Gananandan, Kohilan;
(2025)
Novel biomarkers for predicting outcomes in patients with decompensated cirrhosis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Decompensated cirrhosis is associated with a high morbidity and mortality. Whilst prognostic scoring systems have emerged over time, these often underperform, and are solely focussed on predicting mortality. Given the onset of decompensation drastically worsens prognosis, there is an urgent unmet need for new biomarkers to predict decompensation, with the aim of preventing this. This thesis first emphasises this requirement by demonstrating the deleterious effects of the COVID-19 pandemic on the outcomes of patients with decompensated cirrhosis at a tertiary hepatology centre. Through a subsequent systematic review and meta-analysis, the current state of biomarker research in this field is evaluated, highlighting strengths but limitations thus far. The bulk of the thesis then goes on to evaluate a range of biomarkers based on the pathophysiological mechanisms underlying decompensation. Metabolic dysfunction is first investigated, with low density lipoprotein demonstrating an ability to independently predict readmissions following acute decompensation, whilst fat mass is demonstrated to be a potential nutritional biomarker that can successfully be monitored remotely using bioimpedance analysis. A second digital biomarker, an app-base cognitive test called the CyberLiver-Animal Recognition Test, is then studied, demonstrating an ability to predict re-hospitalisation due to HE, as well as provide a signal for all-cause decompensation. Finally, the last chapter evaluates the role of a novel scoring system composed of dimethylarginines which are implicated in portal hypertension and systemic inflammation. The new score exhibits an ability to independently predict acute-on-chronic liver failure development as well as readmissions. In conclusion the studies in this thesis highlight the unmet need for improved prognostic biomarkers in decompensated cirrhosis. It then systematically investigates a number of novel biomarkers, all of which demonstrate a range of beneficial features as well as significant results and therefore should be considered for inclusion in future scoring systems.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Novel biomarkers for predicting outcomes in patients with decompensated cirrhosis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211779 |
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