Danielle Adebayo1, Vincenzo Morabito1, Fausto Andreola1, Giulia Pieri2, Tu-Vin Luong3, Amar Dhillon3, Rajeshwar Mookerjee1, Rajiv Jalan1. 1. Liver Failure Group, Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK. 2. Sheila Sherlock, Liver Center and UCL, Institute of Liver and Digestive Health, Royal Free Hospital, London, UK. 3. Department of Cellular Pathology, Royal Free Hospital NHS Foundation Trust, London, UK.
Abstract
BACKGROUND & AIMS: Mortality of patients who develop acute-on-chronic liver failure (ACLF) is unacceptably high but the predominant mode of cell death is unknown. The aim of this study was to evaluate whether plasma levels of caspase-cleaved cytokeratin M30 (marker of apoptosis) and uncleaved cytokeratin M65 (marker of total cell death) are altered in ACLF patients and relate this to liver histology. METHODS: Twenty-seven patients with acute decompensation of liver disease were divided into two groups: no-ACLF (n = 11) or ACLF (n-16). Healthy controls (n = 8) and acute liver failure (ALF) patients (n = 10) were also enrolled. Cell death was assessed in plasma using an ELISA kit (M30 and M65). Simultaneous biopsy samples were analysed for M30 and caspase-3 staining. RESULTS: Plasma M30 value was significantly elevated in ACLF patients compared with healthy volunteers (P = 0.0001), it was also significantly higher in ACLF patients compared with no-ACLF patients (P = 0.002). M65 levels were higher in ALF compared with ACLF patients (P = 0.002) but the apoptotic index defined by M30/M65 ratio was significantly higher in ACLF patients. Patients with extra-hepatic failure had higher M30 levels compared with patients without organ failure (P = 0.03). M30 staining in liver was more marked in the patients with ACLF and was observed in all the patients that died. CONCLUSIONS: The results of this study suggest that hepatocyte apoptosis is the predominant mode of cell death in ACLF, which can be identified in the peripheral blood. Further studies are required to validate our findings and to determine whether M30 can be used as a biomarker of apoptosis or as a target for therapy.
BACKGROUND & AIMS: Mortality of patients who develop acute-on-chronic liver failure (ACLF) is unacceptably high but the predominant mode of cell death is unknown. The aim of this study was to evaluate whether plasma levels of caspase-cleaved cytokeratin M30 (marker of apoptosis) and uncleaved cytokeratin M65 (marker of total cell death) are altered in ACLF patients and relate this to liver histology. METHODS: Twenty-seven patients with acute decompensation of liver disease were divided into two groups: no-ACLF (n = 11) or ACLF (n-16). Healthy controls (n = 8) and acute liver failure (ALF) patients (n = 10) were also enrolled. Cell death was assessed in plasma using an ELISA kit (M30 and M65). Simultaneous biopsy samples were analysed for M30 and caspase-3 staining. RESULTS: Plasma M30 value was significantly elevated in ACLF patients compared with healthy volunteers (P = 0.0001), it was also significantly higher in ACLF patients compared with no-ACLF patients (P = 0.002). M65 levels were higher in ALF compared with ACLF patients (P = 0.002) but the apoptotic index defined by M30/M65 ratio was significantly higher in ACLF patients. Patients with extra-hepatic failure had higher M30 levels compared with patients without organ failure (P = 0.03). M30 staining in liver was more marked in the patients with ACLF and was observed in all the patients that died. CONCLUSIONS: The results of this study suggest that hepatocyte apoptosis is the predominant mode of cell death in ACLF, which can be identified in the peripheral blood. Further studies are required to validate our findings and to determine whether M30 can be used as a biomarker of apoptosis or as a target for therapy.
Authors: Sara Blasco-Algora; José Masegosa-Ataz; María Luisa Gutiérrez-García; Sonia Alonso-López; Conrado M Fernández-Rodríguez Journal: World J Gastroenterol Date: 2015-11-14 Impact factor: 5.742
Authors: Gautam Mehta; Sam Rousell; Gary Burgess; Mark Morris; Gavin Wright; Stuart McPherson; Catherine Frenette; Matthew Cave; David T Hagerty; Alfred Spada; Rajiv Jalan Journal: J Clin Exp Hepatol Date: 2017-11-22
Authors: Mark J W McPhail; Debbie L Shawcross; Matthew R Lewis; Iona Coltart; Elizabeth J Want; Charalambos G Antoniades; Kiril Veselkov; Evangelos Triantafyllou; Vishal Patel; Oltin Pop; Maria Gomez-Romero; Michael Kyriakides; Rabiya Zia; Robin D Abeles; Mary M E Crossey; Wayel Jassem; John O'Grady; Nigel Heaton; Georg Auzinger; William Bernal; Alberto Quaglia; Muireann Coen; Jeremy K Nicholson; Julia A Wendon; Elaine Holmes; Simon D Taylor-Robinson Journal: J Hepatol Date: 2016-01-18 Impact factor: 25.083