Abstract
BackgroundChronic 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). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS).MethodsIn a cohort of 95,126 we performed a case-control study measuring ELF in blinded samples from 173 participants with self-reported high alcohol use and / or BMI ≥25 kg/m2 comprising all 58 cases who developed LRE and 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8.5 years.ResultsUsing Cox regression at an ELF threshold of 10.51 hazard ratios (HR) for LRE were 4.88 (95% confidence interval (CI) 2.37–10.03) (unadjusted model) and 4.62 (95% CI 2.12–10.08) (adjusted for deprivation and self-reported hypertension, heart disease, hypercholesterolaemia and diabetes). At a threshold of 9.8 HR for LRE were 2.21 (95% CI 1.22–3.97) (unadjusted model) and 2.18 (95% CI 1.19–4.01) (adjusted). ELF was evaluated as a time dependent variable by generating time-dependent Cox models; HRs at an ELF threshold of 10.51 were 1.94 (95% CI 1.10–3.39) (unadjusted) and 2.05 (95% CI 1.16–3.64) (adjusted) and at a threshold of 9.8 HRs were 1.85 (95% CI 1.09–3.15) (unadjusted) and 1.80 (95% CI 1.04–3.13) (adjusted). Area under the receiver operating characteristic curve for recruitment ELF predicting LRE was 0.58 (95% CI 0.49–0.68), and for second subsequent ELF 0.61 (95% CI 0.52–0.71).ConclusionThis study demonstrates the association between ELF and CLD in postmenopausal women with risk factors for liver disease, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the potential of ELF as a prognostic tool in health checks in primary care.Trial registrationThis study is nested in UKCTOCS. UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Registered 06/04/2000.
Highlights
Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit lifesaving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI)
We have previously described the association between increasing body mass index (BMI) and liverrelated events (LRE) in a large cohort of women participating in the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS) [10]
In the present study we aimed to investigate the association of the Enhanced Liver Fibrosis (ELF) test with liver-related events (LRE) in postmenopausal women with risk factors comprising high BMI and / or high alcohol consumption in a case-control study using the PRoBE design [11]
Summary
Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit lifesaving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS). Due to the rising prevalence of chronic liver disease (CLD), in particular driven by non-alcoholic fatty liver disease (NAFLD) and obesity, there is much potential in targeted case-finding strategies in the community in an attempt to identify liver disease. The algorithm was initially derived from a cohort of individuals with CLD with a range of aetiologies [3]
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