Enhanced Liver Fibrosis Test Predicts Liver-Related Outcomes in Postmenopausal Women with Risk Factors - A Case Control Study Nested within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Background: Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit life-saving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). We evaluated performance of the Enhanced Liver Fibrosis (ELF) test in predicting CLD in postmenopausal women with risk factors in a nested case control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS). Methods: ELF was measured in blinded samples from 58 participants with selfreported high alcohol use and/or BMI ≥25kg/m2 who developed liver-related events (LRE) (cases), and in 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8*5 years. Findings: Using Cox regression at an ELF threshold of 9*8 hazard ratio (HR) for LRE was 2*21 (unadjusted model) and 2*18 (adjusted for deprivation and selfreported hypertension, heart disease, hypercholesterolaemia or diabetes). At a threshold of 10*51, HR was 4*88 (unadjusted) and 4*62 (adjusted). ELF was evaluated as a time dependent variable by generating timedependent Cox models; HRs at an ELF threshold of 9*8 were 1*85 (unadjusted) and 1*80 (adjusted), and at a threshold of 10*51 HRs were 1*94 (unadjusted) and 2*05 (adjusted). Interpretation: This study demonstrates that the ELF test predicts complications of CLD in postmenopausal women with risk factors, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the possible role for ELF as a prognostic tool in health checks in primary care. Funding Statement: No external funding for this nested study. The trial, UKCTOCS, was funded by Medical Research Council (G9901012 and G0801228), Cancer Research UK (C1479/A2884), and the UK Department of Health, with additional support from The Eve Appeal. UM and WMR are supported by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre. SA was funded by Abcodia Pvt Ltd. Declaration of Interests: UM has stocks awarded to her by UCL in Abcodia Pvt. Ltd. WMR is an inventor of the ELF test and has received fees from Siemens Healthineers for lecturing, travel, and consulting and research support. All the other authors declare no conflict of interest. Ethics Approval Statement: The current study was approved by the National Research Ethics Service (NRES) Committee London - Bentham (Ref: 05/Q0505/57) on 10th August 2011.