Alenezi, Yusef
(2024)
Biomarkers to predict advanced liver diseases.
PhD thesis, University of Nottingham.
Abstract
Background: Chronic liver disease (CLD) is one of the leading causes of morbidity and mortality, accounting for more than two million deaths annually worldwide. In recent years, Non-alcoholic Fatty Liver Disease (NAFLD) has been a fast-emerging cause of CLD, which can progress to advanced conditions such as liver cirrhosis, hepatocellular carcinoma (HCC), and liver failure. While the condition of simple steatosis in NAFLD patients is usually benign, the risk of progression to advanced CLD underscores the importance of early detection, as late diagnosis frequently leads to poor patient outcomes. As a result, considerable effort is now being made to find non-invasive methods for the early detection of CLD.
This study assesses the feasibility of using non-invasive biomarkers to predict the progression to advanced CLD. In order to achieve this, it begins by assessing the prevalence of NAFLD in the United Kingdom (UK) and the Kingdom of Saudi Arabia (KSA), and then determines the availability of non-invasive biomarkers among UK primary care patients.
Methodology: Systematic review and meta-analysis were used to assess NAFLD prevalence among the general population in the UK and KSA. Then, three retrospective cohort studies were conducted using Clinical Practice Research Datalink (CPRD) data from 1 Jan 1990 – 31 Dec 2016. The first study determined the proportion of patients over 40 with data within their records to calculate normal or abnormal liver fibrosis biomarkers. The second and third studies utilised CPRD data, comprising all cases eligible for linkage to the National Cancer Registration and Analysis Service (NCRAS) cancer registry database, ONS death registration, and Hospital Episode Statistics (HES) data to identify patients who have been diagnosed with advanced CLD and determine whether the AST/ALT ratio, APRI score, and FIB-4 index could be used to predict subsequent advanced CLD in those for whom they were assessed.
Findings: The systematic review studies showed an estimated pooled prevalence of NAFLD among disease-unrestricted populations to be 16.8% and 23.8% for KSA and the UK, respectively. There is good evidence that adults with type 2 diabetes mellitus (T2DM) have a higher prevalence of NAFLD in both countries. The CPRD findings showed that the most frequent calculable biomarker was the APRI score, followed by the AST/ALT, and the least calculable biomarker was the FIB-4. However, despite being the most calculable biomarker, the prevalence of abnormal APRI was lower than that of the other biomarkers.
The findings also demonstrated that the AST/ALT ratio, APRI score, and FIB-4 index allow for the appropriate identification of patients at a higher risk of developing advanced CLD or the outcomes of liver transplantation and, possibly, death. Notably, based on conventional cutoffs, abnormal APRI scores showed a stronger association with the development of the outcomes than the abnormal AST/ALT ratio and Fib4 index.
Conclusion: This thesis revealed a high prevalence of NAFLD among the general population in the UK and KSA. The studies in this thesis have clearly shown that abnormal biomarkers allow for the appropriate identification of patients at a higher risk of developing advanced CLD. The use of routinely collected data to measure the availability of these biomarkers reveals the potential and practicality of a large dataset for future biomarker studies.
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