Christian Labenz1,2, Gerrit Toenges3, Yvonne Huber1,2, Michael Nagel1,2, Jens U Marquardt1,2, Jörn M Schattenberg1,2, Peter R Galle1,2, Joachim Labenz4, Marcus-Alexander Wörns1,2. 1. Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany. 2. Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany. 3. Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany. 4. Department of Internal Medicine, Diakonie Klinikum, Jung-Stilling Hospital, Siegen, Germany.
Abstract
BACKGROUND: Systemic inflammation is a driving force for the development of hepatic encephalopathy and recent studies demonstrated that elevated Interleukin-6 (IL-6) serum levels are associated with the presence of minimal hepatic encephalopathy in patients with liver cirrhosis. AIM: To test the hypothesis that IL-6 is a suitable marker to identify patients with liver cirrhosis at high risk for the development of overt hepatic encephalopathy. METHODS: 201 patients were included into this prospective cohort study and were followed for a mean time of 322 days. Covert hepatic encephalopathy was diagnosed according to the West-Haven criteria (hepatic encephalopathy grade 1) and with the portosystemic encephalopathy (PSE) test. RESULTS: The cumulative incidence of overt hepatic encephalopathy was higher in patients with IL-6 levels above the median of 9 pg/mL than in patients with IL-6 levels at or below the median (35.6% vs 1.9%, P < .001). After adjustment for covert hepatic encephalopathy, history of overt hepatic encephalopathy, C-reactive protein (CRP) and model for end-stage liver disease (MELD), IL-6 levels above the median remained independently associated with the development of overt hepatic encephalopathy. The predictive performance of IL-6 regarding the development of overt hepatic encephalopathy during the next 180 days (AUROC, 0.931) was numerically higher than that of MELD (AUROC, 0.841) or CRP (AUROC, 0.835). In patients without prior overt hepatic encephalopathy, the predictive performance of IL-6 (AUROC, 0.966) was even significantly higher than that of MELD (AUROC 0.843) or CRP (AUROC 0.850). The ideal cut-off for IL-6 in this setting was 23.5 pg/mL with a sensitivity and specificity of 89.3% and 89.5% respectively. CONCLUSION: IL-6 serum levels are closely linked to the development of overt hepatic encephalopathy in patients with liver cirrhosis.
BACKGROUND: Systemic inflammation is a driving force for the development of hepatic encephalopathy and recent studies demonstrated that elevated Interleukin-6 (IL-6) serum levels are associated with the presence of minimal hepatic encephalopathy in patients with liver cirrhosis. AIM: To test the hypothesis that IL-6 is a suitable marker to identify patients with liver cirrhosis at high risk for the development of overt hepatic encephalopathy. METHODS: 201 patients were included into this prospective cohort study and were followed for a mean time of 322 days. Covert hepatic encephalopathy was diagnosed according to the West-Haven criteria (hepatic encephalopathy grade 1) and with the portosystemic encephalopathy (PSE) test. RESULTS: The cumulative incidence of overt hepatic encephalopathy was higher in patients with IL-6 levels above the median of 9 pg/mL than in patients with IL-6 levels at or below the median (35.6% vs 1.9%, P < .001). After adjustment for covert hepatic encephalopathy, history of overt hepatic encephalopathy, C-reactive protein (CRP) and model for end-stage liver disease (MELD), IL-6 levels above the median remained independently associated with the development of overt hepatic encephalopathy. The predictive performance of IL-6 regarding the development of overt hepatic encephalopathy during the next 180 days (AUROC, 0.931) was numerically higher than that of MELD (AUROC, 0.841) or CRP (AUROC, 0.835). In patients without prior overt hepatic encephalopathy, the predictive performance of IL-6 (AUROC, 0.966) was even significantly higher than that of MELD (AUROC 0.843) or CRP (AUROC 0.850). The ideal cut-off for IL-6 in this setting was 23.5 pg/mL with a sensitivity and specificity of 89.3% and 89.5% respectively. CONCLUSION:IL-6 serum levels are closely linked to the development of overt hepatic encephalopathy in patients with liver cirrhosis.
Authors: Maurice Michel; Cornelius Hess; Leonard Kaps; Wolfgang M Kremer; Max Hilscher; Peter R Galle; Markus Moehler; Jörn M Schattenberg; Marcus-Alexander Wörns; Christian Labenz; Michael Nagel Journal: Sci Rep Date: 2021-10-15 Impact factor: 4.379
Authors: Simon Johannes Gairing; Julian Anders; Leonard Kaps; Michael Nagel; Maurice Michel; Wolfgang Maximilian Kremer; Max Hilscher; Peter Robert Galle; Jörn M Schattenberg; Marcus-Alexander Wörns; Christian Labenz Journal: Hepatol Commun Date: 2022-01-14
Authors: Wolfgang M Kremer; Michael Nagel; Michael Reuter; Max Hilscher; Maurice Michel; Leonard Kaps; Joachim Labenz; Peter R Galle; Martin F Sprinzl; Marcus-Alexander Wörns; Christian Labenz Journal: Clin Transl Gastroenterol Date: 2020-07 Impact factor: 4.396