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1. Editorial:non-invasive diagnosis of alcohol-related steatohepatitis in patients ongoing alcohol withdrawal based on cytokeratin 18 and transient elastography

Author: Thomsen, Karen L. and Gronbaek, Henning
Published: 2023

2. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF

Author: Moreau, Richard, Clària, Joan, Aguilar, Ferran, Fenaille, François, Lozano, Juanjo, Junot, Christophe, Colsch, Benoit, Caraceni, Paolo, Trebicka, Jonel, Pavesi, Marco, Alessandria, Carlo, Nevens, Frederik, Saliba, Faouzi, Welzel, Tania M., Albillos, Agustin, Gustot, Thierry, Fernández, Javier, Moreno, Christophe, Baldasarre, Maurizio, Zaccherini, Giacomo, Piano, Salvatore, Montagnese, Sara, Vargas, Victor, Genescà, Joan, Solà, Elsa, Bernal, William, Butin, Noémie, Hautbergue, Thaïs, Cholet, Sophie, Castelli, Florence, Jansen, Christian, Steib, Christian, Campion, Daniela, Mookerjee, Raj, Rodríguez-Gandía, Miguel, Soriano, German, Durand, François, Benten, Daniel, Bañares, Rafael, Stauber, Rudolf E., Gronbaek, Henning, Coenraad, Minneke J., Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Bernardi, Mauro, Arroyo, Vicente, Angeli, Paolo, BALDASSARRE, MAURIZIO, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Moreau, Richard, Clària, Joan, Aguilar, Ferran, Fenaille, Françoi, Lozano, Juanjo, Junot, Christophe, Colsch, Benoit, Caraceni, Paolo, Trebicka, Jonel, Pavesi, Marco, Alessandria, Carlo, Nevens, Frederik, Saliba, Faouzi, Welzel, Tania M., Albillos, Agustin, Gustot, Thierry, Fernández, Javier, Moreno, Christophe, Baldasarre, Maurizio, Zaccherini, Giacomo, Piano, Salvatore, Montagnese, Sara, Vargas, Victor, Genescà, Joan, Solà, Elsa, Bernal, William, Butin, Noémie, Hautbergue, Thaï, Cholet, Sophie, Castelli, Florence, Jansen, Christian, Steib, Christian, Campion, Daniela, Mookerjee, Raj, Rodríguez-Gandía, Miguel, Soriano, German, Durand, Françoi, Benten, Daniel, Bañares, Rafael, Stauber, Rudolf E., Gronbaek, Henning, Coenraad, Minneke J., Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Bernardi, Mauro, Arroyo, Vicente, and Angeli, Paolo
Subjects: 0301 basic medicine, Cirrhosis, Inflammation, Systemic inflammation, 03 medical and health sciences, 0302 clinical medicine, medicine, Metabolome, Decompensation, Biomarkers, CANONIC study, Multiorgan failure, Small-molecules, Kidney, Hepatology, Catabolism, business.industry, Lipidomic, Organ dysfunction, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Biomarker, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Multiorgan failure, Small-molecules, Immunology, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: Background & Aims: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze the blood metabolome in patients with cirrhosis, with and without ACLF. Methods: We performed untargeted metabolomics using liquid chromatography coupled to high-resolution mass spectrometry in serum from 650 patients with AD (acute decompensation of cirrhosis, without ACLF), 181 with ACLF, 43 with compensated cirrhosis, and 29 healthy individuals. Results: Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF of any grade, relative to those with AD, and 38 comprised a distinctive blood metabolite fingerprint for ACLF. Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism. The higher the ACLF-associated fingerprint intensity, the higher the plasma levels of inflammatory markers, tumor necrosis factor alpha, soluble CD206, and soluble CD163. ACLF was characterizedbyintense proteolysis andlipolysis; aminoacid catabolism; extra-mitochondrial glucose metabolism through glycolysis, pentose phosphate, and D-glucuronate pathways; depressed mitochondrial ATP-producing fatty acid beta-oxidation; and extramitochondrial amino acid metabolism giving rise to metabotoxins. Conclusions: In ACLF, intense systemic inflammation is associated with blood metabolite accumulation and profound alterations in major metabolic pathways, in particular inhibition of mitochondrial energy production, which may contribute to the development of organ failures. Lay summary: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. We identified a 38-metabolite blood fingerprint specific for ACLF that revealed mitochondrial dysfunction in peripheral organs. This may contribute to organ failures. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Published: 2020

3. Plasma protein biomarkers for the detection of pancreatic neuroendocrine tumors and differentiation from small intestinal neuroendocrine tumors

Author: Nordic NET Biomarker Grp, Thiis-Evensen, Espen, Kjellman, Magnus, Knigge, Ulrich, Gronbaek, Henning, Schalin-Jäntti, Camilla, Welin, Staffan, Sorbye, Halfdan, Schneider, Maria del Pilar, Belusa, Roger, HUS Abdominal Center, Clinicum, University of Helsinki, and Endokrinologian yksikkö
Subjects: diagnosis, Endocrinology, Diabetes and Metabolism, CHROMOGRANIN-A, POLYPEPTIDE, 3124 Neurology and psychiatry, Cellular and Molecular Neuroscience, Endocrinology, Intestinal Neoplasms, MANAGEMENT, Humans, Aged, Endocrine and Autonomic Systems, 3112 Neurosciences, Plasma proteins, CLINICAL UTILITY, Blood Proteins, CANCER, Pancreatic Neoplasms, NET, Neuroendocrine Tumors, machine learning, 3121 General medicine, internal medicine and other clinical medicine, biomarker, Female, Biomarkers, NEOPLASMS
Abstract: There is an unmet need for novel biomarkers to diagnose and monitor patients with neuroendocrine neoplasms. The EXPLAIN study explores a multi-plasma protein and supervised machine learning strategy to improve the diagnosis of pancreatic neuroendocrine tumors (PanNET) and differentiate them from small intestinal neuroendocrine tumors (SI-NET). At time of diagnosis, blood samples were collected and analyzed from 39 patients with PanNET, 135 with SI-NET (World Health Organization Grade 1–2) and 144 controls. Exclusion criteria were other malignant diseases, chronic inflammatory diseases, reduced kidney or liver function. Prosed Oncology-II (i.e., OLink) was used to measure 92 cancer related plasma proteins. Chromogranin A was analyzed separately. Median age in all groups was 65–67 years and with a similar sex distribution (females: PanNET, 51%; SI-NET, 42%; controls, 42%). Tumor grade (G1/G2): PanNET, 39/61%; SI-NET, 46/54%. Patients with liver metastases: PanNET, 78%; SI-NET, 63%. The classification model of PanNET versus controls provided a sensitivity (SEN) of 0.84, specificity (SPE) 0.98, positive predictive value (PPV) of 0.92 and negative predictive value (NPV) of 0.95, and area under the receiver operating characteristic curve (AUROC) of 0.99; the model for the discrimination of PanNET versus SI-NET providing a SEN 0.61, SPE 0.96, PPV 0.83, NPV 0.90 and AUROC 0.98. These results suggest that a multi-plasma protein strategy can significantly improve diagnostic accuracy of PanNET and SI-NET. publishedVersion
Published: 2022

4. Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode

Author: Villagrasa, Ares, Hernández-Gea, Virginia, Bataller, Ramon, Giráldez, Álvaro, Procopet, Bogdan, Amitrano, Lucio, Villanueva, Candid, Thabut, Dominique, Ibañez-Samaniego, Luis, Albillos, Agustin, Bureau, Christophe, Trebicka, Jonel, Llop, Elba, Laleman, Wim, Palazon, J M, Castellote, Jose, Rodrigues, Susana, Gluud, Lise L, Ferreira, Carlos N, Cañete, Nuria, Rodríguez, Manuel, Ferlitsch, Arnulf, Mundi, Jose L, Gronbaek, Henning, Hernández-Guerra, Manuel, Sassatelli, Romano, Dell'Era, Alessandra, Senzolo, Marco, Abraldes, Juan G, Zipprich, Alexander, Casas, Meritxell, Masnou, Helena, Primignani, Massimo, Krag, Aleksander, Silva-Junior, Gilberto, Romero-Gómez, Manuel, Tantau, Marcel, Guardascione, Maria A, Alvarado, Edilmar, Rudler, Marika, Bañares, Rafael, Martinez, Javier, Robic, Marie A, Jansen, Christian, Calleja, Jose L, Nevens, Frederik, Bosch, Jaime, Ventura-Cots, Meritxell, García-Pagan, Juan C, and Genescà, Joan
Subjects: alcohol, upper gastrointestinal bleeding, cirrhosis, alcohol-related hepatitis, 610 Medicine & health, abstinence
Abstract: BACKGROUND & AIMS Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.
Published: 2021

5. OPTIMAL TIMING OF ENDOSCOPY IS ASSOCIATED WITH LOWER 42-DAY MORTALITY IN VARICEAL BLEEDING

Author: Laursen, Stig B., Stanley, Adrian J., Hernandez-Gea, Virginia, Procopet, Bogdan, Giraldez, Alvaro, Sanchez, Candido V., Thabut, Dominique, Ibanez-Samaniego, Luis, Martinez, Javier, Genesca, Joan, Bureau, Christophe, Trebicka, Jonel, Llop, Elba, Laleman, Wim, Palazon, Jose M., Castellote, Jose, Rodrigues, Susana, Gluud, Lise L., Ferreira, Carlos Noronha, Barcelo, Rafael, Canete, Nuria, Rodriguez, Manuel, Ferlitsch, Arnulf, Mundi, Jose L., Gronbaek, Henning, Hernandez-Guerra, Manuel, Sassatelli, Romano, Dellera, Alessandra, Senzolo, Marco, Abraldes, Juan, Romero-Gomez, Manuel, Zipprich, Alexander, Casas, Meritxell, Masnou, Helena, Primignani, Massimo, Nevens, Frederik, Jansen, Christian, Robic, Marie A., Conejo, Irene, Catalina, Maria-Vega, Albillos, Agustin, Rudler, Marika, Alvarado, Edilmar A., Guardascione, Maria A., Tantau, Marcel, Bosch, Jaime, Torres, Ferran, Garcia-Pagan, Juan C., and Krag, Aleksander
Published: 2019

6. Monitoring Kidney Function in Neuroendocrine Tumor Patients Treated with 90Y-DOTATOC:Associations with Risk Factors

Author: Arveschoug, Anne K, Kramer, Stine M J, Iversen, Peter, Frøkiær, Jørgen, and Gronbaek, Henning
Subjects: urogenital system
Abstract: Peptide receptor radionuclide therapy (PRRT) is an established treatment for progressive neuroendocrine tumours with nephrotoxicity as the limiting factor. It is therefore important to monitor kidney function changes after PRRT treatment. We aimed to investigate kidney function by different methods and during a 4-hour and a 24-hour amino acid (AA) infusion protocol. We measured the Glomerular Filtration Rate (GFR) in 28 patients before and 3, 6, 12, and 18 months after 90Y-DOTATOC therapy. We used standardized 51Cr-EDTA plasma clearance (Cr-GFR) and estimated GFR (eGFR) by the simplified 4 variable Modification of Diet in Renal Disease based on serum creatinine values. Further, we determined GFR in 15 patients treated with a 4-hour infusion of AA compared to 13 patients with a 24-hour infusion at 3, 6, 12 and 18 months after therapy. Pre-existing risk factors associated with kidney failure were seen in 82% of the patients. We observed a significant reduction in Cr-GFR up to 12 months after PRRT (mean loss 27 ml/min/1,73 m2 (32%)). The eGFR continuously overestimated the Cr-GFR with a bias of 8%. There was no significant difference between the two AA protocols, however, the 24-hour AA protocol tended to reduce mean Cr-GFR loss 12 months post therapy. Pre-existing risk factors for kidney failure were highly prevalent in this patient cohort, and kidney function after PRRT treatment is best monitored by 51Cr-EDTA plasma clearance. Further, the use of a 24-hour AA kidney protection protocol seems to reduce the loss of kidney function in these patients.
Published: 2015

7. Insulin-like Growth Factor-I Concentration and Risk of Prostate Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

Author: Price, Alison J. Allen, Naomi E. Appleby, Paul N. Crowe, Francesca L. Travis, Ruth C. Tipper, Sarah J. Overvad, Kim and Gronbaek, Henning Tjonneland, Anne Johnsen, Nina Fons and Rinaldi, Sabina Kaaks, Rudolf Lukanova, Annie Boeing, Heiner and Aleksandrova, Krasimira Trichopoulou, Antonia Trichopoulos, Dimitrios Andarakis, George Palli, Domenico Krogh, Vittorio and Tumino, Rosario Sacerdote, Carlotta Bueno-de-Mesquita, H. Bas Argueelles, Marcial V. Sanchez, Maria-Jose Chirlaque, Maria-Dolores Barricarte, Aurelio Larranaga, Nerea Gonzalez, Carlos A. Stattin, Par Johansson, Mattias Khaw, Kay-Tee and Wareham, Nick Gunter, Marc Riboli, Elio Key, Timothy
Abstract: Background: High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups. Results: Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P-trend = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed 7 years after blood collection, respectively (P-heterogeneity = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P-heterogeneity >0.05). Conclusion: In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term. Impact: As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted. Cancer Epidemiol Biomarkers Prev; 21(9); 1531-41. (C) 2012 AACR.
Published: 2012

8. Goblet Cell Carcinoid in a Patient with Neurofibromatosis Type 1: A Rare Combination

Author: Gregersen, Tine, Holt, Nanna, Gronbaek, Henning, Vogel, Ida, Jørgensen, Lars J., and Krogh, Klaus
Subjects: Article Subject, respiratory system, digestive system, neoplasms, digestive system diseases
Abstract: Neuroendocrine tumors are rare tumors primarily located in the gastrointestinal tract. Goblet cell carcinoid is a rare subgroup of neuroendocrine tumors located in the appendix. Neurofibromatosis type 1 is an autosomal dominant disorder caused by a mutation in the NF1 gene. Patients with neurofibromatosis type 1 have an increased incidence of typical neuroendocrine tumors, but it is unknown if this is the case with goblet cell carcinoids. We describe a patient with both neurofibromatosis type 1 and goblet cell carcinoid, that according to literature would occur in 0.00017 per million per year. This may suggest a previously unknown association between neurofibromatosis type 1 and goblet cell carcinoids.
Published: 2012
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9. A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1-2 and-3 in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Crowe, Francesca L. Key, Timothy J. Allen, Naomi E. Appleby, Paul N. Overvad, Kim Gronbaek, Henning Tjonneland, Anne and Halkjaer, Jytte Dossus, Laure Boeing, Heiner Kroeger, Janine and Trichopoulou, Antonia Zylis, Dimosthenis Trichopoulos, Dimitrios Boutron-Ruault, Marie-Christine de Lauzon-Guillain, Blandine Clavel-Chapelon, Francoise Palli, Domenico Berrino, Franco Panico, Salvatore Tumino, Rosario Sacerdote, Carlotta and Bueno-de-Mesquita, H. Bas van Gils, Carla H. Peeters, Petra H. M. Gram, Inger T. Rodriguez, Laudina Jakszyn, Paula and Molina-Montes, Esther Navarro, Carmen Barricarte, Aurelio and Larranaga, Nerea Khaw, Kay-Tee Rodwell, Sheila Rinaldi, Sabina Slimani, Nadia Norat, Teresa Gallo, Valentina and Riboli, Elio Kaaks, Rudolf
Abstract: Background: Height and BMI are risk factors for several types of cancer and may be related to circulating concentrations of insulin-like growth factor-I (IGF-I), a peptide associated with increased cancer risk. Aim: To assess the associations between height, BMI and serum concentrations of IGF-I and IGF binding protein (IGFBP)-1, -2 and -3. Subjects and methods: This cross-sectional analysis included 1142 men and 3589 women aged 32-77 years from the multi-centre study, the European Prospective Investigation of Cancer and Nutrition (EPIC). Results: In men, there was a positive association between height and IGF-I; each 10 cm increment in height was associated with an increase in IGF-I concentrations of 4.3% (95% confidence interval (CI): 1.3-7.5%, p for trend = 0.005), but this association was not statistically significant for women (0.9%, 95% CI: -0.7 to 2.6%, p for trend = 0.264). In both men and women, the association between IGF-I and BMI was non-linear and those with a BMI of 26-27 kg/m(2) had the highest IGF-I concentration. BMI was strongly inversely related to concentrations of IGFBP-1 and IGFBP-2 in men and in women (p for trend for all < 0.001). Conclusion: Height and BMI are associated with IGF-I and its binding proteins, which may be mechanisms through which body size contributes to increased risk of several cancers.
Published: 2011

10. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies

Author: Rinaldi, Sabina Cleveland, Rebecca Norat, Teresa Biessy, Carine Rohrmann, Sabine Linseisen, Jakob Boeing, Heiner and Pischon, Tobias Panico, Salvatore Agnoli, Claudia Palli, Domenico Tumino, Rosario Vineis, Paolo Peeters, Petra H. M. and van Gils, Carla H. Bueno-de-Mesquita, Bas H. Vrieling, Alina and Allen, Naomi E. Roddam, Andrew Bingham, Sheila Khaw, Kay-Tee Manjer, Jonas Borgquist, Signe Dumeaux, Vanessa and Gram, Inger Torhild Lund, Eiliv Trichopoulou, Antonia and Makrygiannis, Georgios Benetou, Vassiliki Molina, Esther and Donate Suarez, Ignacio Barricarte Gurrea, Aurelio Gonzalez, Carlos A. Tormo, Maria-Jose Altzibar, Jone M. Olsen, Anja and Tjonneland, Anne Gronbaek, Henning Overvad, Kim and Clavel-Chapelon, Francoise Boutron-Ruault, Marie-Christine and Morois, Sophie Slimani, Nadia Boffetta, Paolo Jenab, Mazda and Riboli, Elio Kaaks, Rudolf
Abstract: Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I’s major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.
Published: 2010

11. The Association between Diet and Serum Concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition

Author: Crowe, Francesca L. Key, Timothy J. Allen, Naomi E. Appleby, Paul N. Roddam, Andrew Overvad, Kim Gronbaek, Henning and Tjonneland, Anne Halkjaer, Jutte Dossus, Laure Boeing, Heiner Kroeger, Janine Trichopoulou, Antonia Dilis, Vardis and Trichopoulos, Dimitrios Boutron-Ruault, Marie-Christine De Lauzon, Blandine Clavel-Chapelon, Francoise Palli, Domenico and Berrino, Franco Panico, Salvatore Tumino, Rosario Sacerdote, Carlotta Bueno-de-Mesquita, H. Bas Vrieling, Alina van Gils, Carla H. Peeters, Petra H. M. Gram, Inger T. Skeie, Guri and Lund, Eiliv Rodriguez, Laudina Jakszyn, Paula Molina-Montes, Esther Tormo, Maria J. Barricarte, Aurelio Larranaga, Nerea and Khaw, Kay-Tee Bingham, Sheila Rinaldi, Sabina Slimani, Nadia Norat, Teresa Gallo, Valentina Riboli, Elio Kaaks, Rudolf
Abstract: Circulating concentrations of insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) have been associated with the risk of several types of cancer. Dietary correlates of IGF-I and IGFBPs are not yet well established. The objective of this study was to assess the association between dietary intake and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in a cross-sectional analysis of 4,731 men and women taking part in the European Prospective Investigation into Cancer and Nutrition. Diet was assessed using country-specific validated dietary questionnaires. Serum concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 were measured, and the associations between diet and IGF-I and IGFBPs were assessed using multiple linear regression adjusting for sex, age, body mass index, smoking status, and alcohol and energy intake. Each I SD increment increase in total and dairy protein and calcium intake was associated with an increase in IGF-I concentration of 2.5%, 2.4%, and 3.3%, respectively (P for trend
Published: 2009

12. Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: Results from the European prospective investigation into cancer and nutrition

Author: Allen, Naomi E. Key, Timothy J. Appleby, Paul N. Travis, Ruth C. Roddam, Andrew W. Rinaldi, Sabina Egevad, Lars and Rohrmann, Sabine Linseisen, Jakob Pischon, Tobias Boeing, Heiner Johnsen, Nina Fons Tjonneland, Anne Gronbaek, Henning and Overvad, Kim Kiemeney, Lambartus Bueno-de-Mesquita, H. Bas and Bingham, Sheila Khaw, Kay Tee Tumino, Rosario Berrino, Franco Mattiello, Amalia Sacerdote, Carlotta Palli, Domenico and Quiros, Jos Ramon Ardanaz, Eva Navarro, Carmen and Larranaga, Nerea Gonzalez, Carlos Sanchez, Maria-Jose and Trichopoulou, Antonia Travezea, Cryssoula Trichopoulos, Dimitrios Jenab, Mazda Ferrari, Pietro Riboli, Elio and Kaaks, Rudolf
Abstract: Background: Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer. Methods: We analyzed the association between prediagnostic serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. This study includes 630 incident prostate cancer cases and 630 matched control subjects. Odds ratios and their 95% confidence intervals (95% CI) were calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3 concentrations using conditional logistic regression. Results: The risk of total prostate cancer in the highest versus the lowest third of serum peptide concentration was 1.35 (95% CI, 0.99-1.82; P-trend = 0.08) for IGF-I, 1.39 (95% CI, 1.02-1.89; P-trend = 0.12) for the IGF-I residuals after adjusting for IGFBP-3, 1.22 (95% CI, 0.92-1.64; P-trend = 0.38) for IGFBP-3, and 1.01 (95% CI, 0.74-1.37; P-trend = 0.75) for the IGFBP-3 residuals after adjusting for IGF-I. There was no significant difference in the association of peptide hormones and prostate cancer by stage of disease, although the association of serum IGF-l concentration with risk was slightly stronger for advanced-stage disease; the odds ratio for the highest versus the lowest third was 1.65 (95% CI, 0.88-3.08; P-trend = 0.21) for IGF-I and 1.76 (95% CI, 0.92-3.40; P-trend = 0.11) for IGF-I adjusted for IGFBP-3. Conclusions: In this large nested case-control study, serum IGF-I concentration is not strongly associated with prostate cancer risk, although the results are compatible with a small increase in risk, particularly for advanced-stage disease; no association for IGFBP-3 was observed.
Published: 2007

13. Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS

Author: Trebicka, Jonel, Gu, Wenyi, Ibáñez-Samaniego, Luis, Hernández-Gea, Virginia, Pitarch, Carla, Garcia, Elisabet, Procopet, Bogdan, Giráldez, Álvaro, Amitrano, Lucio, Villanueva, Candid, Thabut, Dominique, Silva-Junior, Gilberto, Martinez, Javier, Genescà, Joan, Bureau, Cristophe, Llop, Elba, Laleman, Wim, Palazon, Jose Maria, Castellote, Jose, Rodrigues, Susanag, Gluud, Liselotte, Ferreira, Carlos Noronha, Barcelo, Rafael, Cañete, Nuria, Rodríguez, Manuel, Ferlitsch, Arnulf, Mundi, Jose Luis, Gronbaek, Henning, Hernández-Guerra, Manuel, Sassatelli, Romano, Dell'Era, Alessandra, Senzolo, Marco, Abraldes, Juan G, Romero-Gómez, Manuel, Zipprich, Alexander, Casas, Meritxell, Masnou, Helena, Primignani, Massimo, Weiss, Emmanuel, Catalina, Maria-Vega, Erasmus, Hans-Peter, Uschner, Frank Erhard, Schulz, Martin, Brol, Maximilian J, Praktiknjo, Michael, Chang, Johannes, Krag, Aleksander, Nevens, Frederik, Calleja, Jose Luis, Robic, Marie Angèle, Conejo, Irene, Albillos, Agustin, Rudler, Marika, Alvarado, Edilmar, Guardascione, Maria Anna, Tantau, Marcel, Bosch, Jaime, Torres, Ferran, Pavesi, Marco, Garcia-Pagán, Juan Carlos, Jansen, Christian, and Bañares, Rafael
Subjects: 610 Medicine & health, 3. Good health
Abstract: BACKGROUND & AIMS The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p

14. Early-TIPS improves survival in high-risk variceal bleeders. Results of a Multicenter Variceal Bleeding Observational Study

Author: Hernandez-Gea, Virginia, Procopet, Bogdan, Giraldez, Alvaro, Amitrano, Lucio, Villanueva, Candid, Thabut, Dominique, Ibanez Samaniego, Luis, Silva-Junior, Gilberto, Albillos, Agustin, Genesca, Joan, Bureau, Christophe, Trebicka, Jonel, Llop, Elba, Laleman, Wim, Maria Palazon, Jose, Castellote, Jose, Rodrigues, Susana, Gluud, Lise L., Ferreira, Carlos Noronha, Canete, Nuria, Navascues, Carmen, Ferlitsch, Arnulf, Luis Mundi, Jose, Gronbaek, Henning, Hernandez-Guerra, Manuel, Sassatelli, Romano, Era, Alessandra, Senzolo, Marco, Abraldes, Juan G., Manuel Romero-Gómez, Zipprich, Alexander, Casas, Meritxell, Masnou, Helena, Primignani, Massimo, Torres, Ferran, Krag, Aleksander, Bosch, Jaime, and Carlos Garcia-Pagan, Juan

15. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Author: William Bernal, Agustín Albillos, Alex Amoros, Wim Laleman, Michael Manns, Javier Martínez, Maximilian J. Brol, Pere Ginès, Alessandra Pohlmann, Joerg Tobiasch Moritz, Francois Smits, Elisabet Garcia-Lopez, Joan Clària, Jennifer Lehmann, Jonel Trebicka, Christoph Welsch, Vicente Arroyo, Richard Moreau, Tony Bruns, Monica Mesquita, Christian Jansen, Peter Jarcuska, Harald Rupprechter, Martin Janicko, Thierry Gustot, Macarena Simón-Talero, Giacomo Zaccherini, Cristina Ripoll, Luise Aamann, Oliviero Riggio, Martina Rizzo, Karen Vagner Danielsen, Javier Romaní Fernández, Jelte J Schaapman, Frank Erhard Uschner, Juan Acevedo, Miguel Á. Rodríguez, David Semela, Carlo Alessandria, Carmine Gambino, Lise Lotte Gluud, Paolo Caraceni, Emanuela Ciraci, István Altorjay, Cristina Solé, Salvatore Piano, Minneke J. Coenraad, Pierre Nahon, Haluk Tarik Kani, Faouzi Saliba, Agnese Antognoli, Andrea De Gottardi, Osman Ozdogan, Henning Grønbæk, Christian J. Steib, Anna Curto, Hans Van Vlierberghe, Manuel Romero-Gómez, T.M. Welzel, Roland Amathieu, Sylvie Tresson, Carla Pitarch, Frederik Nevens, Alexander Zipprich, Christian Trautwein, Ilaria Giovo, Victor Vargas, Laure Elkrief, Giorgio Maria Saracco, Johannes Chang, Mattias Mandorfer, Paul Horn, Thomas Berg, Nesrine Amari, Sara Mareso, Heinz Zoller, Osagie Akpata, Mária Papp, Adam Herber, Thomas Reiberger, Flemming Bendtsen, Elsa Solà, Ferran Aguilar, Jose Presa Ramos, Miriam Maschmeier, Tamas Tornai, Manuela Merli, Rajiv Jalan, Martina Gagliardi, Cornelius Engelmann, Rafael Bañares, Daniela Campion, Antonella Putignano, Natalie Van den Ende, Claire Francoz, Marco Pavesi, Paola Ponzo, Rita Garcia, Sven Francque, Vish Patel, Esau Moreno, Alessandra Brocca, Rudolf E. Stauber, Zsuzsanna Vitális, Rajeshwar P. Mookerjee, Ahmed Elsharkawy, Eleonora Bertoli, Michael Praktiknjo, Stephen D. Ryder, Cristina Sanchez, Boglarka Balogh, Debbie L. Shawcross, Manuel Tufoni, Paolo Angeli, Florian Rainer, Pavel Strnad, István Tornai, Edilmar Alvarado-Tapias, Alexander L. Gerbes, Didier Samuel, Maurizio Baldassarre, Cesar Jimenez, Stefan Zeuzem, Pietro Gatti, Germán Soriano, Robert Schierwagen, Ana Clemente, Mauro Bernardi, Daniel Markwardt, Trebicka, Jonel, Fernandez, Javier, Papp, Maria, Caraceni, Paolo, Laleman, Wim, Gambino, Carmine, Giovo, Ilaria, Uschner, Frank Erhard, Jansen, Christian, Jimenez, Cesar, Mookerjee, Rajeshwar, Gustot, Thierry, Albillos, Agustin, Bañares, Rafael, Jarcuska, Peter, Steib, Christian, Reiberger, Thoma, Acevedo, Juan, Gatti, Pietro, Shawcross, Debbie L, Zeuzem, Stefan, Zipprich, Alexander, Piano, Salvatore, Berg, Thoma, Bruns, Tony, Danielsen, Karen Vagner, Coenraad, Minneke, Merli, Manuela, Stauber, Rudolf, Zoller, Heinz, Ramos, José Presa, Solé, Cristina, Soriano, Germán, de Gottardi, Andrea, Gronbaek, Henning, Saliba, Faouzi, Trautwein, Christian, Kani, Haluk Tarik, Francque, Sven, Ryder, Stephen, Nahon, Pierre, Romero-Gomez, Manuel, Van Vlierberghe, Han, Francoz, Claire, Manns, Michael, Garcia-Lopez, Elisabet, Tufoni, Manuel, Amoros, Alex, Pavesi, Marco, Sanchez, Cristina, Praktiknjo, Michael, Curto, Anna, Pitarch, Carla, Putignano, Antonella, Moreno, Esau, Bernal, William, Aguilar, Ferran, Clària, Joan, Ponzo, Paola, Vitalis, Zsuzsanna, Zaccherini, Giacomo, Balogh, Boglarka, Gerbes, Alexander, Vargas, Victor, Alessandria, Carlo, Bernardi, Mauro, Ginès, Pere, Moreau, Richard, Angeli, Paolo, Jalan, Rajiv, Arroyo, Vicente, Banares, Rafael, Reiberger, Thomas, Shawcross, Debbie L., Berg, Thomas, Ramos, Jose Presa, Sole, Cristina, Soriano, German, Van Vlierberghe, Hans, Claria, Joan, Gines, Pere, Maschmeier, Miriam, Semela, David, Elkrief, Laure, Elsharkawy, Ahmed, Tornai, Tamas, Tornai, Istvan, Altorjay, Istvan, Antognoli, Agnese, Baldassarre, Maurizio, Gagliardi, Martina, Bertoli, Eleonora, Mareso, Sara, Brocca, Alessandra, Campion, Daniela, Saracco, Giorgio Maria, Rizzo, Martina, Lehmann, Jennifer, Pohlmann, Alessandra, Brol, Maximilian J., Chang, Johannes, Schierwagen, Robert, Sola, Elsa, Amari, Nesrine, Rodriguez, Miguel, Nevens, Frederik, Clemente, Ana, Janicko, Martin, Markwardt, Daniel, Mandorfer, Mattias, Welsch, Christoph, Welzel, Tanja M., Ciraci, Emanuela, Patel, Vish, Ripoll, Cristina, Herber, Adam, Horn, Paul, Bendtsen, Flemming, Gluud, Lise Lotte, Schaapman, Jelte, Riggio, Oliviero, Rainer, Florian, Moritz, Joerg Tobiasch, Mesquita, Monica, Alvarado-Tapias, Edilmar, Akpata, Osagie, Aamann, Luise, Samuel, Didier, Tresson, Sylvie, Strnad, Pavel, Amathieu, Roland, Simon-Talero, Macarena, Smits, Francois, van den Ende, Natalie, Martinez, Javier, Garcia, Rita, Rupprechter, Harald, Engelmann, Cornelius, and Ozdogan, Osman Cavit
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Cirrhosis, Organ Dysfunction Scores, acute complication, Chronic liver disease, Acute complications, Non-elective admission, Outcome, Risk factors, 0302 clinical medicine, Preventive Health Services, Medicine and Health Sciences, Gastro-entérologie, risk factors, 610 Medicine & health, Medical History Taking, factors, Toxic encephalopathy, Bacterial Infections, Middle Aged, Prognosis, Europe, Cohort, Disease Progression, outcome, 030211 gastroenterology & hepatology, Female, medicine.symptom, Needs Assessment, Risk, medicine.medical_specialty, Alcoholic hepatitis, 03 medical and health sciences, Internal medicine, medicine, Humans, Decompensation, Medical history, Inflammation, Hepatology, business.industry, Hepatitis, Alcoholic, Organ dysfunction, Acute-On-Chronic Liver Failure, chronic liver disease, medicine.disease, Precipitating Factors, 030104 developmental biology, Human medicine, business, non-elective admission
Abstract: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF phenotype (AD-ACLF) defined by organ failure(s). Precipitants may induce AD. This multicenter, prospective, observational PREDICT study (NCT03056612) analyzes and characterizes the precipitants leading to both of these AD phenotypes., info:eu-repo/semantics/published
Published: 2021

16. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement

Author: Philip N. Newsome, Shira Zelber-Sagi, Elisabetta Bugianesi, Jian-Gao Fan, Manuel Romero-Gómez, Leon A. Adams, Jacob George, Luca Valenti, Takumi Kawaguchi, Gamal Shiha, Jörn M. Schattenberg, Yusuf Yilmaz, Shiv Kumar Sarin, Ming-Hua Zheng, Marco Arrese, Laurent Castera, Mohammed Eslam, Wah-Kheong Chan, Hannele Yki-Järvinen, Vlad Ratziu, Nahum Méndez-Sánchez, Jean-François Dufour, Quentin M. Anstee, Helena Cortez-Pinto, Yasser Fouad, Sang Hoon Ahn, Henning Grønbæk, Vincent Wai-Sun Wong, Giovanni Targher, Claudia P. Oliveira, Pierre Bedossa, Claudio Tiribelli, Eslam, Mohammed, Newsome, Philip N., Sarin, Shiv K., Anstee, Quentin M., Targher, Giovanni, Romero-Gomez, Manuel, Zelber-Sagi, Shira, Wong, Vincent Wai-Sun, Dufour, Jean-Francois, Schattenberg, Joern M., Kawaguchi, Takumi, Arrese, Marco, Valenti, Luca, Shiha, Gamal, Tiribelli, Claudio, Yki-Jarvinen, Hannele, Fan, Jian-Gao, Gronbaek, Henning, Yilmaz, Yusuf, Cortez-Pinto, Helena, Oliveira, Claudia P., Bedossa, Pierre, Adams, Leon A., Zheng, Ming-Hua, Fouad, Yasser, Chan, Wah-Kheong, Mendez-Sanchez, Nahum, Ahn, Sang Hoon, Castera, Laurent, Bugianesi, Elisabetta, Ratziu, Vlad, George, Jacob, Université de Paris (UP), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sydney Medical Foundation, University of Sydney, National Health and Medical Research Council (Australia), National Institute for Health Research (UK), Birmingham Biomedical Research Centre, University of Birmingham, and National Health Service (UK)
Subjects: Liver Cirrhosis, 0301 basic medicine, Cirrhosis, Diagnostic criteria, Diabetes, MAFLD, Metabolic, NAFLD, Obesity, Steatohepatitis, [SDV]Life Sciences [q-bio], HISTOLOGIC FEATURES, PROGRESSION, Disease, Terminology, 0302 clinical medicine, Medicine, 10. No inequality, NONALCOHOLIC STEATOHEPATITIS, Fatty liver, HIGH BLOOD-PRESSURE, HEALTHY OBESE, 3. Good health, PREVALENCE, Causality, Disease Progression, 030211 gastroenterology & hepatology, medicine.medical_specialty, Consensus, DIAGNOSIS, 03 medical and health sciences, Metabolic Diseases, Terminology as Topic, Diabetes mellitus, MANAGEMENT, Humans, Intensive care medicine, Hepatology, business.industry, Type 2 Diabetes Mellitus, NATURAL-HISTORY, medicine.disease, Fatty Liver, Clinical trial, 030104 developmental biology, Diabetes Mellitus, Type 2, business
Abstract: The exclusion of other chronic liver diseases including “excess” alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, “positive criteria” to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward., ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant ( APP1053206 , APP1149976 ) and Project grants ( APP1107178 and APP1108422 ). PNN is supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham .
Published: 2020

17. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Author: Sylvie Tresson, Sara Mareso, Daniela Campion, Agustín Albillos, Alex Amoros, Hans Van Vlierberghe, Manuel Romero-Gómez, Andrea De Gottardi, Thomas Reiberger, Vicente Arroyo, Boglarka Balogh, Miriam Maschmeier, Marco Pavesi, Javier Martínez, Harald Rupprechter, Sara Montagnese, Alessandra Pohlmann, Minneke J. Coenraad, Pierre Nahon, Agnese Antognoli, Jose Presa Ramos, Christoph Welsch, Alexander L. Gerbes, Pietro Gatti, Richard Moreau, Wim Laleman, Mauro Bernardi, Karen Vagner Danielsen, Laure Elkrief, Christian Jansen, Alexander Zipprich, Lise Lotte Gluud, Paul Horn, Ilaria Giovo, Roland Amathieu, Martina Rizzo, Elisabet Garcia, Joan Clària, Oliviero Riggio, Cristina Sanchez, Rita Garcia, Florian Rainer, Sven Francque, Manuela Merli, Giorgio Maria Saracco, Javier J.M. Fernández, Mária Papp, Martina Gagliardi, Antonella Putignano, Claire Francoz, Debbie L. Shawcross, Manuel Tufoni, Ferran Aguilar, Paola Ponzo, Heinz Zoller, Elsa Solà, Faouzi Saliba, Pavel Strnad, Stefan Zeuzem, Miguel Á. Rodríguez, David Semela, Peter Lykke Eriksen, Anna Curto, Rajiv Jalan, Emanuela Ciraci, Alessandra Brocca, István Altorjay, István Tornai, Edilmar Alvarado-Tapias, Jennifer Lehmann, Rajeshwar P. Mookerjee, Paolo Angeli, Rudolf E. Stauber, Ahmed Elsharkawy, Cristina Solé, Didier Samuel, Daniel Markwardt, Maurizio Baldassarre, Cornelius Engelmann, Cesar Jimenez, Pere Ginès, Frederik Nevens, Osagie Akpata, Germán Soriano, Robert Schierwagen, Eleonora Bertoli, Adam Herber, Jörg Tobiasch Moritz, Michael Praktiknjo, Natalie Van den Ende, William Bernal, Nesrine Amari, Stephen D. Ryder, Ana Clemente, Martin Janicko, Victor Vargas, Mattias Mandorfer, Flemming Bendtsen, Peter Jarcuska, Juan Acevedo, Vish Patel, Esau Moreno, Zsuzsanna Vitális, Tamas Tornai, Rafael Bañares, Christian J. Steib, Christian Trautwein, Thomas Berg, Michael Manns, Paolo Caraceni, Jelte J Schaapman, Carlo Alessandria, Carmine Gambino, Salvatore Piano, Carla Pitarch, Thierry Gustot, Osman Ozdogan, Francois Smits, Henning Grønbæk, Giacomo Zaccherini, Cristina Ripoll, Tony Bruns, Jonel Trebicka, Macarena Simón-Talero, Frank Erhard Uschner, Monica Mesquita, PREDICT STUDY Group, EASL-CLIF Consortium, Trebicka, Jonel, Fernandez, Javier, Papp, Maria, Caraceni, Paolo, Laleman, Wim, Gambino, Carmine, Giovo, Ilaria, Uschner, Frank Erhard, Jimenez, Cesar, Mookerjee, Rajeshwar, Gustot, Thierry, Albillos, Agustin, Banares, Rafael, Janicko, Martin, Steib, Christian, Reiberger, Thomas, Acevedo, Juan, Gatti, Pietro, Bernal, William, Zeuzem, Stefan, Zipprich, Alexander, Piano, Salvatore, Berg, Thomas, Bruns, Tony, Bendtsen, Flemming, Coenraad, Minneke, Merli, Manuela, Stauber, Rudolf, Zoller, Heinz, Ramos, Jose Presa, Sole, Cristina, Soriano, German, de Gottardi, Andrea, Gronbaek, Henning, Saliba, Faouzi, Trautwein, Christian, Ozdogan, Osman Cavit, Francque, Sven, Ryder, Stephen, Nahon, Pierre, Romero-Gomez, Manuel, Van Vlierberghe, Hans, Francoz, Claire, Manns, Michael, Garcia, Elisabet, Tufoni, Manuel, Amoros, Alex, Pavesi, Marco, Sanchez, Cristina, Curto, Anna, Pitarch, Carla, Putignano, Antonella, Moreno, Esau, Shawcross, Debbie, Aguilar, Ferran, Claria, Joan, Ponzo, Paola, Jansen, Christian, Vitalis, Zsuzsanna, Zaccherini, Giacomo, Balogh, Boglarka, Vargas, Victor, Montagnese, Sara, Alessandria, Carlo, Bernardi, Mauro, Gines, Pere, Jalan, Rajiv, Moreau, Richard, Angeli, Paolo, Arroyo, Vicente, Trebicka J., Fernandez J., Papp M., Caraceni P., Laleman W., Gambino C., Giovo I., Uschner F.E., Jimenez C., Mookerjee R., Gustot T., Albillos A., Banares R., Janicko M., Steib C., Reiberger T., Acevedo J., Gatti P., Bernal W., Zeuzem S., Zipprich A., Piano S., Berg T., Bruns T., Bendtsen F., Coenraad M., Merli M., Stauber R., Zoller H., Ramos J.P., Sole C., Soriano G., de Gottardi A., Gronbaek H., Saliba F., Trautwein C., Ozdogan O.C., Francque S., Ryder S., Nahon P., Romero-Gomez M., Van Vlierberghe H., Francoz C., Manns M., Garcia E., Tufoni M., Amoros A., Pavesi M., Sanchez C., Curto A., Pitarch C., Putignano A., Moreno E., Shawcross D., Aguilar F., Claria J., Ponzo P., Jansen C., Vitalis Z., Zaccherini G., Balogh B., Vargas V., Montagnese S., Alessandria C., Bernardi M., Gines P., Jalan R., Moreau R., Angeli P., Arroyo V., Maschmeier M., Semela D., Elkrief L., Elsharkawy A., Tornai T., Tornai I., Altorjay I., Antognoli A., Baldassarre M., Gagliardi M., Bertoli E., Mareso S., Brocca A., Campion D., Saracco G.M., Rizzo M., Lehmann J., Pohlmann A., Praktiknjo M., Schierwagen R., Sola E., Amari N., Rodriguez M., Nevens F., Clemente A., Jarcuska P., Gerbes A., Mandorfer M., Welsch C., Ciraci E., Patel V., Ripoll C., Herber A., Horn P., Danielsen K.V., Gluud L.L., Schaapman J., Riggio O., Rainer F., Moritz J.T., Mesquita M., Alvarado-Tapias E., Akpata O., Lykke Eriksen P., Samuel D., Tresson S., Strnad P., Amathieu R., Simon-Talero M., Smits F., van den Ende N., Martinez J., Garcia R., Markwardt D., Rupprechter H., and Engelmann C.
Subjects: Liver Cirrhosis, Male, CHRONIC LIVER-FAILURE, Cirrhosis, medicine.medical_treatment, Trasplantament hepàtic, Liver transplantation, Chronic liver disease, Severity of Illness Index, Acute complications, Non-elective admission, Outcome, Risk factors, acute complications, Ascites, Medicine and Health Sciences, Prospective Studies, 610 Medicine & health, Hepatic encephalopathy, Mortality rate, Sciences bio-médicales et agricoles, Middle Aged, Prognosis, Europe, Survival Rate, Hepatic cirrhosis, Portal hypertension, Female, medicine.symptom, medicine.medical_specialty, Cirrosi hepàtica, Gastrointestinal hemorrhage, INFLAMMATION, Internal medicine, Hypertension, Portal, SCORE, medicine, Humans, Decompensation, Hepatology, business.industry, MORTALITY, Acute-On-Chronic Liver Failure, Acute complication, Hemorràgia gastrointestinal, medicine.disease, Human medicine, Hepatic transplantation, business, Follow-Up Studies
Abstract: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF., info:eu-repo/semantics/published
Published: 2020

18. Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis

Author: Claria, J., Moreau, R., Fenaille, F., Amoros, A., Junot, C., Gronbaek, H., Coenraad, M.J., Pruvost, A., Ghettas, A., Chu-Van, E., Lopez-Vicario, C., Oettl, K., Caraceni, P., Alessandria, C., Trebicka, J., Pavesi, M., Deulofeu, C., Albillos, A., Gustot, T., Welzel, T.M., Fernandez, J., Stauber, R.E., Saliba, F., Butin, N., Colsch, B., Moreno, C., Durand, F., Nevens, F., Banares, R., Benten, D., Gines, P., Gerbes, A., Jalan, R., Angeli, P., Bernardi, M., Arroyo, V., EASL Clif Consortium, Grifols Chair European Fdn Study C, Clària, Joan, Moreau, Richard, Fenaille, Françoi, Amorós, Alex, Junot, Christophe, Gronbaek, Henning, Coenraad, Minneke J, Pruvost, Alain, Ghettas, Aurélie, Chu-Van, Emeline, López-Vicario, Cristina, Oettl, Karl, Caraceni, Paolo, Alessandria, Carlo, Trebicka, Jonel, Pavesi, Marco, Deulofeu, Carme, Albillos, Agustin, Gustot, Thierry, Welzel, Tania M, Fernández, Javier, Stauber, Rudolf E, Saliba, Faouzi, Butin, Noémie, Colsch, Benoit, Moreno, Christophe, Durand, Françoi, Nevens, Frederik, Bañares, Rafael, Benten, Daniel, Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Angeli, Paolo, Bernardi, Mauro, Arroyo, Vicente, Grifols Chair, Partenaires INRAE, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Université Paris Diderot - Paris 7 (UPD7), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Saclay (COmUE), Aarhus University Hospital, Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Institut National de la Recherche Agronomique (INRA), Medical University Graz, Department of Medical and Surgical Sciences, Universita degli Studi di Padova, San Giovanni Battista Hosp, Div Gastroenterol & Hepatol, Turin, Italy, Rheinische Friedrich-Wilhelms-Universität Bonn, Hospital Universitario, Université libre de Bruxelles (ULB), Goethe-Universität Frankfurt am Main, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université Catholique de Louvain = Catholic University of Louvain (UCL), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Univ Hosp LMU Munich, Liver Ctr Munich, Dept Med 2, Munich, Germany, University College of London [London] (UCL), Universita di Padova, ICREA Academia Award, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universiteit Leiden-Universiteit Leiden, and Università degli Studi di Padova = University of Padua (Unipd)
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Kynurenine pathway, [SDV]Life Sciences [q-bio], medicine.medical_treatment, severity, Decompensated cirrhosis, Systemic inflammation, Gastroenterology, Tryptophan -- blood, chemistry.chemical_compound, 0302 clinical medicine, hepatic-encephalopathy, Prospective Studies, Renal Insufficiency, Indoleamine 2,3-dioxygenase, Hepatic encephalopathy, Kynurenine, Liver Cirrhosis -- blood -- complications -- mortality -- physiopathology, systemic inflammation, Europe -- epidemiology, Kynurenine -- blood, Hepatic Encephalopathy -- blood -- complications, Tryptophan, Bacterial Infections -- blood -- complications, Immunosuppression, Bacterial Infections, Sciences bio-médicales et agricoles, Middle Aged, Acute-On-Chronic Liver Failure -- blood -- etiology, metabolomics, 3. Good health, Europe, chromatography, Female, 030211 gastroenterology & hepatology, medicine.symptom, metabolomic, medicine.medical_specialty, indoleamine 2,3-dioxygenase, Decompensated cirrhosi, 03 medical and health sciences, Internal medicine, medicine, Humans, organ failure, Decompensation, plasma, Aged, Inflammation, Inflammation -- blood -- complications, Renal Insufficiency -- blood -- complications, Hepatology, business.industry, Acute-On-Chronic Liver Failure, blockade, medicine.disease, mortality, kynurenine, 030104 developmental biology, chemistry, Case-Control Studies, Hepatic Encephalopathy, business, metabolism
Abstract: Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day follow-up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow-up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow-up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow-up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality., info:eu-repo/semantics/published
Published: 2019

19. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Author: Zobair M Younossi, Vlad Ratziu, Rohit Loomba, Mary Rinella, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Andreas Geier, Susanne Beckebaum, Philip N Newsome, David Sheridan, Muhammad Y Sheikh, James Trotter, Whitfield Knapple, Eric Lawitz, Manal F Abdelmalek, Kris V Kowdley, Aldo J Montano-Loza, Jerome Boursier, Philippe Mathurin, Elisabetta Bugianesi, Giuseppe Mazzella, Antonio Olveira, Helena Cortez-Pinto, Isabel Graupera, David Orr, Lise Lotte Gluud, Jean-Francois Dufour, David Shapiro, Jason Campagna, Luna Zaru, Leigh MacConell, Reshma Shringarpure, Stephen Harrison, Arun J Sanyal, Manal Abdelmalek, Gary Abrams, Humberto Aguilar, Aijaz Ahmed, Elmar Aigner, Guruprasad Aithal, Aftab Ala, William Alazawi, Agustin Albillos, Michael Allison, Sfa Al-Shamma, Raul Andrade, Pietro Andreone, Mario Angelico, Victor Ankoma-Sey, Quentin Anstee, Rodolphe Anty, Victor Araya, Juan Ignacio Arenas Ruiz, Perttu Arkkila, Marty Arora, Tarik Asselah, Jennifer Au, Oyekoya Ayonrinde, Robert James Bailey, Maya Balakrishnan, Kiran Bambha, Meena Bansal, Sidney Barritt, John Bate, Jorge Beato, Jaideep Behari, Pablo Bellot, Ziv Ben Ari, Michael Bennett, Marina Berenguer, Benedetta Terziroli Beretta-Piccoli, Thomas Berg, Maurizio Bonacini, Lucia Bonet, Brian Borg, Marc Bourliere, William Bowman, David Bradley, Marija Brankovic, Marius Braun, Jean-Pierre Bronowicki, Savino Bruno, Cindy Cai, Amy Calderon, José Luis Calleja Panero, Elizabeth Carey, Michal Carmiel, Jose Antonio Carrión, Matthew Cave, Cristina Chagas, Tawfik Chami, Alan Chang, Allan Coates, Jeremy Cobbold, Charlote Costentin, Kathleen Corey, Lynsey Corless, Javier Crespo, Oscar Cruz Pereira, Victor de Ledinghen, Andrew deLemos, Moises Diago, Mamie Dong, Jean-François Dufour, Predrag Dugalic, Winston Dunn, Magby Elkhashab, Michael Epstein, Maria Desamparados Escudero-Garcia, Ohad Etzion, Larry Evans, Robert Falcone, Conrado Fernandez, Jose Ferreira, Scott Fink, Kevin Finnegan, Roberto Firpi-Morell, Annarosa Floreani, Thierry Fontanges, Ryan Ford, Ewan Forrest, Andrew Fowell, Anna Ludovica Fracanzani, Sven Francque, Bradley Freilich, Juan Frias, Michael Fuchs, Javier Fuentes, Michael Galambos, Juan Gallegos, Anja Geerts, Jacob George, Maged Ghali, Reem Ghalib, Pierre Gholam, Pere Gines, Norman Gitlin, Tobias Goeser, John Goff, Stuart Gordon, Frederic Gordon, Odile Goria, Shaun Greer, Alla Grigorian, Henning Gronbaek, Maeva Guillaume, Naresh Gunaratnam, Dina Halegoua-De Marzio, Bilal Hameed, Stephanie Hametner, James Hamilton, Marek Hartleb, Tarek Hassanein, Dieter Häussinger, Paul Hellstern, Robert Herring, Eva Heurich, Christophe Hezode, Holger Hinrichsen, Peter Holland Fischer, Yves Horsmans, Jonathan Huang, Hyder Hussaini, Antoine Jakiche, Lennox Jeffers, Blake Jones, Rosa Jorge, Francisco Jorquera, Shoba Joshi, Alisan Kahraman, Kelly Kaita, Nicholas Karyotakis, Zeid Kayali, Stergios Kechagias, Thomas Kepczyk, Mandana Khalili, Hicham Khallafi, Johannes Kluwe, Anita Kohli, Kevin Korenblat, Kris Kowdley, Aleksander Krag, Richard Krause, Andreas Kremer, Karen Krok, Miodrag Krstic, Marcelo Kugelmas, Sonal Kumar, Scott Kuwada, Damien Labarriere, Michelle Lai, Wim Laleman, Pietro Lampertico, Alice Lee, Vincent Leroy, Steven Lidofsky, Tina Huey Lim, Joseph Lim, Donald Lipkis, Ester Little, Amadeo Lonardo, Michelle Long, Velimir Anthony Christopher Luketic, Yoav Lurie, Guilherme Macedo, Joana Magalhaes, Mihály Makara, Benedict Maliakkal, Michael Manns, Pinelopi Manousou, Parvez Mantry, Giulio Marchesini, Carla Marinho, Paul Marotta, Hanns-Ulrich Marschall, Linda Martinez, Marlyn Mayo, Mark McCullen, William McLaughlin, Uta Merle, Raphael Merriman, Apurva Modi, Esther Molina, Aldo Montano-Loza, Carlos Monteverde, Amilcar Morales Cardona, Sulleman Moreea, Christophe Moreno, Filomena Morisco, Abdullah Mubarak, Beat Muellhaupt, Sandeep Mukherjee, Tobias Müller, Aleksandar Nagorni, Jahnavi Naik, Guy Neff, Moises Nevah, Philip Newsome, Eric Nguyen-Khac, Mazen Noureddin, Jude Oben, Hans Orlent, James Orr, Grisell Ortiz-Lasanta, Violaine Ozenne, Prashant Pandya, Angelo Paredes, James Park, Joykumar Patel, Keyur Patel, Sonali Paul, Heather Patton, Markus Peck-Radosavljevic, Salvatore Petta, Stephen Pianko, Anna Piekarska, Neville Pimstone, Joseph Pisegna, Paul Pockros, Stanislas Pol, Michael Porayko, John Poulos, David Pound, Joe Pouzar, Jose Presa Ramos, Nikolaos Pyrsopoulos, Nila Rafiq, Kate Muller, Alnoor Ramji, Ravi Ravinuthala, Chakradhar Reddy, Gautham Reddy K G, K. Rajender Reddy K R, Frederic Regenstein, Robert Reindollar, Justin Reynolds, Andres Riera, Jose Rivera Acosta, Geert Robaeys, Stuart Roberts, Federico Rodriguez-Perez, Sandor Romero, Manuel Romero-Gomez, Raymond Rubin, Mariagrazia Rumi, Simon Rushbrook, Christian Rust, Michael Ryan, Rifaat Safadi, Adnan Said, Kimmo Salminen, Didier Samuel, John Santoro, Arun Sanyal, Souvik Sarkar, Cynthia Schaeffer, Jörn Schattenberg, Ingolf Schiefke, Eugene Schiff, Wolfgang Schmidt, Jeffrey Schneider, Jeoffrey Schouten, Michael Schultz, Giada Sebastiani, David Semela, Thomas Sepe, Aasim Sheikh, Muhammad Sheikh, Kenneth Sherman, Oren Shibolet, Mitchell Shiffman, Asma Siddique, Cyril Sieberhagen, Samuel Sigal, Katarzyna Sikorska, Krzysztof Simon, Marie Sinclair, Richard Skoien, Joel Solis, Siddharth Sood, Bob Souder, James Spivey, Per Stal, Laura Stinton, Simone Strasser, Petar Svorcan, Gyongzi Szabo, Andrew Talal, Edward Tam, Brent Tetri, Paul Thuluvath, Hillel Tobias, Krzysztof Tomasiewicz, Dawn Torres, Albert Tran, Michael Trauner, Christian Trautwein, Emanuel Tsochatzis, Esther Unitt, Victor Vargas, Istvan Varkonyi, Ella Veitsman, Umberto Vespasiani Gentilucci, David Victor, John Vierling, Catherine Vincent, Aron Vincze, Manfred von der Ohe, Natasha Von Roenn, Raj Vuppalanchi, Michael Waters, Kymberly Watt, Julia Wattacheril, Martin Weltman, Amanda Wieland, Gregory Wiener, Alonzo Williams A, Jeffrey Williams J, Jason Wilson, Maria Yataco, Eric Yoshida, Ziad Younes, Liyun Yuan, Adam Zivony, Donald Zogg, Heinz Zoller, Fabien Zoulim, Eli Zuckerman, Massimo Zuin, Younossi Z.M., Ratziu V., Loomba R., Rinella M., Anstee Q.M., Goodman Z., Bedossa P., Geier A., Beckebaum S., Newsome P.N., Sheridan D., Sheikh M.Y., Trotter J., Knapple W., Lawitz E., Abdelmalek M.F., Kowdley K.V., Montano-Loza A.J., Boursier J., Mathurin P., Bugianesi E., Mazzella G., Olveira A., Cortez-Pinto H., Graupera I., Orr D., Gluud L.L., Dufour J.-F., Shapiro D., Campagna J., Zaru L., MacConell L., Shringarpure R., Harrison S., Sanyal A.J., Abdelmalek M., Abrams G., Aguilar H., Ahmed A., Aigner E., Aithal G., Ala A., Alazawi W., Albillos A., Allison M., Al-Shamma S., Andrade R., Andreone P., Angelico M., Ankoma-Sey V., Anstee Q., Anty R., Araya V., Arenas Ruiz J.I., Arkkila P., Arora M., Asselah T., Au J., Ayonrinde O., Bailey R.J., Balakrishnan M., Bambha K., Bansal M., Barritt S., Bate J., Beato J., Behari J., Bellot P., Ben Ari Z., Bennett M., Berenguer M., Beretta-Piccoli B.T., Berg T., Bonacini M., Bonet L., Borg B., Bourliere M., Bowman W., Bradley D., Brankovic M., Braun M., Bronowicki J.-P., Bruno S., Cai C., Calleja Panero J.L., Carey E., Carmiel M., Carrion J.A., Cave M., Chagas C., Chami T., Chang A., Coates A., Cobbold J., Corey K., Corless L., Crespo J., Cruz Pereira O., de Ledinghen V., deLemos A., Diago M., Dugalic P., Dunn W., Elkhashab M., Epstein M., Escudero-Garcia M.D., Etzion O., Evans L., Falcone R., Fernandez C., Ferreira J., Fink S., Finnegan K., Firpi-Morell R., Floreani A., Fontanges T., Ford R., Forrest E., Fowell A., Fracanzani A.L., Francque S., Freilich B., Frias J., Fuchs M., Fuentes J., Galambos M., Gallegos J., Geerts A., George J., Ghali M., Ghalib R., Gholam P., Gines P., Gitlin N., Goeser T., Goff J., Gordon S., Gordon F., Goria O., Greer S., Grigorian A., Gronbaek H., Guillaume M., Gunaratnam N., Halegoua-De Marzio D., Hameed B., Hametner S., Hamilton J., Hartleb M., Hassanein T., Haussinger D., Hellstern P., Herring R., Heurich E., Hezode C., Hinrichsen H., Holland Fischer P., Horsmans Y., Huang J., Jakiche A., Jeffers L., Jones B., Jorge R., Jorquera F., Kahraman A., Kaita K., Karyotakis N., Kayali Z., Kechagias S., Kepczyk T., Khalili M., Khallafi H., Kluwe J., Kohli A., Korenblat K., Kowdley K., Krag A., Krause R., Kremer A., Krok K., Krstic M., Kugelmas M., Kumar S., Labarriere D., Lai M., Lampertico P., Lee A., Leroy V., Lidofsky S., Lim T.H., Lim J., Lipkis D., Little E., Lonardo A., Long M., Lurie Y., Macedo G., Makara M., Maliakkal B., Manns M., Manousou P., Mantry P., Marchesini G., Marinho C., Marotta P., Marschall H.-U., Mayo M., McCullen M., McLaughlin W., Merriman R., Modi A., Molina E., Montano-Loza A., Monteverde C., Moreea S., Moreno C., Morisco F., Mubarak A., Muellhaupt B., Mukherjee S., Muller T., Nagorni A., Naik J., Neff G., Nevah M., Newsome P., Nguyen-Khac E., Noureddin M., Oben J., Orlent H., Orr J., Ortiz-Lasanta G., Ozenne V., Pandya P., Paredes A., Park J., Patel J., Patel K., Uta M., Patton H., Peck-Radosavljevic M., Petta S., Pianko S., Piekarska A., Pimstone N., Pockros P., Pol S., Porayko M., Poulos J., Pound D., Pouzar J., Presa Ramos J., Pyrsopoulos N., Rafiq N., Muller K., Ramji A., Ravinuthala R., Reddy C., Reddy K G G., Reddy K R K.R., Regenstein F., Reindollar R., Riera A., Rivera Acosta J., Robaeys G., Roberts S., Rodriguez-Perez F., Romero-Gomez M., Rubin R., Rumi M., Rushbrook S., Rust C., Ryan M., Safadi R., Said A., Salminen K., Samuel D., Santoro J., Sanyal A., Sarkar S., Schaeffer C., Schattenberg J., Schiefke I., Schiff E., Schmidt W., Schneider J., Schouten J., Schultz M., Sebastiani G., Semela D., Sepe T., Sheikh A., Sheikh M., Sherman K., Shibolet O., Shiffman M., Siddique A., Sieberhagen C., Sigal S., Sikorska K., Simon K., Sinclair M., Skoien R., Solis J., Sood S., Souder B., Spivey J., Stal P., Stinton L., Strasser S., Svorcan P., Szabo G., Talal A., Tam E., Tetri B., Thuluvath P., Tobias H., Tomasiewicz K., Torres D., Trauner M., Trautwein C., Tsochatzis E., Unitt E., Vargas V., Varkonyi I., Veitsman E., Vespasiani Gentilucci U., Victor D., Vierling J., Vincent C., Vincze A., von der Ohe M., Von Roenn N., Vuppalanchi R., Waters M., Watt K., Weltman M., Wieland A., Wiener G., Williams A A., Williams J J., Wilson J., Yataco M., Yoshida E., Younes Z., Yuan L., Zivony A., Zogg D., Zoller H., Zoulim F., Zuckerman E., Zuin M., Repositório da Universidade de Lisboa, Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., Sheridan, D., Sheikh, M. Y., Trotter, J., Knapple, W., Lawitz, E., Abdelmalek, M. F., Kowdley, K. V., Montano-Loza, A. J., Boursier, J., Mathurin, P., Bugianesi, E., Mazzella, G., Olveira, A., Cortez-Pinto, H., Graupera, I., Orr, D., Gluud, L. L., Dufour, J. -F., Shapiro, D., Campagna, J., Zaru, L., Macconell, L., Shringarpure, R., Harrison, S., Sanyal, A. J., Abdelmalek, M., Abrams, G., Aguilar, H., Ahmed, A., Aigner, E., Aithal, G., Ala, A., Alazawi, W., Albillos, A., Allison, M., Al-Shamma, S., Andrade, R., Andreone, P., Angelico, M., Ankoma-Sey, V., Anstee, Q., Anty, R., Araya, V., Arenas Ruiz, J. I., Arkkila, P., Arora, M., Asselah, T., Au, J., Ayonrinde, O., Bailey, R. J., Balakrishnan, M., Bambha, K., Bansal, M., Barritt, S., Bate, J., Beato, J., Behari, J., Bellot, P., Ben Ari, Z., Bennett, M., Berenguer, M., Beretta-Piccoli, B. T., Berg, T., Bonacini, M., Bonet, L., Borg, B., Bourliere, M., Bowman, W., Bradley, D., Brankovic, M., Braun, M., Bronowicki, J. -P., Bruno, S., Cai, C., Calleja Panero, J. L., Carey, E., Carmiel, M., Carrion, J. A., Cave, M., Chagas, C., Chami, T., Chang, A., Coates, A., Cobbold, J., Corey, K., Corless, L., Crespo, J., Cruz Pereira, O., de Ledinghen, V., Delemos, A., Diago, M., Dugalic, P., Dunn, W., Elkhashab, M., Epstein, M., Escudero-Garcia, M. D., Etzion, O., Evans, L., Falcone, R., Fernandez, C., Ferreira, J., Fink, S., Finnegan, K., Firpi-Morell, R., Floreani, A., Fontanges, T., Ford, R., Forrest, E., Fowell, A., Fracanzani, A. L., Francque, S., Freilich, B., Frias, J., Fuchs, M., Fuentes, J., Galambos, M., Gallegos, J., Geerts, A., George, J., Ghali, M., Ghalib, R., Gholam, P., Gines, P., Gitlin, N., Goeser, T., Goff, J., Gordon, S., Gordon, F., Goria, O., Greer, S., Grigorian, A., Gronbaek, H., Guillaume, M., Gunaratnam, N., Halegoua-De Marzio, D., Hameed, B., Hametner, S., Hamilton, J., Hartleb, M., Hassanein, T., Haussinger, D., Hellstern, P., Herring, R., Heurich, E., Hezode, C., Hinrichsen, H., Holland Fischer, P., Horsmans, Y., Huang, J., Jakiche, A., Jeffers, L., Jones, B., Jorge, R., Jorquera, F., Kahraman, A., Kaita, K., Karyotakis, N., Kayali, Z., Kechagias, S., Kepczyk, T., Khalili, M., Khallafi, H., Kluwe, J., Kohli, A., Korenblat, K., Kowdley, K., Krag, A., Krause, R., Kremer, A., Krok, K., Krstic, M., Kugelmas, M., Kumar, S., Labarriere, D., Lai, M., Lampertico, P., Lee, A., Leroy, V., Lidofsky, S., Lim, T. H., Lim, J., Lipkis, D., Little, E., Lonardo, A., Long, M., Lurie, Y., Macedo, G., Makara, M., Maliakkal, B., Manns, M., Manousou, P., Mantry, P., Marchesini, G., Marinho, C., Marotta, P., Marschall, H. -U., Mayo, M., Mccullen, M., Mclaughlin, W., Merriman, R., Modi, A., Molina, E., Montano-Loza, A., Monteverde, C., Moreea, S., Moreno, C., Morisco, F., Mubarak, A., Muellhaupt, B., Mukherjee, S., Muller, T., Nagorni, A., Naik, J., Neff, G., Nevah, M., Newsome, P., Nguyen-Khac, E., Noureddin, M., Oben, J., Orlent, H., Orr, J., Ortiz-Lasanta, G., Ozenne, V., Pandya, P., Paredes, A., Park, J., Patel, J., Patel, K., Uta, M., Patton, H., Peck-Radosavljevic, M., Petta, S., Pianko, S., Piekarska, A., Pimstone, N., Pockros, P., Pol, S., Porayko, M., Poulos, J., Pound, D., Pouzar, J., Presa Ramos, J., Pyrsopoulos, N., Rafiq, N., Muller, K., Ramji, A., Ravinuthala, R., Reddy, C., Reddy K G, G., Reddy K R, K. R., Regenstein, F., Reindollar, R., Riera, A., Rivera Acosta, J., Robaeys, G., Roberts, S., Rodriguez-Perez, F., Romero-Gomez, M., Rubin, R., Rumi, M., Rushbrook, S., Rust, C., Ryan, M., Safadi, R., Said, A., Salminen, K., Samuel, D., Santoro, J., Sanyal, A., Sarkar, S., Schaeffer, C., Schattenberg, J., Schiefke, I., Schiff, E., Schmidt, W., Schneider, J., Schouten, J., Schultz, M., Sebastiani, G., Semela, D., Sepe, T., Sheikh, A., Sheikh, M., Sherman, K., Shibolet, O., Shiffman, M., Siddique, A., Sieberhagen, C., Sigal, S., Sikorska, K., Simon, K., Sinclair, M., Skoien, R., Solis, J., Sood, S., Souder, B., Spivey, J., Stal, P., Stinton, L., Strasser, S., Svorcan, P., Szabo, G., Talal, A., Tam, E., Tetri, B., Thuluvath, P., Tobias, H., Tomasiewicz, K., Torres, D., Trauner, M., Trautwein, C., Tsochatzis, E., Unitt, E., Vargas, V., Varkonyi, I., Veitsman, E., Vespasiani Gentilucci, U., Victor, D., Vierling, J., Vincent, C., Vincze, A., von der Ohe, M., Von Roenn, N., Vuppalanchi, R., Waters, M., Watt, K., Weltman, M., Wieland, A., Wiener, G., Williams A, A., Williams J, J., Wilson, J., Yataco, M., Yoshida, E., Younes, Z., Yuan, L., Zivony, A., Zogg, D., Zoller, H., Zoulim, F., Zuckerman, E., Zuin, M., Younossi, Zobair M, Ratziu, Vlad, Loomba, Rohit, Rinella, Mary, Anstee, Quentin M, Goodman, Zachary, Bedossa, Pierre, Geier, Andrea, Beckebaum, Susanne, Newsome, Philip N, Sheridan, David, Sheikh, Muhammad Y, Trotter, Jame, Knapple, Whitfield, Lawitz, Eric, Abdelmalek, Manal F, Kowdley, Kris V, Montano-Loza, Aldo J, Boursier, Jerome, Mathurin, Philippe, Bugianesi, Elisabetta, Mazzella, Giuseppe, Olveira, Antonio, Cortez-Pinto, Helena, Graupera, Isabel, Orr, David, Gluud, Lise Lotte, Dufour, Jean-Francoi, Shapiro, David, Campagna, Jason, Zaru, Luna, MacConell, Leigh, Shringarpure, Reshma, Harrison, Stephen, Sanyal, Arun J, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Ahmed, Aijaz, Aigner, Elmar, Aithal, Guruprasad, Ala, Aftab, Alazawi, William, Albillos, Agustin, Allison, Michael, Al-Shamma, Sfa, Andrade, Raul, Andreone, Pietro, Angelico, Mario, Ankoma-Sey, Victor, Anstee, Quentin, Anty, Rodolphe, Araya, Victor, Arenas Ruiz, Juan Ignacio, Arkkila, Perttu, Arora, Marty, Asselah, Tarik, Au, Jennifer, Ayonrinde, Oyekoya, Bailey, Robert Jame, Balakrishnan, Maya, Bambha, Kiran, Bansal, Meena, Barritt, Sidney, Bate, John, Beato, Jorge, Behari, Jaideep, Bellot, Pablo, Ben Ari, Ziv, Bennett, Michael, Berenguer, Marina, Beretta-Piccoli, Benedetta Terziroli, Berg, Thoma, Bonacini, Maurizio, Bonet, Lucia, Borg, Brian, Bourliere, Marc, Bowman, William, Bradley, David, Brankovic, Marija, Braun, Mariu, Bronowicki, Jean-Pierre, Bruno, Savino, Cai, Cindy, Calleja Panero, José Lui, Carey, Elizabeth, Carmiel, Michal, Carrión, Jose Antonio, Cave, Matthew, Chagas, Cristina, Chami, Tawfik, Chang, Alan, Coates, Allan, Cobbold, Jeremy, Corey, Kathleen, Corless, Lynsey, Crespo, Javier, Cruz Pereira, Oscar, de Ledinghen, Victor, deLemos, Andrew, Diago, Moise, Dufour, Jean-Françoi, Dugalic, Predrag, Dunn, Winston, Elkhashab, Magby, Epstein, Michael, Escudero-Garcia, Maria Desamparado, Etzion, Ohad, Evans, Larry, Falcone, Robert, Fernandez, Conrado, Ferreira, Jose, Fink, Scott, Finnegan, Kevin, Firpi-Morell, Roberto, Floreani, Annarosa, Fontanges, Thierry, Ford, Ryan, Forrest, Ewan, Fowell, Andrew, Fracanzani, Anna Ludovica, Francque, Sven, Freilich, Bradley, Frias, Juan, Fuchs, Michael, Fuentes, Javier, Galambos, Michael, Gallegos, Juan, Geerts, Anja, George, Jacob, Ghali, Maged, Ghalib, Reem, Gholam, Pierre, Gines, Pere, Gitlin, Norman, Goeser, Tobia, Goff, John, Gordon, Stuart, Gordon, Frederic, Goria, Odile, Greer, Shaun, Grigorian, Alla, Gronbaek, Henning, Guillaume, Maeva, Gunaratnam, Naresh, Halegoua-De Marzio, Dina, Hameed, Bilal, Hametner, Stephanie, Hamilton, Jame, Hartleb, Marek, Hassanein, Tarek, Häussinger, Dieter, Hellstern, Paul, Herring, Robert, Heurich, Eva, Hezode, Christophe, Hinrichsen, Holger, Holland Fischer, Peter, Horsmans, Yve, Huang, Jonathan, Jakiche, Antoine, Jeffers, Lennox, Jones, Blake, Jorge, Rosa, Jorquera, Francisco, Kahraman, Alisan, Kaita, Kelly, Karyotakis, Nichola, Kayali, Zeid, Kechagias, Stergio, Kepczyk, Thoma, Khalili, Mandana, Khallafi, Hicham, Kluwe, Johanne, Kohli, Anita, Korenblat, Kevin, Kowdley, Kri, Krag, Aleksander, Krause, Richard, Kremer, Andrea, Krok, Karen, Krstic, Miodrag, Kugelmas, Marcelo, Kumar, Sonal, Labarriere, Damien, Lai, Michelle, Lampertico, Pietro, Lee, Alice, Leroy, Vincent, Lidofsky, Steven, Lim, Tina Huey, Lim, Joseph, Lipkis, Donald, Little, Ester, Lonardo, Amadeo, Long, Michelle, Lurie, Yoav, Macedo, Guilherme, Makara, Mihály, Maliakkal, Benedict, Manns, Michael, Manousou, Pinelopi, Mantry, Parvez, Marchesini, Giulio, Marinho, Carla, Marotta, Paul, Marschall, Hanns-Ulrich, Mayo, Marlyn, McCullen, Mark, McLaughlin, William, Merriman, Raphael, Modi, Apurva, Molina, Esther, Montano-Loza, Aldo, Monteverde, Carlo, Moreea, Sulleman, Moreno, Christophe, Morisco, Filomena, Mubarak, Abdullah, Muellhaupt, Beat, Mukherjee, Sandeep, Müller, Tobia, Nagorni, Aleksandar, Naik, Jahnavi, Neff, Guy, Nevah, Moise, Newsome, Philip, Nguyen-Khac, Eric, Noureddin, Mazen, Oben, Jude, Orlent, Han, Orr, Jame, Ortiz-Lasanta, Grisell, Ozenne, Violaine, Pandya, Prashant, Paredes, Angelo, Park, Jame, Patel, Joykumar, Patel, Keyur, Uta, Merle, Patton, Heather, Peck-Radosavljevic, Marku, Petta, Salvatore, Pianko, Stephen, Piekarska, Anna, Pimstone, Neville, Pockros, Paul, Pol, Stanisla, Porayko, Michael, Poulos, John, Pound, David, Pouzar, Joe, Presa Ramos, Jose, Pyrsopoulos, Nikolao, Rafiq, Nila, Muller, Kate, Ramji, Alnoor, Ravinuthala, Ravi, Reddy, Chakradhar, Reddy K G, Gautham, Reddy K R, K. Rajender, Regenstein, Frederic, Reindollar, Robert, Riera, Andre, Rivera Acosta, Jose, Robaeys, Geert, Roberts, Stuart, Rodriguez-Perez, Federico, Romero-Gomez, Manuel, Rubin, Raymond, Rumi, Mariagrazia, Rushbrook, Simon, Rust, Christian, Ryan, Michael, Safadi, Rifaat, Said, Adnan, Salminen, Kimmo, Samuel, Didier, Santoro, John, Sanyal, Arun, Sarkar, Souvik, Schaeffer, Cynthia, Schattenberg, Jörn, Schiefke, Ingolf, Schiff, Eugene, Schmidt, Wolfgang, Schneider, Jeffrey, Schouten, Jeoffrey, Schultz, Michael, Sebastiani, Giada, Semela, David, Sepe, Thoma, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shibolet, Oren, Shiffman, Mitchell, Siddique, Asma, Sieberhagen, Cyril, Sigal, Samuel, Sikorska, Katarzyna, Simon, Krzysztof, Sinclair, Marie, Skoien, Richard, Solis, Joel, Sood, Siddharth, Souder, Bob, Spivey, Jame, Stal, Per, Stinton, Laura, Strasser, Simone, Svorcan, Petar, Szabo, Gyongzi, Talal, Andrew, Tam, Edward, Tetri, Brent, Thuluvath, Paul, Tobias, Hillel, Tomasiewicz, Krzysztof, Torres, Dawn, Trauner, Michael, Trautwein, Christian, Tsochatzis, Emanuel, Unitt, Esther, Vargas, Victor, Varkonyi, Istvan, Veitsman, Ella, Vespasiani Gentilucci, Umberto, Victor, David, Vierling, John, Vincent, Catherine, Vincze, Aron, von der Ohe, Manfred, Von Roenn, Natasha, Vuppalanchi, Raj, Waters, Michael, Watt, Kymberly, Weltman, Martin, Wieland, Amanda, Wiener, Gregory, Williams A, Alonzo, Williams J, Jeffrey, Wilson, Jason, Yataco, Maria, Yoshida, Eric, Younes, Ziad, Yuan, Liyun, Zivony, Adam, Zogg, Donald, Zoller, Heinz, Zoulim, Fabien, Zuckerman, Eli, Zuin, Massimo, and REGENERATE Study Investigators
Subjects: Male, Biopsy, Clinical Trial, Phase III, Administration, Oral, 030204 cardiovascular system & hematology, Chronic liver disease, Settore MED/04, Biomarkers/analysis, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, Non-alcoholic Fatty Liver Disease, Clinical endpoint, Medicine, 030212 general & internal medicine, 610 Medicine & health, Chenodeoxycholic Acid/administration & dosage, education.field_of_study, Liver Function Test, Research Support, Non-U.S. Gov't, Fatty liver, Obeticholic acid, NASH, OBETICHOLIC ACID, General Medicine, Middle Aged, Multicenter Study, Randomized Controlled Trial, Administration, Female, Biomarkers, Chenodeoxycholic Acid, Double-Blind Method, Humans, Human, Oral, medicine.medical_specialty, Population, Placebo, 03 medical and health sciences, Research Support, N.I.H., Extramural, Internal medicine, Journal Article, education, Intention-to-treat analysis, business.industry, Biomarker, Interim analysis, medicine.disease, Non-alcoholic Fatty Liver Disease/drug therapy, chemistry, Human medicine, business
Abstract: © 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
Published: 2019
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20. Cell death markers in patients with cirrhosis and acute decompensation

Author: Alex Amoros, Richard Moreau, Elsa Solà, Alexander L. Gerbes, Fausto Andreola, Paolo Caraceni, Yu Bao Zheng, Patrik Bachtiger, Stewart Macdonald, Pere Ginès, Vicente Arroyo, Marco Pavesi, Rajiv Jalan, Rajeshwar P. Mookerjee, Henning Grønbæk, Macdonald, Stewart, Andreola, Fausto, Bachtiger, Patrik, Amoros, Alex, Pavesi, Marco, Mookerjee, Rajeshwar, Zheng, Yu Bao, Gronbaek, Henning, Gerbes, Alexander L., Sola, Elsa, Caraceni, Paolo, Moreau, Richard, Gines, Pere, Arroyo, Vicente, Jalan, Rajiv, and Universitat de Barcelona
Subjects: Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Systemic inflammation, Severity of Illness Index, Gastroenterology, Keratin 18, Liver cells, 0302 clinical medicine, Medicine, Prospective Studies, Cell Death, Malalties del fetge, Biochemical markers, Liver Cirrhosis/blood, Middle Aged, Pathophysiology, Liver, Hepatic cirrhosis, Marcadors bioquímics, Female, 030211 gastroenterology & hepatology, Liver/pathology, medicine.symptom, Adult, medicine.medical_specialty, Acute-On-Chronic Liver Failure/blood, Cirrosi hepàtica, Keratin-18/blood, Enzyme-Linked Immunosorbent Assay, macromolecular substances, Article, Cèl·lules hepàtiques, 03 medical and health sciences, Internal medicine, Severity of illness, Humans, Decompensation, Survival analysis, Liver diseases, Aged, Keratin-18, Hepatology, business.industry, Liver failure, Acute-On-Chronic Liver Failure, medicine.disease, Survival Analysis, 030104 developmental biology, Insuficiència hepàtica, business, Biomarkers/blood, Biomarkers
Abstract: The aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma-based biomarkers. The patients studied were part of the CANONIC (CLIF Acute-on-Chronic Liver Failure in Cirrhosis) study (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable patients with cirrhosis, and a group of 16 AD patients for histological studies. Caspase-cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in plasma by enzyme-linked immunosorbent assay. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine aminotransferase, and bilirubin, but not with markers of extrahepatic organ injury. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF-C AD score in prediction of progression from AD to ACLF (P < 0.05).CONCLUSION: Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Nonapoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury, and type of organ failure. (Hepatology 2018;67:989-1002).
Published: 2018

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20 results on '"Gronbaek, Henning"'

1. Editorial:non-invasive diagnosis of alcohol-related steatohepatitis in patients ongoing alcohol withdrawal based on cytokeratin 18 and transient elastography

2. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF

3. Plasma protein biomarkers for the detection of pancreatic neuroendocrine tumors and differentiation from small intestinal neuroendocrine tumors

4. Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode

5. OPTIMAL TIMING OF ENDOSCOPY IS ASSOCIATED WITH LOWER 42-DAY MORTALITY IN VARICEAL BLEEDING

6. Monitoring Kidney Function in Neuroendocrine Tumor Patients Treated with 90Y-DOTATOC:Associations with Risk Factors

7. Insulin-like Growth Factor-I Concentration and Risk of Prostate Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

8. Goblet Cell Carcinoid in a Patient with Neurofibromatosis Type 1: A Rare Combination

9. A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1-2 and-3 in the European Prospective Investigation into Cancer and Nutrition (EPIC)

10. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies

11. The Association between Diet and Serum Concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition

12. Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: Results from the European prospective investigation into cancer and nutrition

13. Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS

14. Early-TIPS improves survival in high-risk variceal bleeders. Results of a Multicenter Variceal Bleeding Observational Study

15. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

16. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement

17. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

18. Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis

19. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

20. Cell death markers in patients with cirrhosis and acute decompensation

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