P043 Exploratory proteomic analysis of systemic changes in ALF patients undergoing PEX

• Published in: Gut Vol. 70; no. Suppl 3; p. A32
• Main Authors: Jauniaux, Benoit, Banks, Roz, Karakantza, Marina, Kerr, Maria, Snook, Niki, Bellamy, Mark, Moore, Joanna
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 17.09.2021; BMJ Publishing Group LTD
• Subjects: Apolipoproteins; Centrifugation; Clotting; Hepatic encephalopathy; Liver diseases; Mass spectrometry; Mass spectroscopy; Paracetamol; Patients; Plasma; Plasma proteins; Proteasomes; Proteins; Proteomics; Scientific imaging; Ubiquitin
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2021-BASL.52

BackgroundAcute liver failure (ALF) is defined by hepatic encephalopathy and an International Normalised Ratio greater than 1.5 in a patient with no underlying chronic liver disease. Standard-volume Plasma Exchange (SVPEX) is an extracorporeal procedure that separates plasma constituents from the cellular blood components by centrifugation and replaces it with stored plasma. There is mounting evidence supporting the clinical use of PEX as a therapy in ALF. The primary objective of this prospective pilot-exploratory proteomic study is to investigate the broad systemic changes induced by PEX on circulating proteins in patients with ALF before and after PEX.MethodsClinical parameters were compared in paracetamol-induced ALF patients receiving PEX (n=3) and ALF patients not receiving PEX (n=4). Circulating plasma protein levels were compared via mass spectrometry in 17 plasma samples from patients receiving PEX (n=2), not receiving PEX (n=2) and healthy controls (n=2).ResultsINR and PT medians were 10% higher at baseline in the PEX group compared to ALF controls. Following the first PEX cycle, INR and PT were 20% lower than in ALF controls on day 2. On mass spectrometry, several circulating proteins increased over two-fold immediately or 12 hours following PEX, in particular clotting and complement factors and apolipoproteins. Some proteins decreased to less than 50% following PEX, with the 20S proteasomes being of particular interest.DiscussionThis study is the first broad-spectrum proteomic analysis of plasma proteins in patients with ALF during and after SVPEX. PEX may improve patient clinical parameters and prognosis by several mechanisms, including the removal of the 20S proteasomes of the ubiquitin pathway, which may have a role in inducing vascular damages and multi-organ failure. This initial analysis has highlighted the potential of proteomics to profile changes induced in PEX. This will now be extended and validated with additional patients and proteomic approaches by the end of July.