'total period' for HCC surveillance - the period will be determined by clinical relevance and will be managed by a hepatologist or GP or both. 1. Gofton, C., & George, J. (2021). Updates in fatty liver disease: Pathophysiology, diagnosis and management. Australian Journal of General Practice, 50(10), 702-707. 2. Nobili, V., Carter-Kent, C., & Feldstein, A. E. (2011). The role of lifestyle changes in the management of chronic liver disease. BMC medicine, 9(1), 1-7. 3. Beg, S., Curtis, S., & Shariff, M. (2016). Patient education and its effect on self-management in cirrhosis: a pilot study. European journal of gastroenterology & hepatology, 28(5), 582-587.