Hogan, Brian John;
(2023)
The Role of Serum Markers of Angiogenesis and Fibrosis in Predicting the Presence of Portal Hypertension.
Doctoral thesis (M.D(Res)), UCL (University College London).
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Abstract
Background: Portal hypertension occurs when the venous pressure in the portal vein increases above 5mmHg. In the UK, 90% of patients with portal hypertension have liver cirrhosis as the underlying aetiology. Currently invasive techniques, either gastrointestinal endoscopy or hepatic venous pressure studies, are required to confirm the diagnosis of portal hypertension. Increased portal pressure is associated with increased clinical complications and clinically significant portal hypertension occurs when the hepatic venous pressure gradient (HVPG) rises above 10mmHg. This is associated with an increased risk of ascites, varices, and variceal bleeding. Methods: Ethical approval was obtained from the NHS Research Ethics Service and local approvals from the Royal Free Hospital Research & Innovation office. Potential participants who were having HVPG measured as part of their routine care were recruited, after giving informed consent. 100 Participants had venous samples taken from peripheral blood and from the hepatic vein during the procedure. Angiogenic Tie-2 receptor cytokines, Angiopoietin-1 and -2 were measured, along with a liver fibrosis marker, the ELF test, and these were correlated with the HPVG, with traditional markers of liver fibrosis, and with patient outcomes. Results: The Angiopoietin-2/Angiopoietin-1 ratio was elevated in patients with cirrhosis and predicted an HVPG ≥ 12 with an AUROC of 0.804 (p=0.003). The ELF test predicted an HVPG ≥ 12 with an AUROC of 0.918 (p<0.001) in patients with liver cirrhosis. Both and elevated Angiopoietin-2/Angiopoietin-1 ratio and an elevated ELF test were associated with increased short-term mortality. Conclusions: In our cohort of 100 participants, we showed that both the Angiopoietin-2/Angiopoietin-1 ratio and the ELF test correlated with HVPG and deserve further validation for their potential role as diagnostic tests to rule-out clinically significant portal hypertension. The same tests were able to predict short-term mortality and may be useful biomarkers of significant disease endpoints.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | The Role of Serum Markers of Angiogenesis and Fibrosis in Predicting the Presence of Portal Hypertension |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. 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. |
| Keywords: | Portal Hypertension, Cirrhosis |
| 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/10184208 |
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