Circulating levels of soluble receptor for advanced glycation end products and ligands of the receptor for advanced glycation end products in patients with acute liver failure
Giuseppina Basta, Serena Del Turco, Teresa Navarra, William M Lee, Acute Liver Failure Study Group, William M Lee, Iris Liou, Jeffrey Crippin, Oren Fix, Lawrence Liu, Timothy M McCashland, J Eileen Hay, Natalie Murray, Obaid Shakil Shaikh, Daniel R Ganger, Atif Zaman, Steven Han, Eugene Schiff, Robert Fontana, Michael Schilsky, M D Cary A Caldwell, Brendan McGuire, Raymond T Chung, Don C Rockey, Robert Brown, M Edwyn Harrison, Adrian Reuben, Santiago J Munoz, K Rajender Reddy, Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Timothy Davern, A James Hanje, Jody C Olson, Ram Subramanian, Constantine J Karvellas, Giuseppina Basta, Serena Del Turco, Teresa Navarra, William M Lee, Acute Liver Failure Study Group, William M Lee, Iris Liou, Jeffrey Crippin, Oren Fix, Lawrence Liu, Timothy M McCashland, J Eileen Hay, Natalie Murray, Obaid Shakil Shaikh, Daniel R Ganger, Atif Zaman, Steven Han, Eugene Schiff, Robert Fontana, Michael Schilsky, M D Cary A Caldwell, Brendan McGuire, Raymond T Chung, Don C Rockey, Robert Brown, M Edwyn Harrison, Adrian Reuben, Santiago J Munoz, K Rajender Reddy, Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Timothy Davern, A James Hanje, Jody C Olson, Ram Subramanian, Constantine J Karvellas
Abstract
Animal studies suggest that receptor for advanced glycation end products (RAGE)-dependent mechanisms contribute to acetaminophen-induced liver damage. We examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) or RAGE ligands, including extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE), high-mobility group box 1 (HMGB1), and Nε-(Carboxymethyl)lysine adducts (CML), could aid in prognostication after an acetaminophen overdose. Sixty well-characterized acetaminophen-related acute liver failure (ALF) patients (30 spontaneous survivors and 30 patients who underwent transplantation and/or died) who were enrolled in the National Institutes of Health-sponsored Acute Liver Failure Study Group, were matched by age, met standard criteria for encephalopathy, and had an international normalized ratio > 1.5 were retrospectively studied. HMGB1, EN-RAGE, CML, and sRAGE were detected by enzyme-linked immunosorbent assay methods in sera from ALF patients and 30 healthy controls. Levels of sRAGE, EN-RAGE, and HMGB1 (but not CML) were significantly greater (P < 0.001) in ALF patients versus normal controls. The levels of sRAGE, HMGB1, and EN-RAGE were significantly higher (P = 0.03, P < 0.01, and P = 0.03) in patients with a systemic inflammatory response syndrome (SIRS) score > 2 versus patients with a SIRS score ≤ 2. Nevertheless, only sRAGE levels were significantly higher in patients who underwent transplantation and/or died versus spontaneous survivors (P < 0.001), and they were positively associated with conventional markers of liver disease severity. Multivariate logistic regression identified an encephalopathy grade > 2 as an independent predictor of an adverse outcome on admission (odds ratio, 13; 95% confidence interval, 2.3-73; P < 0.001). The RAGE-ligand axis may interfere with liver regeneration and should be a promising objective for further research.
Conflict of interest statement
Potential conflict of interest
The authors have no conflicts of interest to disclose.
© 2015 American Association for the Study of Liver Diseases.
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Source: PubMed