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1. Multimodal decoding of human liver regeneration

Author

Matchett, K. P., Wilson-Kanamori, J. R., Portman, J. R., Kapourani, C. A., Fercoq, F., May, S., Zajdel, E., Beltran, M., Sutherland, E. F., Mackey, J. B. G., Brice, M., Wilson, G. C., Wallace, S. J., Kitto, L., Younger, N. T., Dobie, R., Mole, D. J., Oniscu, G. C., Wigmore, S. J., Ramachandran, P., Vallejos, C. A., Carragher, N. O., Saeidinejad, M. M., Quaglia, A., Jalan, R., Simpson, K. J., Kendall, T. J., Rule, J. A., Lee, W. M., Hoare, M., Weston, C. J., Marioni, J. C., Teichmann, S. A., Bird, T. G., Carlin, L. M., and Henderson, N. C.

Published
2024
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2. Intensive care management of acute-on-chronic liver failure

Author

Perricone, G, Artzner, T, De Martin, E, Jalan, R, Wendon, J, Carbone, M, Perricone G., Artzner T., De Martin E., Jalan R., Wendon J., Carbone M., Perricone, G, Artzner, T, De Martin, E, Jalan, R, Wendon, J, Carbone, M, Perricone G., Artzner T., De Martin E., Jalan R., Wendon J., and Carbone M.

Abstract

Acute-on-chronic liver failure (ACLF) is a clinical syndrome defined by an acute deterioration of the liver function associated with extrahepatic organ failures requiring intensive care support and associated with a high short-term mortality. ACLF has emerged as a major cause of mortality in patients with cirrhosis and chronic liver disease. ACLF has a unique pathophysiology in which systemic inflammation plays a key role; this provides the basis of novel therapies, several of which are now in clinical trials. Intensive care unit (ICU) therapy parallels that applied in the general ICU population in some organ failures but has peculiar differential characteristics in others. Critical care management strategies and the option of liver transplantation (LT) should be balanced with futility considerations in those with a poor prognosis. Nowadays, LT is the only life-saving treatment that can radically improve the long-term prognosis of patients with ACLF. This narrative review will provide insights on the current understanding of ACLF with emphasis on intensive care management.

Published
2023

3. Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis

Author

Ariza, X., Graupera, I., Coll, M., Solà, E., Barreto, R., García, E., Moreira, R., Elia, C., Morales-Ruiz, M., Llopis, M., Huelin, P., Solé, C., Fabrellas, N., Weiss, E., Nevens, F., Gerbes, A., Trebicka, J., Saliba, F., Fondevila, C., Hernández-Gea, V., Fernández, J., Bernardi, M., Arroyo, V., Jiménez, W., Deulofeu, C., Pavesi, M., Angeli, P., Jalan, R., Moreau, R., Sancho-Bru, P., and Ginès, P.

Published
2016
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4. Effect Of Parental Involvement In The Academic Performance Of The Children- A Survey

Author

Jalan, R. Shradha, Sinduja, Palati, Brundha, M. P., and Priyadharshini

Subjects
Innovative method, Behavior, Schools, Improvement, Academics, Learning, Parental involvement, Awareness, Education
Abstract

Introduction: Parental involvement includes several different forms of participation in education and with the schools. Parents can support their children's schooling by attending school functions and responding to school obligations .They can become more involved in helping their children improve their school work-providing encouragement, arranging for appropriate study time and space, modeling desired behavior, monitoring homework, and actively tutoring their children at home. Aim: The aim of this survey was to spread awareness about parental involvement in academics. Materials and methods: A questionnaire was distributed through an online google form link to about 100 people. The study population was asked to fill out the online form .Descriptive statistics were performed to evaluate the frequency and percentages of these variables. Age was stratified into various groups at many intervals. The other features such as sex, location, age and gender and their outcomes are analyzed. Chi square test was done using the SPSS software to find the relationship between the data such as age, sex, gender, and location. Results: The results were collected and the data was analyzed using SPSS version 20. From the study population, the whole of 100% of the participants gave a positive response when asked if they were aware of parental involvement in academics. Conclusion: The study evaluated the effect of parental involvement in academics. The majority of the study population is aware of parental involvement in academics.

Published
2023

15. Location and allocation: inequity of access to liver transplantation for patients with severe acute‐on‐chronic liver failure in Europe

Author

Artzner, T, Bernal, W, Belli, L, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinowich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Besch, C, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Fondevila, C, Duvoux, C, Jalan, R, Viganò, R, Mazzarelli, C, Lauterio, A, Giacomoni, A, Donato, F, Lampertico, P, Pasulo, L, Fagiuoli, S, Colledan, M, Cristina Morelli, M, Vitale, G, Ottobrelli, A, Patrono, D, Romagnoli, R, Petridis, I, Cillo, U, Germani, G, Burra, P, Bachellier, P, Schneider, F, Castelain, V, Addeo, P, Deridder, M, Caroline Sacleux Audrey Coilly, S, Faouzi, S, Samuel, D, Guichon, C, Faure, S, Ursic‐bedoya, J, Colmenero, J, Toapanta, D, Hernández‐tejero, M, Vinaixa, C, den Hoed, C, Haan, J, Della Penna, A, Erhard Uschner, F, Welker, M, Zeuzem, S, Bechstein, W, Goossens, N, Raszeja‐wyszomirska, J, Rabinovich, L, Katarey, D, Agarwal, B, Artzner, Thierry, Bernal, William, Belli, Luca S, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie‐Caroline, Pageaux, George‐Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinowich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Besch, Camille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Fondevila, Constantino, Duvoux, Christophe, Jalan, Rajiv, Viganò, Raffaella, Mazzarelli, Chiara, Lauterio, Andrea, Giacomoni, Alessandro, Donato, Francesca, Lampertico, Pietro, Pasulo, Luisa, Fagiuoli, Stefano, Colledan, Michele, Cristina Morelli, Maria, Vitale, Giovanni, Ottobrelli, Antonio, Patrono, Damiano, Romagnoli, Renato, Petridis, Ioannis, Cillo, Umberto, Germani, Giacomo, Burra, Patrizia, Bachellier, Philippe, Schneider, Francis, Castelain, Vincent, Addeo, Pietro, Deridder, Mathilde, Caroline Sacleux Audrey Coilly, Sophie, Faouzi, Saliba, Adam, Rene, Samuel, Didier, Guichon, Celine, Faure, Stéfanie, Ursic‐Bedoya, Josè, Fondevila, Costantino, Colmenero, Jorde, Toapanta, David, Hernández‐Tejero, María, Vinaixa, Carmen, Polak, Wojciech G., den Hoed, Caroline, Haan, Jubi E., Della Penna, Andrea, Erhard Uschner, Frank, Welker, Martin, Zeuzem, Stefan, Bechstein, Wolf, Goossens, Nicolas, Raszeja‐Wyszomirska, Joanna, Rabinovich, Liane, Katarey, Dev, Agarwal, Banwari, Artzner, T, Bernal, W, Belli, L, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinowich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Besch, C, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Fondevila, C, Duvoux, C, Jalan, R, Viganò, R, Mazzarelli, C, Lauterio, A, Giacomoni, A, Donato, F, Lampertico, P, Pasulo, L, Fagiuoli, S, Colledan, M, Cristina Morelli, M, Vitale, G, Ottobrelli, A, Patrono, D, Romagnoli, R, Petridis, I, Cillo, U, Germani, G, Burra, P, Bachellier, P, Schneider, F, Castelain, V, Addeo, P, Deridder, M, Caroline Sacleux Audrey Coilly, S, Faouzi, S, Samuel, D, Guichon, C, Faure, S, Ursic‐bedoya, J, Colmenero, J, Toapanta, D, Hernández‐tejero, M, Vinaixa, C, den Hoed, C, Haan, J, Della Penna, A, Erhard Uschner, F, Welker, M, Zeuzem, S, Bechstein, W, Goossens, N, Raszeja‐wyszomirska, J, Rabinovich, L, Katarey, D, Agarwal, B, Artzner, Thierry, Bernal, William, Belli, Luca S, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie‐Caroline, Pageaux, George‐Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, François, Rabinowich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Besch, Camille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Fondevila, Constantino, Duvoux, Christophe, Jalan, Rajiv, Viganò, Raffaella, Mazzarelli, Chiara, Lauterio, Andrea, Giacomoni, Alessandro, Donato, Francesca, Lampertico, Pietro, Pasulo, Luisa, Fagiuoli, Stefano, Colledan, Michele, Cristina Morelli, Maria, Vitale, Giovanni, Ottobrelli, Antonio, Patrono, Damiano, Romagnoli, Renato, Petridis, Ioannis, Cillo, Umberto, Germani, Giacomo, Burra, Patrizia, Bachellier, Philippe, Schneider, Francis, Castelain, Vincent, Addeo, Pietro, Deridder, Mathilde, Caroline Sacleux Audrey Coilly, Sophie, Faouzi, Saliba, Adam, Rene, Samuel, Didier, Guichon, Celine, Faure, Stéfanie, Ursic‐Bedoya, Josè, Fondevila, Costantino, Colmenero, Jorde, Toapanta, David, Hernández‐Tejero, María, Vinaixa, Carmen, Polak, Wojciech G., den Hoed, Caroline, Haan, Jubi E., Della Penna, Andrea, Erhard Uschner, Frank, Welker, Martin, Zeuzem, Stefan, Bechstein, Wolf, Goossens, Nicolas, Raszeja‐Wyszomirska, Joanna, Rabinovich, Liane, Katarey, Dev, and Agarwal, Banwari

Abstract

Background: There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies and LT activity for ACLF-3 patients across transplant centers in Europe. Methods: Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3 between 2018 and 2019 were included across 20 transplantation centers. Results: 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted ACLF-3 patients admitted to the ICU and the number listed or transplanted whilst in ACLF-3 across centers. In contrast, there was a correlation between the number of patients listed and the number transplanted whilst in ACLF-3. 21% of patients who were listed whilst in ACLF-3 died on the waiting list or were delisted. The percentage of LT for ACLF-3 patients varied from 0%-29% of patients transplanted with decompensated cirrhosis across centers (average = 8%), with an I2 index of 68% (95% CI: 49%-80%), showing substantial heterogeneity among centers. The one-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more ACLF-3 patients (>10 patients) than in centers that listed and transplanted fewer: respectively 36% vs. 20%, p = 0.012. Conclusion: Patients with ACLF-3 face inequity of access to LT across Europe. Wait-listing strategies for ACLF-3 patients influence their access to LT and, ultimately, their survival.

Published
2022

18. Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis

Author

Tranah T, Ballester M, Carbonell-Asins J, Ampuero J, Alexandrino G, Caracostea A, Sanchez-Torrijos Y, Thomsen K, Kerbert A, Capilla-Lozano M, Romero-Gomez M, Escudero-Garcia D, Montoliu C, Jalan R, and Shawcross D

Abstract

BACKGROUND AND AIMS: Hyperammonaemia is central in the pathogenesis of hepatic encephalopathy, but also has pleiotropic deleterious effects on several organ systems, impacting on immune function, sarcopenia, energy metabolism and portal hypertension. This study was performed to test the hypothesis that severity of hyperammonaemia is a risk factor for liver-related complications in clinically stable outpatients with cirrhosis.; METHODS: We collected data from 754 clinically stable outpatients with cirrhosis from 3 independent liver units. Baseline ammonia levels were corrected to the upper limit of normal (AMM-ULN) for the reference laboratory. The primary endpoint was hospitalisation with liver-related complications (a composite endpoint of bacterial infection, variceal bleeding, overt hepatic encephalopathy, or new onset or worsening of ascites). Multivariable competing risk frailty analysis and fast unified random forest were performed to predict complications and mortality. External validation was carried out using prospective data from 130 cirrhotic patients in an independent tertiary liver centre.; RESULTS: Overall, 260 (35%) patients were hospitalised with liver-related complications. On multivariable analysis, AMM-ULN was an independent predictor of both liver-related complications (HR=2.13; 95%CI=1.89-2.40; p

Published
2022

31. Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis

Author

Stadlbauer, V., Mookerjee, R.P., Wright, G.A.K., Davies, N.A., Jurgens, G., Hallstrom, S., and Jalan, R.

Subjects
Hepatitis, Alcoholic -- Complications and side effects, Hepatitis, Alcoholic -- Genetic aspects, Cell receptors -- Physiological aspects, Cell receptors -- Genetic aspects, Cell receptors -- Research, Neutrophilia -- Risk factors, Neutrophilia -- Genetic aspects, Neutrophilia -- Control, Neutrophilia -- Research, Biological sciences
Abstract

Neutrophil dysfunction in alcoholic hepatitis is associated with endotoxemia and an increased incidence of infection, but the mechanism is unclear. We aimed to investigate the role of Toll-like-receptors (TLR)2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis. Neutrophils from healthy volunteers were incubated with alcoholic hepatitis patients' plasma (n = 12) with and without TLR2, 4, or 9 antagonists and with and without human albumin. TLR2, 4, and 9 expression, neutrophil oxidative burst, phagocytosis, and CXCR1 + 2 expression were measured by FACS analysis. Patients' plasma increased oxidative burst, decreased CXCR1 + 2 expression, and decreased phagocytosis of normal neutrophils in association with increased expression of TLR2, 4, and 9 and depletion of ATP. Inhibition of TLR2, 4, and 9 prevented the increase in oxidative burst and the decrease in CXCR1 and CXCR2 expression but did not prevent phagocytic dysfunction. Incubation with albumin completely prevented the patient plasma induced neutrophil dysfunction. Increased expression of TLR2, 4, and 9 is associated with neutrophil dysfunction, endotoxemia, and energy depletion. TLR2, 4, and 9 inhibition does not improve phagocytosis, indicating that TLR overexpression may be the result and not the cause of neutrophil activation. Albumin, an endotoxin scavenger, prevents the deleterious effect of patients' plasma on neutrophil phagocytosis, resting burst, and TLR expression. alcoholic liver disease; immune function: endotoxin; acute on chronic liver failure; chemokines

Published
2009

34. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF (vol 72, pg 688, 2020)

Author

Moreau, R, Claria, J, Aguilar, F, Fenaille, F, Lozano, JJ, Junot, C, Colsch, B, Caraceni, P, Trebicka, J, Pavesi, M, Alessandria, C, Nevens, F, Saliba, F, Welzel, TM, Albillos, A, Gustot, T, Fernandez, J, Moreno, C, Baldassarre, M, Zaccherini, G, Piano, S, Montagnese, S, Vargas, V, Genesca, J, Sola, E, Bernal, W, Butin, N, Hautbergue, T, Cholet, S, Castelli, F, Jansen, C, Steib, C, Campion, D, Mookerjee, R, Rodriguez-Gandia, M, Soriano, G, Durand, F, Benten, D, Banares, R, Stauber, RE, Gronbaek, H, Coenraad, MJ, Gines, P, Gerbes, A, Jalan, R, Bernardi, M, Arroyo, V, Angeli, P, CANONIC Study, and Grifols Chair European

Published
2020
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35. Recent advances in understanding and managing hepatic encephalopathy in chronic liver disease

Author

Jalan R and Kerbert Ajc

Subjects
0301 basic medicine, medicine.medical_specialty, hyperammonemia, Review, Chronic liver disease, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Ammonia, medicine, Humans, Routine clinical practice, General Pharmacology, Toxicology and Pharmaceutics, Intensive care medicine, Hepatic encephalopathy, Severe complication, Inflammation, General Immunology and Microbiology, business.industry, Treatment options, chronic liver disease, Hyperammonemia, General Medicine, Articles, medicine.disease, Review article, 030104 developmental biology, Hepatic Encephalopathy, Quality of Life, 030211 gastroenterology & hepatology, business
Abstract

Hepatic encephalopathy (HE) is a common, severe complication of advanced chronic liver disease (CLD) and has a devastating impact on the patient’s quality of life and prognosis. The neurotoxin ammonia and the presence of systemic and neurological inflammation are considered the key drivers of this neuropsychiatric syndrome. Treatment options available in routine clinical practice are limited, and the development of novel therapies is hampered owing to the complexity and heterogeneity of HE. This review article aims to outline the current understanding of the pathomechanisms of HE and the recent advances in the identification and development of novel therapeutic targets.

Published
2020

36. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author

Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Belli, Luca S, Duvoux, Christophe, Artzner, Thierry, Bernal, William, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie-Caroline, Pageaux, George-Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, Francoise, Rabinovich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Fondevila, Costantino, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Jalan, Rajiv, FAGIUOLI, STEFANO, Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Belli, Luca S, Duvoux, Christophe, Artzner, Thierry, Bernal, William, Conti, Sara, Cortesi, Paolo A, Sacleux, Sophie-Caroline, Pageaux, George-Philippe, Radenne, Sylvie, Trebicka, Jonel, Fernandez, Javier, Perricone, Giovanni, Piano, Salvatore, Nadalin, Silvio, Morelli, Maria C, Martini, Silvia, Polak, Wojciech G, Zieniewicz, Krzysztof, Toso, Christian, Berenguer, Marina, Iegri, Claudia, Invernizzi, Federica, Volpes, Riccardo, Karam, Vincent, Adam, René, Faitot, Francoise, Rabinovich, Liane, Saliba, Faouzi, Meunier, Lucy, Lesurtel, Mickael, Uschner, Frank E, Fondevila, Costantino, Michard, Baptiste, Coilly, Audrey, Meszaros, Magdalena, Poinsot, Domitille, Schnitzbauer, Andreas, De Carlis, Luciano G, Fumagalli, Roberto, Angeli, Paolo, Arroyo, Vincente, Jalan, Rajiv, and FAGIUOLI, STEFANO

Abstract

Background and aims: Liver transplantation (LT) has been proposed to be an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to address the current clinical practice and outcomes of ACLF patients wait listed (WL) for LT in Europe. Methods: Retrospective study including 308 consecutive ACLF patients, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: 2677 patients received a LT, 1216 (45.4%) for decompensated cirrhosis (DC). Of these, 234 (19.2%) had ACLF at LT: ACLF-1, 58 (4.8%); ACLF-2, 78 (6.4%); and ACLF-3, 98 (8.1%). Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and Netherlands had medium rates (9-15%); and United Kingdom and Spain had low rates (3-5%) (p <.0001). One-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (HR 3.14, 95% CI 1.37-7.19), recent infection from multi-drug resistant organisms (HR 3.67, 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74, 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the WL. In an intention-to-treat analysis, one-year survival of ACLF patients on the LT WL was 73% for ACLF-1 or -2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in listing patients with ACLF in Europe despite favorable post-LT survival. Risk factors for mortality were identified, allowing a more precise prognostic assessment of ACLF patients for potential LT. Lay summary: Acute on chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonized to avoid inequities.

Published
2021

40. Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia

Author

Shawcross, D.L., Balata, S., Damink, S.W.M. Olde, Hayes, P.C., Wardlaw, J., Marshall, I., Deutz, N.E.P., Williams, R., and Jalan, R.

Subjects
Brain -- Research, Brain -- Physiological aspects, Neuropsychology -- Research, Neuropsychology -- Physiological aspects, Liver cirrhosis -- Research, Liver cirrhosis -- Physiological aspects, Biological sciences
Abstract

The neuropsychological effect of hyperammonemia is variable. This study tests the hypothesis that the effect of ammonia on the neuropsychological function in patients with cirrhosis is determined by the ability of the brain to buffer ammonia-induced increase in glutamine within the astrocyte by losing osmolytes like myo-inositol (mI) and not by the magnitude of the induced hyperammonemia. Fourteen cirrhotic patients with no evidence of overt hepatic encephalopathy were given a 75-g amino acid (aa) solution mimicking the hemoglobin molecule to induce hyperammonemia. Measurement of a battery of neuropsychological function tests including immediate memory, ammonia, aa, and short-echo time proton magnetic resonance spectroscopy were performed before and 4 h after administration of the aa solution. Eight patients showed deterioration in the Immediate Memory Test at 4 h. Demographic factors, severity of liver disease, change in plasma ammonia, and aa profiles after the aa solution were similar in those that showed a deterioration compared with those who did not. In patients who showed deterioration in the memory test, the mI-to-creatine ratio (mI/Cr) was significantly lower at baseline than those that did not deteriorate. In contrast, the glutamate/glutamine-to-Cr ratio was significantly greater in the patients that deteriorated. The observation that deterioration in the memory test scores was greater in those with lower mI/Cr supports the hypothesis that the neuropsychological effects of induced hyperammonemia is determined by the capacity of the brain to handle ammonia-induced increase in glutamine. neuropsychological function; amino acid solution; magnetic resonance spectroscopy; hepatic encephalopathy

Published
2004

41. Prospects for extracorporeal liver support

Author

Jalan, R., Sen, S., and Williams, R.

Subjects
Liver failure -- Care and treatment, Artificial liver -- Research, Health
Abstract

The goals of artificial liver support, the design of the existing liver support systems and the current status in the management of patients with liver failure are discussed. The molecular recirculating system (MARS) is increasingly used for the management of liver failure.

Published
2004

42. Randomised controlled trial of long term portographic follow up versus variceal band ligation following transjugular intrahepatic portosystemic stent shunt for preventing oesophageal variceal rebleeding

Author

Tripathi, D., Lui, H.F., Helmy, A., Dabos, K., Forrest, E., Stanley, A.J., Jalan, R., and Redhead, D.N.

Abstract

Gut 2004;53:431-437. doi: 10.1136/gut.2003.013532 Background/aims: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims [...]

Published
2004

43. Tumour necrosis factor α is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis

Author

Mookerjee, RP, Sen, S, Davies, NA, Hodges, SJ, Williams, R, and Jalan, R

Subjects
Care and treatment, Physiological aspects, Tumor necrosis factor -- Physiological aspects, Venous pressure -- Physiological aspects, Alcoholic hepatitis -- Care and treatment -- Physiological aspects, Statistics (Data) -- Physiological aspects, Statistics -- Physiological aspects, Hepatitis, Alcoholic -- Care and treatment -- Physiological aspects
Abstract

Background: The role of proinflammatory cytokines in the pathogenesis of portal hypertension is unclear. Aims and methods: This study tests the hypothesis that tumour necrosis factor α (TNF-α) is an [...]

Published
2003

44. Enhanced renal ammonia excretion following volume expansion in patients with well compensated cirrhosis of the liver. (Liver)

Author

Jalan, R. and Kapoor, D.

Subjects
Care and treatment, Evaluation, Physiological aspects, Dosage and administration, Saline injections -- Dosage and administration -- Evaluation -- Physiological aspects, Liver cirrhosis -- Care and treatment, Urogenital system -- Physiological aspects, Injections, Saline -- Dosage and administration -- Evaluation -- Physiological aspects, Genitourinary organs -- Physiological aspects
Abstract

Background and aims: In patients with cirrhosis, hepatic encephalopathy is often precipitated by dehydration. This study tests the hypothesis that volume expansion in cirrhotic patients increases renal ammonia excretion. Patients [...]

Published
2003

45. Enhanced vasodilatation to endothelin antagonism in patients with compensated cirrhosis and the role of nitric oxide. (Liver Disease)

Author

Helmy, A., Newby, D.E., Jalan, R., Hayes, P.C., and Webb, D.J.

Subjects
Physiological aspects, Endothelin -- Physiological aspects, Nitric oxide -- Physiological aspects, Liver cirrhosis -- Physiological aspects
Abstract

Background and aims: Patients with advanced cirrhosis have systemic vasodilatation and increased nitric oxide (NO) production despite activated vasopressor systems, including the endothelin system. The aims of this study were [...]

Published
2003

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