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1. Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis

Author

Kang Zheng, Fengjie Hao, Sandra Medrano-Garcia, Chaobo Chen, Feifei Guo, Laura Morán-Blanco, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, María Isabel Peligros, Javier Vaquero, Rafael Bañares, Manuel Gómez del Moral, José R. Regueiro, Eduardo Martínez-Naves, Mohamed Ramadan Mohamed, Rocío Gallego-Durán, Douglas Maya, Javier Ampuero, Manuel Romero-Gómez, Albert Gilbert-Ramos, Sergi Guixé-Muntet, Anabel Fernández-Iglesias, Jordi Gracia-Sancho, Mar Coll, Isabel Graupera, Pere Ginès, Andreea Ciudin, Jesús Rivera-Esteban, Juan M. Pericàs, María Dolores Frutos, Bruno Ramos Molina, José María Herranz, Matías A. Ávila, Yulia A. Nevzorova, Edgar Fernández-Malavé, and Francisco Javier Cubero

Subjects
Cytology, QH573-671
Abstract

Abstract Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Published
2023
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2. Personalised human albumin in patients with cirrhosis and ascites: design and rationale for the ALB-TRIAL - a randomised clinical biomarker validation trial

Author

Torben Hansen, Pere Ginès, Wim Laleman, Peer Bork, Vishal C Patel, Debbie Shawcross, Robert Schierwagen, Camila Alvarez-Silva, Florence Servant, Jonel Trebicka, Benjamin Lelouvier, Manimozhiyan Arumugam, Ed J Kuijper, Frank Erhard Uschner, Michael Praktiknjo, Mária Papp, Saeed Shoaie, Michael Kühn, Maja Thiele, Paolo Angeli, Joan Claria, Vicente Arroyo, Manolo Laiola, Benoit Quinquis, Sabine Klein, Minneke J Coenraad, François Fenaille, Debbie Lindsay Shawcross, Wenyi Gu, Adria Juanola, Elisa Pose, Aleksander Krag, Ivica Letunic, Alain Pruvost, Hervé M Blottière, Nathalie Galleron, Cristina López-Vicario, Peter V Treit, Matthias Mann, Jelle Matthijnssens, Mark J W Mcphail, Philipp E Geyer, Hans Olav Melberg, Stefanie Kandels, Cristina Sánchez-Garrido, Florence A Castelli, Christophe Junot, Lars Asphaug, Mads Israelsen, Helene Bæk Juel, Nikolaj Torp, Minneke Coenraad, Marko Korenjak, Ferran Aguilar-Parera, Patricia Sierra-Casas, Anna Bosch-Comas, David Tornai, Boglarka Balogh, Katrine Holtz Thorhauge, Casper Sahl Poulsen, Thea Van Rossum, Suguru Nishijima, Marisa I Keller, Diënty H M Hazenbrink, Sylvain Dechaumet, Sebastian D Burz, Emeline Chu-Van, Etienne Thévenot, Florian A Rosenberger, Sebastian Van Blerk, Amirouche Ouzerdine, Alain Roulet, Jean-Louis-Marie Insonere, Céline Serres, Mathieu Almeida, Florence Thirion, Camille Champion, Chaima Ezzine, Célia Chamignon, Nicolas Lapaque, Mamadou Gabou Thiam, Lore Van Espen, Quinten R Ducarmon, Annelotte GC Broekhoven, Susan Fischer, Romy Zwittink, Itziar De Lecuona, Giulio Rosati, Celia Fuentes-Chust, Arben Merkoçi, Massimo Urban, José Alfonso Marrugo-Ramirez, Ameli Schwalber, Lindsey Ann Edwards, Victoria Tatiana Kronsten, David Moyes, Azadeh Harzandi, Jordi Gratacós-Ginès, Martina Pérez-Guasch, Miriam Pellón, Bryan Contreras, Max Brol, Manfred Fobker, and Renata Antonina Feuerborn

Subjects
Medicine
Abstract

Introduction Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysis ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and dissemination The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion.Trial registration number NCT05056220 EU CT: 2022-501006-34-01

Published
2024
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3. Therapeutic targeting of adipose tissue macrophages ameliorates liver fibrosis in non-alcoholic fatty liver disease

Author

Celia Martínez–Sánchez, Octavi Bassegoda, Hongping Deng, Xènia Almodóvar, Ainitze Ibarzabal, Ana de Hollanda, Raquel–Adela Martínez García de la Torre, Delia Blaya, Silvia Ariño, Natalia Jiménez-Esquivel, Beatriz Aguilar-Bravo, Julia Vallverdú, Carla Montironi, Oscar Osorio-Conles, Yiliam Fundora, Francisco Javier Sánchez Moreno, Alicia G. Gómez-Valadés, Laia Aguilar-Corominas, Anna Soria, Elisa Pose, Adrià Juanola, Marta Cervera, Martina Perez, Virginia Hernández-Gea, Silvia Affò, Kelly S. Swanson, Joana Ferrer-Fàbrega, Jose Maria Balibrea, Pau Sancho-Bru, Josep Vidal, Pere Ginès, Andrew M. Smith, Isabel Graupera, and Mar Coll

Subjects
Dextran dexamethasone conjugates, Non-alcoholic steatohepatitis, Liver injury, Adipose tissue inflammation, Nanoparticle, Nanomedicine, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: : The accumulation of adipose tissue macrophages (ATMs) in obesity has been associated with hepatic injury. However, the contribution of ATMs to hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Herein, we investigate the relationship between ATMs and liver fibrosis in patients with patients with NAFLD and evaluate the impact of modulation of ATMs over hepatic fibrosis in an experimental non-alcoholic steatohepatitis (NASH) model. Methods: Adipose tissue and liver biopsies from 42 patients with NAFLD with different fibrosis stages were collected. ATMs were characterised by immunohistochemistry and flow cytometry and the correlation between ATMs and liver fibrosis stages was assessed. Selective modulation of the ATM phenotype was achieved by i.p. administration of dextran coupled with dexamethasone in diet-induced obesity and NASH murine models. Chronic administration effects were evaluated by histology and gene expression analysis in adipose tissue and liver samples. In vitro crosstalk between human ATMs and hepatic stellate cells (HSCs) and liver spheroids was performed. Results: Patients with NAFLD presented an increased accumulation of pro-inflammatory ATMs that correlated with hepatic fibrosis. Long-term modulation of ATMs significantly reduced pro-inflammatory phenotype and ameliorated adipose tissue inflammation. Moreover, ATMs modulation was associated with an improvement in steatosis and hepatic inflammation and significantly reduced fibrosis progression in an experimental NASH model. In vitro, the reduction of the pro-inflammatory phenotype of human ATMs with dextran–dexamethasone treatment reduced the secretion of inflammatory chemokines and directly attenuated the pro-fibrogenic response in HSCs and liver spheroids. Conclusions: Pro-inflammatory ATMs increase in parallel with fibrosis degree in patients with NAFLD and their modulation in an experimental NASH model improves liver fibrosis, uncovering the potential of ATMs as a therapeutic target to mitigate liver fibrosis in NAFLD. Impact and implications: We report that human adipose tissue pro-inflammatory macrophages correlate with hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Furthermore, the modulation of adipose tissue macrophages (ATMs) by dextran-nanocarrier conjugated with dexamethasone shifts the pro-inflammatory phenotype of ATMs to an anti-inflammatory phenotype in an experimental murine model of non-alcoholic steatohepatitis. This shift ameliorates adipose tissue inflammation, hepatic inflammation, and fibrosis. Our results highlight the relevance of adipose tissue in NAFLD pathophysiology and unveil ATMs as a potential target for NAFLD.

Published
2023
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4. Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites

Author

Guillermo Fernández-Varo, Wladimiro Jiménez, Edward Cable, Pere Ginès, Geoff Harris, and Stan Bukofzer

Subjects
In vivo, Mixed agonist/antagonist, OCE-205, Refractory ascites, Selective partial V1a receptor agonist, Therapeutics. Pharmacology, RM1-950
Abstract

The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration–response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205′s lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.

Published
2023
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5. High frequency of acute decompensation and cancer in patients with compensated cirrhosis due to nonalcoholic fatty liver disease: A retrospective cohort study

Author

Octavi Bassegoda, Jesús Rivera‐Esteban, Isabel Serra, Rosa Morillas, Teresa Broquetas, Mercedes Vergara, Adrià Rodriguez, Carles Aracil, Silvia Virolés, Jose A. Carrión, Albert Pardo, Sergio Rodríguez‐Tajes, Miquel Serra‐Burriel, Juan M. Pericàs, Salvador Augustin, Pere Ginès, and Isabel Graupera

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract The natural history of compensated cirrhosis due to nonalcoholic fatty liver disease (NAFLD) has not been completely characterized. The aim of the present study was to assess the incidence and risk factors of acute decompensation of cirrhosis, hepatocellular carcinoma, and extrahepatic cancers. This was a multicenter, retrospective, cohort study including 449 patients with compensated cirrhosis due to NAFLD. We calculated cumulative incidences and used competitive risk analysis to determine the risk factors associated with decompensation and cancer development. Over a median of 39 months of follow‐up, 124 patients (28%) presented acute decompensation. The most frequent decompensation was ascites (21%) followed by hepatic encephalopathy (15%), variceal bleeding (9%), and spontaneous bacterial peritonitis (3%). Acute‐on‐chronic liver failure was diagnosed in 6% of patients during follow‐up. Liver function parameters and specifically an albumin level below 40 g/L were independently associated with an increased risk of decompensation. The presence of ischemic heart disease was independently associated with acute decompensation. Seventy‐eight patients (18%) developed hepatocellular carcinoma or extrahepatic cancers during follow‐up (51 and 27, respectively). Conclusion: Patients with compensated cirrhosis due to NAFLD are at high risk of severe liver complications, such as the development of acute decompensation, in a relative short follow‐up time. This population is at high risk of hepatic and extrahepatic cancers.

Published
2022
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6. Patterns of kidney dysfunction in acute‐on‐chronic liver failure: Relationship with kidney and patients’ outcome

Author

Laura Napoleone, Cristina Solé, Adrià Juanola, Ann T. Ma, Marta Carol, Martina Pérez‐Guasch, Ana‐Belén Rubio, Marta Cervera, Emma Avitabile, Octavi Bassegoda, Jordi Gratacós‐Ginès, Manuel Morales‐Ruiz, Núria Fabrellas, Isabel Graupera, Elisa Pose, Gonzalo Crespo, Elsa Solà, and Pere Ginès

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Impairment of kidney function is common in acute‐on‐chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill‐defined. Aims of the current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. This prospective study includes 639 admissions for AD (232 with ACLF; 407 without) in 518 patients. Data were collected at admission and during hospitalization, and patients were followed up for 3 months. Urine samples were analyzed for kidney biomarkers. Most patients with ACLF (92%) had associated acute kidney injury (AKI), in most cases without previous chronic kidney disease (CKD), whereas some had AKI‐on‐CKD (70% and 22%, respectively). Prevalence of AKI in patients without ACLF was 35% (p

Published
2022
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7. LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Author

Isabel Graupera, Maja Thiele, Ann T. Ma, Miquel Serra-Burriel, Judit Pich, Núria Fabrellas, Llorenç Caballeria, Robert J. de Knegt, Ivica Grgurevic, Mathias Reichert, Dominique Roulot, Jörn M. Schattenberg, Juan M. Pericas, Paolo Angeli, Emmanuel A. Tsochatzis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosa M. Morillas, Rosario Hernández, Jordi Hoyo, Matilde Fuentes, Anita Madir, Adrià Juanola, Anna Soria, Marta Juan, Marta Carol, Alba Diaz, Sönke Detlefsen, Pere Toran, Guillem Pera, Céline Fournier, Anne Llorca, Phillip N. Newsome, Michael Manns, Harry J. de Koning, Feliu Serra-Burriel, Fernando Cucchietti, Anita Arslanow, Marko Korenjak, Laurens van Kleef, Josep Lluis Falcó, Patrick S. Kamath, Tom H. Karlsen, Laurent Castera, Frank Lammert, Aleksander Krag, Pere Ginès, and for the LiverScreen Consortium investigators

Subjects
Cirrhosis, Screening, Liver fibrosis, Chronic liver disease, NAFLD, NASH, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Published
2022
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8. Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

Author

Elisa Pose, Elsa Solà, Juan J. Lozano, Adrià Juanola, Julia Sidorova, Giacomo Zaccherini, Koos deWit, Frank Uschner, Marta Tonon, Konstantin Kazankov, Cesar Jiménez, Daniela Campion, Laura Napoleone, Ann T. Ma, Marta Carol, Manuel Morales‐Ruiz, Carlo Alessandria, Ulrich Beuers, Paolo Caraceni, Claire Francoz, François Durand, Rajeshwar P. Mookerjee, Jonel Trebicka, Victor Vargas, Salvatore Piano, Hugh Watson, Juan G. Abraldes, Patrick S. Kamath, Mark M. Davis, Pere Ginès, and for the investigators of the LIVERHOPE Consortium

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Published
2022
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9. Correction: LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Author

Isabel Graupera, Maja Thiele, Ann T. Ma, Miquel Serra-Burriel, Judit Pich, Núria Fabrellas, Llorenç Caballeria, Robert J. de Knegt, Ivica Grgurevic, Mathias Reichert, Dominique Roulot, Jörn M. Schattenberg, Juan M. Pericas, Paolo Angeli, Emmanuel A. Tsochatzis, Indra Neil Guha, Montserrat Garcia-Retortillo, Rosa M. Morillas, Rosario Hernández, Jordi Hoyo, Matilde Fuentes, Anita Madir, Adrià Juanola, Anna Soria, Marta Juan, Marta Carol, Alba Diaz, Sönke Detlefsen, Pere Toran, Guillem Pera, Céline Fournier, Anne Llorca, Phillip N. Newsome, Michael Manns, Harry J. de Koning, Feliu Serra-Burriel, Fernando Cucchietti, Anita Arslanow, Marko Korenjak, Laurens van Kleef, Josep Lluis Falcó, Patrick S. Kamath, Tom H. Karlsen, Laurent Castera, Frank Lammert, Aleksander Krag, Pere Ginès, and for the LiverScreen Consortium investigators

Subjects
Public aspects of medicine, RA1-1270
Published
2023
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10. Impact of the COVID-19 pandemic on the care and outcomes of people with NAFLD-related cirrhosis

Author

Jesús Rivera-Esteban, Ramiro Manzano-Nuñez, Teresa Broquetas, Isabel Serra-Matamala, Octavi Bassegoda, Agnès Soriano-Varela, Gemma Espín, Joaquín Castillo, Juan Bañares, José A. Carrión, Pere Ginès, Isabel Graupera, and Juan M. Pericàs

Subjects
Nonalcoholic fatty liver disease, cirrhosis, COVID-19, health systems, liver outcomes, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: The COVID-19 pandemic has had a major negative impact on health systems and many chronic diseases globally. We aimed to evaluate the impact of the first year of the pandemic on the outcomes of people with NAFLD cirrhosis. Methods: We conducted a before-after study in four University hospitals in Catalonia, Spain. Study subperiods were divided into Pre-pandemic (March/2019–February/2020) vs. Pandemic (March/2020–February/2021). The primary outcome was the rate of first liver-related event (LRE). Overall clinical outcomes (LREs plus cardiovascular plus all-cause mortality) were also assessed. Results: A total of 354 patients were included, all of whom were compensated at the beginning of the study period; 83 individuals (23.5%) had a history of prior hepatic decompensation. Mean age was 67.3 years and 48.3% were female. Median BMI was 31.2 kg/m2 and type 2 diabetes was present in 72.8% of patients. The rates of first LRE in the Pre-pandemic and Pandemic periods were 7.4% and 11.3% (p = 0.12), respectively. Whilst the rate of overall events was significantly higher in the Pandemic period (9.9% vs. 17.8%; p = 0.009), this was strongly associated with COVID-19-related deaths. The rate of worsened metabolic status was significantly higher in the Pandemic period (38.4% vs. 46.1%; p = 0.041), yet this was not associated with the risk of first LRE during the Pandemic period, whereas type 2 diabetes (odds ratio [OR] 3.77; 95% CI 1.15–12.32; p = 0.028), albumin 2.67 (OR 15.74; 95% CI 2.01–123.22; p = 0.009) were identified as risk factors in the multivariable analysis. Conclusion: Overall, people with NAFLD cirrhosis did not present poorer liver-related outcomes during the first year of the pandemic. Health system preparedness seems key to ensure that people with NAFLD cirrhosis receive appropriate care during health crises. Lay summary: Mobility restrictions and social stress induced by the COVID-19 pandemic have led to increased alcohol drinking and worsened metabolic control (e.g., weight gain, poor control of diabetes) in a large proportion of the population in many countries. We aimed to analyze whether people with cirrhosis due to non-alcoholic fatty liver disease, who are particularly vulnerable to such lifestyle modifications, were significantly impacted during the first year of the pandemic. We compared the clinical situation of 354 patients one year before the pandemic and one year after. We found that although metabolic control was indeed worse after the first year of the pandemic and patients presented worse clinical outcomes, the latter was mostly due to non-liver causes, namely COVID-19 itself. Moreover, the care provided to these patients did not worsen during the first year of the pandemic.

Published
2022
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11. Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure

Author

Isabel Graupera, Laura Isus, Mar Coll, Elisa Pose, Alba Díaz, Julia Vallverdú, Teresa Rubio-Tomás, Celia Martínez-Sánchez, Patricia Huelin, Marta Llopis, Cristina Solé, Elsa Solà, Constantino Fondevila, Juan José Lozano, Pau Sancho-Bru, Pere Ginès, and Patrick Aloy

Subjects
chronic liver disease, ACLF, network biology, temporal gene expression profile, biomarker, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: The molecular mechanisms driving the progression from early-chronic liver disease (CLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Our aim was to develop a protein network-based approach to investigate molecular pathways driving progression from early-CLD to ACLF. Methods: Transcriptome analysis was performed on liver biopsies from patients at different liver disease stages, including fibrosis, compensated cirrhosis, decompensated cirrhosis and ACLF, and control healthy livers. We created 9 liver-specific disease-related protein-protein interaction networks capturing key pathophysiological processes potentially related to CLD. We used these networks as a framework and performed gene set-enrichment analysis (GSEA) to identify dynamic gene profiles of disease progression. Results: Principal component analyses revealed that samples clustered according to the disease stage. GSEA of the defined processes showed an upregulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between compensated and decompensated cirrhosis, while ACLF showed acute expression changes in all the defined liver disease-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated with ACLF onset. Functional analyses showed that ascending profiles were associated with inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the upregulation of genes of the ascending profile and validated our findings in an independent patient cohort. Conclusion: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting the hypothesis that ACLF should be considered a distinct entity. Lay summary: By using transjugular biopsies obtained from patients at different stages of chronic liver disease, we unveil the molecular pathogenic mechanisms implicated in the progression of chronic liver disease to cirrhosis and acute-on-chronic liver failure. The most relevant finding in this study is that patients with acute-on-chronic liver failure present a specific hepatic gene expression pattern distinct from that of patients at earlier disease stages. This gene expression pattern is mostly related to inflammation, fibrosis, angiogenesis, and senescence and apoptosis pathways in the liver.

Published
2022
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12. Stigmatization is common in patients with non-alcoholic fatty liver disease and correlates with quality of life.

Author

Marta Carol, Martina Pérez-Guasch, Elsa Solà, Marta Cervera, Sara Martínez, Adrià Juanola, Ann T Ma, Emma Avitabile, Laura Napoleone, Elisa Pose, Isabel Graupera, Maria Honrubia, Marko Korenjak, Ferran Torres, Pere Ginès, Núria Fabrellas, and LiverHope Consortium Investigators

Subjects
Medicine, Science
Abstract

Background and aimsStigmatization is a well-documented problem of some diseases. Perceived stigma is common in alcohol-related liver disease and hepatitis C, but little information exists on stigma in patients with non-alcoholic fatty liver disease (NAFLD). Aim of the study was to investigate frequency and characteristics of perceived stigma among patients with NAFLD.MethodsOne-hundred and ninety-seven patients seen at the liver clinic were included: a study group of 144 patients with NAFLD, 50 with cirrhosis (34 compensated, 16 decompensated), and a control group of 53 patients with alcohol-related cirrhosis. Demographic, clinical, and laboratory data were collected. Quality-of-life was assessed by chronic liver disease questionnaire (CLDQ). Perceived stigma was assessed using a specific questionnaire for patients with liver diseases categorized in 4 domains: stereotypes, discrimination, shame, and social isolation.ResultsPerceived stigma was common in patients with NAFLD (99 patients, 69%) and affected all 4 domains assessed. The frequency was slightly higher, yet not significant, in patients with NAFLD cirrhosis vs those without (72% vs 67%, respectively; p = 0.576). In patients without cirrhosis perceived stigma was unrelated to stage of disease, since frequency was similar in patients with no or mild fibrosis compared to those with moderate/severe fibrosis (66% vs 68%, respectively). There were no differences in perceived stigma between patients with compensated cirrhosis and these with decompensated cirrhosis. Among patients with cirrhosis, stigmatization was more common in alcohol-related vs NAFLD-cirrhosis, yet differences were only significant in two domains. In patients with NAFLD, perceived stigma correlated with poor quality-of-life, but not with demographic or clinical variables.ConclusionsPerceived stigmatization is common among patients with NAFLD independently of disease stage, is associated with impaired quality-of-life, and may be responsible for stereotypes, discrimination, shame, and social isolation, which may affect human and social rights of affected patients.

Published
2022
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13. Metabolomics Discloses a New Non-invasive Method for the Diagnosis and Prognosis of Patients with Alcoholic Hepatitis

Author

Javier Michelena, Cristina Alonso, Ibon Martínez-Arranz, José Altamirano, Rebeca Mayo, Pau Sancho-Bru, Ramón Bataller, Pere Ginès, Azucena Castro, and Juan Caballería

Subjects
Alcoholic hepatitis, Metabolomics, Non-invasive diagnosis, Prognosis, Lipidomics, Specialties of internal medicine, RC581-951
Abstract

Introduction and aims. Alcoholic hepatitis is the most severe manifestation of alcoholic liver disease. Unfortunately, there are still some unresolved issues in the diagnosis and management of this disease, such as the need of histological diagnosis, an accurate prognostic stratification, and the development of novel targeted therapies. The present study aimed at addressing these issues by means of metabolomics, a novel high-throughput approach useful in other liver diseases.Material and methods. 64 patients with biopsy-proven alcoholic hepatitis were included and compared with 26 patients with decompensated alcoholic cirrhosis without superimposed alcoholic hepatitis, which was ruled out by liver biopsy.Results. The comparison of the metabolic profiles of patients with alcoholic hepatitis and decompensated cirrhosis showed marked differences between both groups. Importantly, metabolic differences were found among alcoholic hepatitis patients when subjects were stratified according to 90-day survival. Based on these findings, two non-invasive signatures were developed. The first one allowed an accurate non-invasive diagnosis of alcoholic hepatitis (AUROC 0.932; 95% CI 0.901-0.963). The second signature showed a good performance in the prognostic stratification of patients with alcoholic hepatitis (AUROC 0.963; 95% CI 0.895-1.000).Conclusions. Signatures based on metabolomics allowed an accurate non-invasive diagnosis and prognostic stratification of alcoholic hepatitis. The differences observed in the metabolic profile of the patients according to the presence and severity of alcoholic hepatitis are related with different mechanisms involved in the pathophysiology of alcoholic hepatitis such as peroxisomal activity, synthesis of inflammatory mediators or oxidation. This information could be useful for the development of novel targeted therapies.

Published
2019
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14. Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure

Author

Delia Blaya, Elisa Pose, Mar Coll, Juan José Lozano, Isabel Graupera, Robert Schierwagen, Christian Jansen, Pedro Castro, Sara Fernandez, Julia Sidorova, Mariuca Vasa-Nicotera, Elsa Solà, Joan Caballería, Jonel Trebicka, Pere Ginès, and Pau Sancho-Bru

Subjects
Liver decompensation, Non-coding RNAs, Biomarkers, Chronic liver disease, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: MicroRNAs (miRNAs) circulate in several body fluids and can be useful biomarkers. The aim of this study was to identify blood-circulating miRNAs associated with cirrhosis progression and acute-on-chronic liver failure (ACLF). Methods: Using high-throughput screening of 754 miRNAs, serum samples from 45 patients with compensated cirrhosis, decompensated cirrhosis, or ACLF were compared with those from healthy individuals (n = 15). miRNA levels were correlated with clinical parameters, organ failure, and disease progression and outcome. Dysregulated miRNAs were evaluated in portal and hepatic vein samples (n = 33), liver tissues (n = 17), and peripheral blood mononuclear cells (PBMCs) (n = 16). Results: miRNA screening analysis revealed that circulating miRNAs are dysregulated in cirrhosis progression, with 51 miRNAs being differentially expressed among all groups of patients. Unsupervised clustering and principal component analysis indicated that the main differences in miRNA expression occurred at decompensation, showing similar levels in patients with decompensated cirrhosis and those with ACLF. Of 43 selected miRNAs examined for differences among groups, 10 were differentially expressed according to disease progression. Moreover, 20 circulating miRNAs were correlated with model for end-stage liver disease and Child-Pugh scores. Notably, 11 dysregulated miRNAs were associated with kidney or liver failure, encephalopathy, bacterial infection, and poor outcomes. The most severely dysregulated miRNAs (i.e. miR-146a-5p, miR-26a-5p, and miR-191-5p) were further evaluated in portal and hepatic vein blood and liver tissue, but showed no differences. However, PBMCs from patients with cirrhosis showed significant downregulation of miR-26 and miR-146a, suggesting a extrahepatic origin of some circulating miRNAs. Conclusions: This study is a repository of circulating miRNA data following cirrhosis progression and ACLF. Circulating miRNAs were profoundly dysregulated during the progression of chronic liver disease, were associated with failure of several organs and could have prognostic utility. Lay summary: Circulating miRNAs are small molecules in the blood that can be used to identify or predict a clinical condition. Our study aimed to identify miRNAs for use as biomarkers in patients with cirrhosis or acute-on-chronic liver failure. Several miRNAs were found to be dysregulated during the progression of disease, and some were also related to organ failure and disease-related outcomes.

Published
2021
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15. Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival

Author

Annarein J. C. Kerbert, Hein W. Verspaget, Àlex Amorós Navarro, Rajiv Jalan, Elsa Solà, Daniel Benten, François Durand, Pere Ginès, Johan J. van der Reijden, Bart van Hoek, Minneke J. Coenraad, and for the CANONIC Study Investigators of the EASL-CLIF Consortium

Subjects
Acute-on-chronic liver failure, Cirrhosis, Organ failure, Biomarker, Copeptin, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. Methods All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0–2, 3–7, 8–14, 15–21, and 22–28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. Results Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0–2 (33 (14–64) vs. 11 (4–26) pmol/L; p

Published
2017
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16. Adipocyte Fatty-Acid Binding Protein is Overexpressed in Cirrhosis and Correlates with Clinical Outcomes

Author

Isabel Graupera, Mar Coll, Elisa Pose, Chiara Elia, Salvatore Piano, Elsa Solà, Delia Blaya, Patricia Huelin, Cristina Solé, Rebeca Moreira, Gloria de Prada, Núria Fabrellas, Adrià Juanola, Manuel Morales-Ruiz, Pau Sancho-Bru, Càndid Villanueva, and Pere Ginès

Subjects
Medicine, Science
Abstract

Abstract Fatty-acid-binding proteins (FABPs) are small intracellular proteins that coordinate lipid-mediated processes by targeting metabolic and immune response pathways. The aim of the study was to investigate plasma FABPs levels and their relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of FABPs was assessed in liver biopsies from patients with decompensated cirrhosis and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4 in human liver biopsy was also performed. Plasma levels of FABPs were increased in patients with decompensated cirrhosis compared to those of healthy subjects (L-FABP1: 25 (17–39) vs 10 (9–17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5–2.1) vs 0.6 (0.4–1) ng/mL p = 0.04 and A-FABP4: 37 (20–68) vs 16 (11–33) ng/mL p = 0.002), respectively. Increased A-FABP4 levels were associated with complications of cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene expression was upregulated in decompensated cirrhosis. Macrophages were the main liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A-FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4 levels are increased in decompensated cirrhosis and correlate with poor outcomes. Liver macrophages appear to be the main source of A-FABP4 in decompensated cirrhosis.

Published
2017
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17. Addressing Profiles of Systemic Inflammation Across the Different Clinical Phenotypes of Acutely Decompensated Cirrhosis

Author

Jonel Trebicka, Alex Amoros, Carla Pitarch, Esther Titos, José Alcaraz-Quiles, Robert Schierwagen, Carmen Deulofeu, Javier Fernandez-Gomez, Salvatore Piano, Paolo Caraceni, Karl Oettl, Elsa Sola, Wim Laleman, Jane McNaughtan, Rajeshwar P. Mookerjee, Minneke J. Coenraad, Tania Welzel, Christian Steib, Rita Garcia, Thierry Gustot, Miguel A. Rodriguez Gandia, Rafael Bañares, Agustin Albillos, Stefan Zeuzem, Victor Vargas, Faouzi Saliba, Frederic Nevens, Carlo Alessandria, Andrea de Gottardi, Heinz Zoller, Pere Ginès, Tilman Sauerbruch, Alexander Gerbes, Rudolf E. Stauber, Mauro Bernardi, Paolo Angeli, Marco Pavesi, Richard Moreau, Joan Clària, Rajiv Jalan, and Vicente Arroyo

Subjects
acute decompensation, cirrhosis, signature, ACLF, organ failure, organ dysfunction, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients.Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine

Published
2019
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18. Prevalence of hepatic steatosis as assessed by controlled attenuation parameter (CAP) in subjects with metabolic risk factors in primary care. A population-based study.

Author

Núria Fabrellas, Rosario Hernández, Isabel Graupera, Elsa Solà, Pilar Ramos, Natividad Martín, Gemma Sáez, Consuelo Simón, Almudena Pérez, Teresa Graell, Andrea Larrañaga, Manel Garcia, Ana de la Arada, Adrià Juanola, Alicia Coiduras, Isabel Duaso, Angel Casado, Julian Martin, Marta Ginès, Nuria Moreno, Ana Gema Perez, Laia Marti, Mireia Bernat, Montse Sola, Carmina Olivé, Cristina Solé, and Pere Ginès

Subjects
Medicine, Science
Abstract

BACKGROUND:Primary care is the ideal setting for early identification of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a potentially progressive disease that may lead to cirrhosis and liver cancer but is frequently underrecognized because subjects at risk are often not evaluated. Controlled attenuation parameter (CAP) is a reliable method for non-invasive quantification of liver fat. It has the advantage of simultaneous measurement of liver stiffness (LS), an estimate of liver fibrosis. There is no information on CAP in subjects with risk factors from primary care. AIM:To investigate the prevalence of hepatic steatosis, as estimated by CAP, in subjects from the community with metabolic risk factors and correlate findings with clinical and biochemical characteristics and LS. PATIENTS AND METHODS:Population-based study of 215 subjects with metabolic risk factors without known liver disease identified randomly from a primary care center. A control group of 80 subjects matched by age and sex without metabolic risk factors was also studied. CAP and LS were assessed using Fibroscan. RESULTS:Subjects with risk factors had CAP values higher than those of control group (268±64 vs 243±49dB/m,p 280dB/m) in subjects with risk factors was 43%. In multivariate analysis, fatty liver index (FLI) and HOMA were independent predictive factors of severe steatosis. There was a direct correlation between CAP and FLI values (r = 0.52,p

Published
2018
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19. Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis.

Author

Isabel Graupera, Elsa Solà, Núria Fabrellas, Rebeca Moreira, Cristina Solé, Patricia Huelin, Gloria de la Prada, Elisa Pose, Xavier Ariza, Alessandro Risso, Sonia Albertos, Manuel Morales-Ruiz, Wladimiro Jiménez, and Pere Ginès

Subjects
Medicine, Science
Abstract

MCP-1 (monocyte chemoattractant protein-1) is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis.To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis.Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN), trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed.69 patients(32%) had at least one readmission during the 3-month period of follow-up and 30 patients died(14%). Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27-2.1) and 2003 (705-4586) ug/g creat vs 0.47 (0.2-1.1) and 1188 (512-2958) ug/g creat, in patients with and without readmission, respectively; p

Published
2016
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20. Hepatic hemodynamics and transient elastography in alcoholic foamy degeneration: report of 2 cases

Author

Pablo Ruiz, Javier Michelena, José Altamirano, Rosa Miquel, Leticia Moreira, Andrés Cárdenas, Juan G. Abraldes, Miquel Brugera, Vicente Arroyo, Pere Ginès, Juan Caballería, and Ramón Bataller

Subjects
Alcoholic liver desease, Fatty liver disease, Steatohepatitis, Cirrhosis, Hepatocellular carcinoma, Specialties of internal medicine, RC581-951
Abstract

Alcoholic liver disease (ALD) covers a wide spectrum of pathology ranging from fatty liver disease to acute steatohepatitis to cirrhosis and/or hepatocellular carcinoma. Alcoholic foamy degeneration (AFD) is an uncommon, potentially life-threatening condition that is part of the spectrum of ALD. It is characterized by extensive microvesicular steatosis in the perivenular areas. Since the first description in 1983, few case reports have been described. Here, we report 2 cases of AFD in patients with a previous history of chronic alcohol abuse and histological diagnosis of AFD with typical clinical, biochemical and histological features. In both cases we provide data on the hepatic hemodynamic status, and in one of them we report liver elastography results, which are features that have not been described previously. In both cases there was rapid resolution of biochemical and clinical abnormalities after complete abstinence, which is the mainstay of treatment for AFD.

Published
2012
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21. Analysis of a urinary biomarker panel for clinical outcomes assessment in cirrhosis.

Author

Xavier Ariza, Elsa Solà, Chiara Elia, Rogelio Barreto, Rebeca Moreira, Manuel Morales-Ruiz, Isabel Graupera, Ezequiel Rodríguez, Patricia Huelin, Cristina Solé, Javier Fernández, Wladimiro Jiménez, Vicente Arroyo, and Pere Ginès

Subjects
Medicine, Science
Abstract

Biomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but information is very limited. Given the large number of biomarkers, adequate choice of which biomarker(s) to investigate first is important.Analysis of potential usefulness of a panel of urinary biomarkers in outcome assessment in cirrhosis.Fifty-five patients with acute decompensation of cirrhosis were studied: 39 had Acute Kidney Injury (AKI) (Prerenal 12, type-1 HRS (hepatorenal syndrome) 15 and Acute Tubular Necrosis (ATN) 12) and 16 acute decompensation without AKI. Thirty-four patients had Acute-on-chronic liver failure (ACLF). A panel of 12 urinary biomarkers was assessed, using a multiplex assay, for their relationship with ATN, ACLF and mortality.Biomarker with best accuracy for ATN diagnosis was NGAL (neutrophil-gelatinase associated lipocalin): 36 [26-125], 104 [58-208] and 1807 [494-3,716] μg/g creatinine in Prerenal-AKI, type-1 HRS and ATN, respectively; p

Published
2015
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22. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

Author

Silvia Affò, Daniel Rodrigo-Torres, Delia Blaya, Oriol Morales-Ibanez, Mar Coll, Cristina Millán, José Altamirano, Vicente Arroyo, Joan Caballería, Ramón Bataller, Pere Ginès, and Pau Sancho-Bru

Subjects
Medicine, Science
Abstract

Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

Published
2015
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23. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials

Author

Gadano, Adrian, Martins, Marcelo, Angus, Peter, Bate, John, Danta, Mark, George, Jacob, Hodge, Alexander, Kontorinis, Nickolas, Roberts, Stuart, Sanagapalli, Santosh, Skoien, Richard, Thompson, Alexander, Zekry, Amany, Stauber, Rudolf, Trauner, Michael, Moreno, Christophe, Reynaert, Hendrik, Verbeke, Len, Silva, Mario Reis Alvares da, Parise, Edison, Oliveira, Claudia Pinto Marques Souza de, Araujo, Roberta Chaves, Martinelli, Ana de Lourdes Candolo, Borman, Meredith, Chandok, Natasha, Elkhashab, Magdy, Fraser, Hughie, Kaita, Kelly, Ma, Mang, Marotta, Paul, Ramji, Alnoor, Tam, Edward, Yoshida, Eric, Swain, Mark, Sebastiani, Giada, Petrunia, Denis, Abergel, Armando, Anty, Rodolphe, Bourlière, Marc, Boursier, Jérôme, Bureau, Christophe, Castera, Laurent, Habersetzer, François, Hézode, Christophe, Ledinghen, Victor De, Leroy, Vincent, Loustaud-Ratti, Véronique, Mathurin, Philippe, Pol, Stanislas, Zoulim, Fabien, Hinrichsen, Holger, Ingiliz, Patrick, Lammert, Frank, Manns, Michael, Schattenberg, Jörn, Schiefke, Ingolf, Trautwein, Christian, Zeuzem, Stefan, Hui, Aric, Li, King-Kong, Wong, Vincent, Acharya, Subrat, Chowdhury, Abhijit, Duseja, Ajay, Kapoor, Dharmesh, Mukewar, Shrikant, Sarin, Shiv, Shah, Samir, Shalimar, Sood, Ajit, Tantry, BV, Ben-Ari, Ziv, Katchman, Helena, Safadi, Rifaat, Veitsman, Ella, Zuckerman, Eli, Brunetto, Maurizia, Lampertico, Pietro, Mangia, Alessandra, Akahane, Takemi, Akuta, Norio, Eguchi, Yuichiro, Fujiyama, Shigetoshi, Genda, Takuya, Hiasa, Yoichi, Ido, Akio, Ikeda, Fusao, Ikegami, Tadashi, Imajo, Kento, Itoh, Yoshito, Iwasa, Motoh, Karino, Yoshiyasu, Kato, Naoya, Kawaguchi, Takumi, Kawanaka, Miwa, Kido, Masahiro, Kobayashi, Tomoo, Kurosaki, Masayuki, Matsuzaki, Yasushi, Mita, Eiji, Mizukoshi, Eishiro, Nakahara, Takashi, Nomura, Hideyuki, Notsumata, Kazuo, Okanoue, Takeshi, Saito, Satoshi, Sakugawa, Hiroshi, Suzuki, Yoshiyuki, Takaguchi, Koichi, Takaki, Akinobu, Takashima, Tomoyuki, Tanaka, Saiyu, Tsuji, Keiji, Ueno, Yoshiyuki, Umemura, Takeji, Uto, Hirofumi, Yamashita, Nobuyuki, Yanase, Mikio, Yatsuhashi, Hiroshi, Yoneda, Masashi, Chan, Wah Kheong, Tan, Soek Siam, Garza, Laura Cisneros, Ladron De Guevara Cetina, Alma, Angeles, Rocio Guadalupe Vargas, Silva, Francisca Martinez, Van Erpecum, Karel, Orr, David, Jabłkowski, Maciej, Jaroszewicz, Jerzy, Ramos, Jose, Ahmed, Taufique, Ang, Tiing, Dan, Yock young, Goh, Boon Bee, Kaliyaperumal, Kalaiyarasi, Yip, Cherng Hann, Baik, Soon Koo, Jang, Byoung Kuk, Jun, Dae Won, Kim, Won, Kim, Hyung Joon, Kim, Ji Hoon, Lee, Kwan Sik, Lee, Chun Kyon, Lim, Young-Suk, Park, Jun Yong, Tak, Won Young, Augustin, Salvador, Perez, Salvador Benlloch, Caballeria, Juan, Luis, Jose, Panero, Calleja, Rodríguez, Jose Carrión, Garcia, Javier Crespo, Samaniego, Javier Garcia, Gibert, Pere Ginès, Prieto, Martin, Gomez, Manuel Romero, Turnes, Juan, Dufour, Jean-Francois, Moriggia, Alberto, Sheen, I-Shyan, Kao, Jia-Horng, Cheng, Pin-Nan, Huang, Jee-Fu, Yang, Sheng-Shun, Su, Wei-Wen, Chen, Chi-Yi, Chien, Rong-Nan, Lo, Gin-Ho, Chu, Chi-Jen, Wang, Horng-Yuan, Hu, Jui-Ting, Huang, Yi Wen, Agarwal, Kosh, Allison, Michael, Anstee, Quentin, Austin, Andrew, Fowell, Andrew, Ch'ng, Chin Lye, Manousou, Pinelopi, Newsome, Philip, Ryder, Stephen, Shankar, Arun, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Alam, Imtiaz, Alba, Laura, Alkhouri, Naim, Allen, Alina, Aqel, Bashar, Balart, Luis, Barritt, A. Sidney, IV, Behari, Jaideep, Bennett, Michael, Bernstein, David, Bhandari, Bal Raj, Bonacini, Maurizio, Borg, Brian, Brown, Kimberly, Bzowej, Natalie, Caldwell, Stephen, Chami, Tawfik, Coates, Allan, Cueli, Adolfo, Davis, Mitchell, deLemos, Andrew, Desai, Archita, Dunn, Winston, Ferreira, Nelson, Fine, Michael, Firpi-Morell, Roberto, Freedland, Curtis, Freilich, Bradley, Fuchs, Michael, Galambos, Michael, Gallegos-Orozco, Juan, Galler, Greg, Ghali, Maged, Ghalib, Reem, Gill, Satinder, Gillis, Marcum, Gilroy, Richard, Gordon, Stuart, Gunn, Nadege, Halegoua-DeMarzio, Dina, Hassan, Mohamed, Hassanein, Tarek, Herring, Robert, Jr., Hong, John, Huang, Jonathan, Kabler, Heidi, Kayali, Zeid, Knapple, Whitfield, Kolli, Geetha, Kowdley, Kris, Krause, Richard, Lawitz, Eric, Lidofsky, Steven, Lim, Joseph, Lipkis, Donald, Loomba, Rohit, Mahgoub, Amar, Malespin, Miguel, Manch, Richard, Mannis, Steven, Manos, Paul, McDonald, Thomas, McKenzie, Mark, Mena, Edward, Merriman, Raphael, Moehlen, Martin William, Montgomery, Richard, Murphy, Robert, Natarajan, Yamini, Neff, Guy, Noureddin, Mazen, Ortiz-Lasanta, Grisell, Pagadala, Mangesh, Patel, Keyur, Patton, Heather, Peyton, Adam, Pimstone, Neville, Poulos, John, Pound, David, Pyrsopoulos, Nikolaos, Rafiq, Nila, Ravendhran, Natarajan, Ravinuthala, Ravi, Reddy, K. Rajendar, Reindollar, Robert, Reynolds, Justin, Rinella, Mary, Rizvi, Syed, Rockey, Don, Rodriguez-Perez, Federico, Ruane, Peter, Rubin, Raymond, Ryan, Michael, Saeian, Kia, Sanyal, Arun, Sarkar, Souvik, Scanga, Andrew, Schiff, Eugene, Schmidt, Warren, Schneider, Jeffrey, Sepe, Thomas, Shah, Dhiren, Shaikh, Obaid, Shankar, Uday, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shiffman, Mitchell, Siddique, Asma, Smith, Matthew, Suarez, Rosa, Talal, Andrew, Te, Helen, Tekola, Bezawit, Tetri, Brent, Thuluvath, Paul, Toro, Doris, Torres, Dawn, Trinh, Huy, Trotter, James, Vento, Angel, Vierling, John, Vuppalanchi, Raj, Waters, Michael, Weisberg, Ilan, Wieland, Amanda, Williams, Alonzo, Younes, Ziad, Adams, Leon, Harding, Damian, Hodge, Alex, Kontorinis, Nick, Strasser, Simone, Thompson, Alex, Horsmans, Yves, Steenkiste, Christophe Van, Bailey, Robert, Giard, Jeanne-Marie, Montano-Loza, Aldo, Puglia, Marco, Tsoi, Keith, Larrey, Dominique, Nguyen-Khac, Eric, Ratziu, Vlad, Spengler, Ulrich, Wiegand, Johannes, Hui, Aric Josun, Acharya, Subrat Kumar, Sarin, Shiv Kumar, Tantry, Vishwanath, Braun, Marius, Hazzan, Rawi, Lurie, Yoav, Colombo, Massimo, Fujii, Hideki, Hashimoto, Etsuko, Kato, Masaki, Ogawa, Koji, Takehara, Tetsuo, Tokushige, Katsutoshi, Garza, Laura Esthela Cisneros, Ladrón De Guevara, Alma Laura, Schultz, Michael, Janczewska, Ewa, Toro, Doris H., Jeong, Sook-Hyang, Kim, Yoon Jun, Lee, Jin-Woo, Ang, Tiing Leong, Bee, George Goh Boon, Benlloch, Salvador, Caballería, Juan, Calleja, José Luis, Rodríguez, Jose A. Carrión, Crespo, Javier, Diago, Moises, Fernandez-Rodriguez, Conrado, García-Samaniego, Javier, Ginès, Pere, Romero, Manuel, Dufour, Jean-François, Alazawi, William, Ch'ng, Chin-Lye, Forton, Daniel, Priest, Matthew, Sheridan, David, Ankoma-Sey, Victor, Balakrishnan, Maya, Bambha, Kiran, Barritt, A. Sidney, Bhandari, Bal, Brandman, Danielle, Chang, Charissa, Corey, Kathleen, Feldman, Michael, Gholam, Pierre, Goff, John, Marzio, Dina Halegoua-De, Harrison, Stephen, Hellstern, Paul, Jr., Herring, Robert, Iyer, Rajalakshmi, Jakiche, Antoine, Kohli, Anita, Krok, Karen, Kugelmas, Marcelo, Kumar, Sonal, Lai, Michelle, Mahmoud, Mitchell, Mantry, Parvez, Marsano, Luis, Nguyen, Tuan, Park, James, Patton, Heather M., Pockros, Paul, Reddy, Rajender, Rodriguez, Miguel, Sarles, Harry, Satapathy, Sanjaya, Sedghi, Shahriar, Shah, Nikunj, Sheikh, Muhammad Yasin, Sigal, Samuel, Stanca, Carmen, Steinbook, Michael, Szabo, Gyongyi, Terrault, Norah, Tong, Myron, Victor, David, Zervos, Xaralambos, Harrison, Stephen A., Wong, Vincent Wai-Sun, Caldwell, Stephen H., Shiffman, Mitchell L., Camargo, Marianne, Li, Georgia, Kersey, Kathryn, Jia, Catherine, Zhu, Yanni, Djedjos, C. Stephen, Subramanian, G. Mani, Myers, Robert P., Anstee, Quentin M., Romero-Gomez, Manuel, Goodman, Zachary, Lawitz, Eric J., and Younossi, Zobair

Published
2020
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26. Novel Biomarkers of AKI in Cirrhosis

Author

Adrià, Juanola, Ann T, Ma, Elisa, Pose, and Pere, Ginès

Subjects
Liver Cirrhosis, Hepatorenal Syndrome, Hepatology, Humans, Acute Kidney Injury, Kidney, Biomarkers
Abstract

Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis that is associated with poor outcomes and decreased survival. The definition of AKI in cirrhosis is currently based on changes of serum creatinine levels with respect to baseline values. Differential diagnosis of the causes of AKI is of major relevance, considering that some causes of AKI, such as hepatorenal syndrome, have specific treatment options and different prognosis. Prediction of kidney function recovery and patients' survival is also crucial in this patient population to guide clinical decisions. AKI biomarkers in cirrhosis have emerged as a promising tool for differential diagnosis and prognosis in this situation. There are consistent data showing that some urine biomarkers, particularly neutrophil gelatinase-associated lipocalin, may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. AKI biomarkers may constitute a useful tool for use in differential diagnosis, prognosis of renal function, and survival in patients with cirrhosis. This review focuses on the current state of knowledge and future perspective of novel biomarkers of AKI in cirrhosis.

Published
2022

28. Adding Inflammatory Markers and Refining National Institute on Alcohol Abuse and Alcoholism Criteria Improve Diagnostic Accuracy for Alcohol-associated Hepatitis

Author

Emma Avitabile, Alba Díaz, Carla Montironi, Martina Pérez-Guasch, Jordi Gratacós-Ginès, Helena Hernández-Évole, Roger K. Moreira, Tejasav S. Sehrawat, Harmeet Malhi, Pol Olivas, Virginia Hernández-Gea, Ramón Bataller, Vijay H. Shah, Patrick S. Kamath, Pere Ginès, and Elisa Pose

Subjects
Hepatology, Gastroenterology
Published
2023

29. Urinary L-FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis

Author

Manuel Morales-Ruiz, Marta Carol, Wladimiro Jiménez, Octavi Bassegoda, Isabel Graupera, Ann T. Ma, Adrià Juanola, Salvatore Piano, Núria Fabrellas, Laia Escudé, Martina Pérez-Guasch, Elisa Pose, Pere Ginès, Marta Cervera, Cristina Solé, Gonzalo Crespo, Chiara Elia, Ferran Torres, Ana-Belén Rubio, Elsa Solà, Emma Avitabile, and Laura Napoleone

Subjects
Male, medicine.medical_specialty, Cirrhosis, Urinary system, Kaplan-Meier Estimate, Urine, Fatty Acid-Binding Proteins, Gastroenterology, Statistics, Nonparametric, L-FABP, Internal medicine, medicine, Risk of mortality, Humans, Nonparametric, Prospective Studies, Mortality, Acute tubular necrosis, Aged, Proportional Hazards Models, Univariate analysis, Hepatology, business.industry, Acute-On-Chronic Liver Failure, Liver, Organ Failure, Biomarkers, Female, Middle Aged, Multivariate Analysis, Prognosis, Statistics, medicine.disease, Cohort, Biomarker (medicine), lipids (amino acids, peptides, and proteins), business
Abstract

Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC.A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison.Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis.Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC.Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.

Published
2022

30. Ductular reaction promotes intrahepatic angiogenesis through Slit2–Roundabout 1 signaling

Author

Juan José Lozano, Pau Sancho-Bru, Javier Gallego, Delia Blaya, Mercedes Fernandez, Anna Moles, Albert Pol, Pere Ginès, Andrea Fernández-Vidal, Jian-Guo Geng, Julia Vallverdú, Teresa Rubio-Tomás, Ester Garcia-Pras, Ramon Bataller, Mar Coll, Beatriz Aguilar-Bravo, Elisa Pose, Celia Martínez-Sánchez, Isabel Graupera, Silvia Ariño, Instituto de Salud Carlos III, European Commission, National Institute on Alcohol Abuse and Alcoholism (US), Generalitat de Catalunya, European Foundation for Alcohol Research, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), and Ministerio de Educación, Cultura y Deporte (España)

Subjects
Alcoholic liver disease, Angiogenesis, Gene Expression, Neovascularization, Physiologic, Nerve Tissue Proteins, Vascular Remodeling, Chronic liver disease, Article, Mice, Downregulation and upregulation, Fibrosis, medicine, Animals, Humans, Receptors, Immunologic, Liver Diseases, Alcoholic, Liver injury, Tube formation, Wound Healing, Neovascularization, Pathologic, Hepatology, Hepatitis, Alcoholic, business.industry, Stem Cells, Patient Acuity, medicine.disease, Liver regeneration, Up-Regulation, Organoids, Gene Ontology, Liver, Chronic Disease, Disease Progression, Cancer research, Blood Vessels, Intercellular Signaling Peptides and Proteins, business, Signal Transduction
Abstract

Background and aims: Ductular reaction (DR) expands in chronic liver diseases and correlates with disease severity. Besides its potential role in liver regeneration, DR plays a role in the wound-healing response of the liver, promoting periductular fibrosis and inflammatory cell recruitment. However, there is no information regarding its role in intrahepatic angiogenesis. In the current study we investigated the potential contribution of DR cells to hepatic vascular remodeling during chronic liver disease. Approach and results: In mouse models of liver injury, DR cells express genes involved in angiogenesis. Among angiogenesis-related genes, the expression of Slit2 and its receptor Roundabout 1 (Robo1) was localized in DR cells and neoangiogenic vessels, respectively. The angiogenic role of the Slit2-Robo1 pathway in chronic liver disease was confirmed in ROBO1/2-/+ mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which displayed reduced intrahepatic neovascular density compared to wild-type mice. However, ROBO1/2 deficiency did not affect angiogenesis in partial hepatectomy. In patients with advanced alcohol-associated disease, angiogenesis was associated with DR, and up-regulation of SLIT2-ROBO1 correlated with DR and disease severity. In vitro, human liver-derived organoids produced SLIT2 and induced tube formation of endothelial cells. Conclusions: Overall, our data indicate that DR expansion promotes angiogenesis through the Slit2-Robo1 pathway and recognize DR cells as key players in the liver wound-healing response., Supported by grants from Fondo de Investigación Sanitaria Carlos III (FIS), cofinanced by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa” (FIS PI20/00765, PI17/00673, to P.S.-B; FIS 18-PI18/00862, to I.G and M.C); from the National Institute on Alcohol Abuse and Alcoholism (1U01AA026972-01 and AGAUR 2017-SGR-01456, to P.S.-B.); and from the European Foundation for Alcohol Research (EA1653, to P.S.-B.). M.C. is funded by the Ramon y Cajal program from the Ministerio de Ciencia e Innovación RYC2019-026662-I. P.G. is funded by the Agencia de Gestió d'Ajuts Universitaris i de Recerca 2014 SGR 708, Centro de Investigaciónen Red Enfermedades Hepáticas y Digestivas (CIBERehd), and Institució Catalana de Recerca i Estudis Avançats. S.A. received a grant from the Ministerio de Educación, Cultura y Deporte (FPU17/04992). B.A.-B. is funded by the Instituto de Salud Carlos III (FI16/00203)

Published
2021

31. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases

Author

Harry J. de Koning, Ivica Grgurević, Patrick S. Kamath, Laurent Castera, Emmanuel Tsochatzis, Frank Lammert, Isabel Graupera, Ann T. Ma, Núria Fabrellas, Dominique Roulot, Pere Ginès, Mª Alba Diaz, Salvador Augustin, Andrea Martini, Vincent Wai-Sun Wong, Judit Pich, Rosa Maria Morillas, Philip N. Newsome, Miquel Serra-Burriel, Maja Thiele, Aleksander Krag, Phillipp Hartmann, Robert J. de Knegt, Michael P Manns, Montserrat García-Retortillo, Jörn M. Schattenberg, Indra Neil Guha, Alina M. Allen, Llorenç Caballería, Institut Català de la Salut, [Ginès P, Graupera I] Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain. August Pi I Sunyer Biomedical Research Institute, Barcelona, Spain. Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain. Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Castera L] Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. Université de Paris, Paris, France. Inserm UMR 1149, Centre de Recherche Sur L'inflammation, Paris, France. [Lammert F] Department of Medicine II, Saarland University Medical Center, Homburg, Germany. Institute for Occupational Medicine and Public Health, Saarland University, Homburg, Germany. Health Sciences, Hannover Medical School, Hannover, Germany. [Serra-Burriel M] Epidemiology, Statistics, and Prevention Institute, University of Zurich, Zurich, Switzerland. [Allen AM] Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA. [Salvador A] Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain. Unitat Hepàtica, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrosi hepàtica - Diagnòstic, Cirrhosis, Fibrosi, Biopsy, enfermedades del sistema digestivo::enfermedades hepáticas::cirrosis hepática [ENFERMEDADES], Population, Digestive System Diseases::Liver Diseases::Liver Cirrhosis [DISEASES], Otros calificadores::/diagnóstico [Otros calificadores], Disease, Fetge -- Malalties, Diagnosis::Diagnostic Techniques and Procedures::Mass Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Asymptomatic, Gastroenterology, Global Burden of Disease, Liver disease, Hepatitis B, Chronic, SDG 3 - Good Health and Well-being, Liver Function Tests, Non-alcoholic Fatty Liver Disease, Risk Factors, Fibrosis, Internal medicine, Prevalence, Cribatge (Medicina), Other subheadings::/diagnosis [Other subheadings], diagnóstico::técnicas y procedimientos diagnósticos::cribado sistemático [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Humans, Mass Screening, Medicine, education, liver fibrosis, education.field_of_study, Hepatology, business.industry, Fatty liver, Cirrosi, Hepatitis C, Chronic, medicine.disease, Early Diagnosis, Liver, Disease Progression, Elasticity Imaging Techniques, medicine.symptom, Transient elastography, business
Abstract

Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression. LiverScreen Consortium and the European Commission under the H20/20 program (847989); AGAUR (2017SGR-01281); Centro de Investigacion Biomedica en Enfermedades Hepaticas y Digestivas; Fundación de Investigación Sanitaria, cofunded by Instituto Carlos III–Subdirección General de Evaluación and the European Regional Development Fund (PI18/01330, PI18/00662, and PI18/00862); and Gilead’s Investigator–sponsored research program (IN-ES-989-5309)

Published
2021

32. Screening for fibrosis to diagnose liver diseases early

Author

Pere Ginès, Maja Thiele, Isabel Graupera, Miquel Serra-Burriel, Robert J. de Knegt, Frank Lammert, Laurent Castera, Marko Korenjak, Patrick S. Kamath, Ivica Grgurević, Salvatore Piano, Núria Fabrellas, Anita Arslanow, Aleksander Krag, and Gastroenterology & Hepatology

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology
Published
2023

33. Sequential changes in urinary biomarker levels in patients with cirrhosis and severe hepatorenal syndrome

Author

Adrià Juanola, Octavi Bassegoda, Ana Belen Rubio, Elsa Solà, Ann T. Ma, Elisa Pose, Cristina Solé, Núria Fabrellas, Pere Ginès, Laura Napoleone, Patrick S. Kamath, Isabel Graupera, Manuel Morales-Ruiz, Marta Carol, Martina Perez, Emma Avitabile, Marta Cervera, and Jordi Gratacós-Ginès

Subjects
Liver Cirrhosis, medicine.medical_specialty, Hepatorenal Syndrome, Cirrhosis, medicine.medical_treatment, Urinary system, Liver transplantation, urologic and male genital diseases, Gastroenterology, Hepatorenal syndrome, Internal medicine, medicine, Humans, Acute tubular necrosis, Hepatology, urogenital system, business.industry, Acute kidney injury, Acute Kidney Injury, medicine.disease, female genital diseases and pregnancy complications, Liver Transplantation, Transplantation, Biomarker (medicine), business, Biomarkers
Abstract

Whether tubular injury develops in patients with acute kidney injury owing to hepatorenal syndrome (AKI-HRS) is controversial. We performed repeated measurements of biomarkers of tubular injury during a 14-day period in 60 patients with cirrhosis and AKI (34 with AKI-HRS meeting the classical definition of type 1 HRS and 26 with AKI owing to acute tubular necrosis, AKI-ATN). Nineteen of 34 patients had resolution of AKI-HRS, while the remainder had persistent AKI-HRS. The persistence of AKI-HRS was associated with remarkably high short-term mortality. There were no significant differences in urinary NGAL or IL-18 between patients with resolution vs those with persistent AKI-HRS throughout the 14-day period. By contrast, biomarker levels were significantly lower in AKI-HRS, even if persistent, compared to AKI-ATN. These findings are highly suggestive of lack of significant tubular injury in AKI-HRS and could be of value in the clinical decision between combined liver-kidney or liver transplantation alone in patients with cirrhosis and AKI candidates to transplantation.

Published
2021

34. Liver cirrhosis

Author

Pere Ginès, Aleksander Krag, Juan G Abraldes, Elsa Solà, Núria Fabrellas, and Patrick S Kamath

Subjects
Liver Cirrhosis, Risk Factors, Hypertension, Portal, Humans, General Medicine, Liver Failure
Abstract

Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.

Published
2021

36. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases

Author

Guadalupe Garcia-Tsao, W. Ray Kim, Scott W. Biggins, Florence Wong, Pere Ginès, Simon C. Ling, Mitra K. Nadim, and Paulo Angeli

Subjects
0301 basic medicine, medicine.medical_specialty, Hepatorenal Syndrome, Hepatology, business.industry, Gastroenterology, MEDLINE, Ascites, Peritonitis, medicine.disease, End Stage Liver Disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Spontaneous bacterial peritonitis, Hepatorenal syndrome, Internal medicine, Diagnosis evaluation, medicine, Humans, 030211 gastroenterology & hepatology, medicine.symptom, business
Published
2021

37. A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement

Author

Pere Ginès, Jordi Colmenero, Valeria Perez-Campuzano, Elisa Pose, Abiguei Torrents, Emma Avitabile, Gonzalo Crespo, Lluís Castells, Jordi Gratacós-Ginès, Jaume Tort, Enric Reverter, José Castellote, and Isabel Campos-Varela

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Cirrosi hepàtica, Cirrhosis, Multivariate analysis, Waiting Lists, medicine.medical_treatment, Trasplantament hepàtic, Liver transplantation, Antiviral Agents, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Cholestasis, Liver Cirrhosis, Alcoholic, Statistical significance, Internal medicine, medicine, Humans, Decompensation, Hepatology, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Liver Transplantation, 030104 developmental biology, Hepatic cirrhosis, Spain, Drinking of alcoholic beverages, Consum d'alcohol, Female, 030211 gastroenterology & hepatology, Hepatic transplantation, business
Abstract

Background & Aims To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). Methods We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. Results One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. Conclusions A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Lay summary Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

Published
2021

38. Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population‐based study

Author

Carmen Expósito, Núria Fabrellas, Pere Ginès, Elisa Pose, Llorenç Caballería, Pere Torán, Isabel Graupera, Alba Díaz, Guillem Pera, Jordi Gratacós-Ginès, Ana Belen Rubio, and Emma Avitabile

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Alcohol Drinking, Liver fibrosis, Population, Alcohol, Gastroenterology, 03 medical and health sciences, Liver disease, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, mental disorders, medicine, Humans, education, Metabolic Syndrome, education.field_of_study, Hepatology, medicine.diagnostic_test, business.industry, medicine.disease, Liver, chemistry, 030220 oncology & carcinogenesis, Liver biopsy, Cohort, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Transient elastography
Abstract

BACKGROUND AND AIMS Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Published
2021

39. Renal Replacement Therapy for Acute Kidney Injury in Severe Alcohol-Associated Hepatitis as a Bridge to Transplant or Recovery

Author

Vijay H. Shah, Douglas A. Simonetto, Pere Ginès, Nneka N. Ufere, Kristin C. Mara, Brian E. Jones, Patrick S. Kamath, Andrew S. Allegretti, Elisa Pose, and Emma Avitabile

Subjects
Hepatitis, medicine.medical_specialty, Physiology, business.industry, medicine.medical_treatment, Gastroenterology, Acute kidney injury, Alcoholic hepatitis, Hepatology, Liver transplantation, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Hepatorenal syndrome, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, Renal replacement therapy, business
Abstract

Acute kidney injury is seen in approximately 30% of patients with severe alcohol-associated hepatitis (AH) and is associated with increased mortality. Controversy exists surrounding initiation of renal replacement therapy (RRT) in these patients, as most are ineligible for early transplantation. The primary aim was to identify predictors of survival and identify patients who may benefit from RRT as a bridge to transplant or recovery. A retrospective multicenter cohort of adult patients with AH, who received RRT, was developed, including patients from two North American and one European liver transplant centers. Fifty-five patients were included. Survival was 26/55 (47.3%) at 30 days, 17/55 (30.9%) at 3 months, and 15/55 (27.2%) at 6 months. Of those who survived 6 months, 2/15 (13.3%) received simultaneous liver and kidney transplantation, 11/15 (73.3%) had spontaneous recovery of kidney function, and 2/15 (13.3%) remained on RRT. Of patients who survived at least 3 months, 8/17 (47%) completed addiction treatment. Predictors of mortality were pre-RRT MELD (OR 1.10, 1.02–1.19) and pre-RRT MELD-Na (OR 1.14, 1.03–1.27). Pre-RRT MELD-Na

Published
2021

40. Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure

Author

Carlo Alessandria, Carmine Gambino, Javier Fernández, Hans Van Vlierberghe, Sophie Restellini, Marcos Girala, Luis Colombato, Tae Hee Lee, Nikolaos Pyrsopoulos, Eduardo Fassio, Sang Gyune Kim, Gisela Pinero, Paolo Caraceni, Shivaram Prasad Singh, Do Seon Song, Ji Won Park, Julio Vorobioff, Dong Joon Kim, C. Toledo, Aleksander Krag, Liane Rabinowich, Preetam Nath, Robert A. de Man, Elza Cotrim Soares, Xavier Verhelst, Tiago Sevá Pereira, Gustavo Romero, Macarena Simón-Talero, Sung Eun Kim, Michele Bartoletti, Alexander L. Gerbes, Sebastián Marciano, Tony Bruns, Hyoung Su Kim, Ki Tae Suk, Nicolas M. Intagliata, Annette Dam Fialla, Adrià Juanola, Manuela Merli, Rita de Cassia Ribeiro Barea, Laure Elkrief, Rakhi Maiwall, Laurentius A Lesmana, Pere Ginès, Vikas Gautam, E.L. Yoon, M. Marino, Paolo Angeli, Kalyan Ram Bhamidimarri, Victor Vargas, Virendra Singh, Juan Pablo Roblero, François Durand, Cosmas A. Rinaldi Lesmana, M. V. Maevskaya, Gustavo Navarro, Adrian Gadano, Florence Wong, Pramod Kumar, Tae Hun Kim, Daniela Campion, Salvatore Piano, Giacomo Zaccherini, Barbara Lattanz, Jae Seok Hwang, Sun Young Yim, Thomas D. Boyer, Jeong Han Kim, Carlos Brodersen, Wong F., Piano S., Singh V., Bartoletti M., Maiwall R., Alessandria C., Fernandez J., Soares E.C., Kim D.J., Kim S.E., Marino M., Vorobioff J., Barea R.D.C.R., Merli M., Elkrief L., Vargas V., Krag A., Singh S.P., Lesmana L.A., Toledo C., Marciano S., Verhelst X., Intagliata N., Rabinowich L., Colombato L., Kim S.G., Gerbes A., Durand F., Roblero J.P., Bruns T., Yoon E.L., Girala M., Pyrsopoulos N.T., Kim T.H., Yim S.Y., Juanola A., Gadano A., Angeli P., Bhamidimarri K., Boyer T.D., Brodersen C., Campion D., Caraceni P., de Man R.A., Fassio E., Fialla A.D., Gambino C., Gautam V., Gines P., Hwang J.S., Kim H.S., Kim J.H., Kumar P., Lattanz B., Lee T.H., Rinaldi Lesmana C.A., Maevskaya M., Nath P., Navarro G., Park J.-W., Pinero G., Restellini S., Romero G., Seva -Pereira T., Simon-Talero M., Song D.S., Suk K.T., Van Vlierberghe H., and Zaccherini G.

Subjects
Male, 0301 basic medicine, Cirrhosis, Organ Dysfunction Scores, Antibiotic resistance, medicine.medical_treatment, Liver transplantation, Severity of Illness Index, 0302 clinical medicine, ACLF, MDR, Epidemiology, Cross Infection, Mortality rate, Age Factors, Bacterial Infections, Middle Aged, Prognosis, Community-Acquired Infections, Europe, Hospitalization, Female, 030211 gastroenterology & hepatology, Alcohol-Related Disorders, medicine.medical_specialty, Sepsi, India, Risk Assessment, Sepsis, 03 medical and health sciences, Sex Factors, Spontaneous bacterial peritonitis, Internal medicine, medicine, Humans, XDR, Cirrhosi, Hepatology, business.industry, Acute-On-Chronic Liver Failure, medicine.disease, Pneumonia, 030104 developmental biology, antibiotic resistance, liver transplantation, sepsis, business
Abstract

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p

Published
2021

42. Clinical Application of Kidney Biomarkers in Cirrhosis

Author

Pere Ginès, Elsa Solà, and Andrew S. Allegretti

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, 030232 urology & nephrology, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, Liver disease, chemistry.chemical_compound, 0302 clinical medicine, Model for End-Stage Liver Disease, Hepatorenal syndrome, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Acute tubular necrosis, Creatinine, biology, urogenital system, business.industry, Acute kidney injury, Acute Kidney Injury, Prognosis, medicine.disease, female genital diseases and pregnancy complications, Cystatin C, chemistry, Nephrology, Disease Progression, biology.protein, business, Biomarkers, Glomerular Filtration Rate
Abstract

Acute kidney injury (AKI) is one of the most common and morbid complications of decompensated cirrhosis. Management of AKI is dictated by cause: prerenal AKI is treated with volume resuscitation; hepatorenal syndrome (HRS), with intravenous albumin and vasoconstrictors; and acute tubular necrosis, with supportive care. However, differentiating between causes is difficult using creatinine-based definitions of AKI alone. The use of novel kidney biomarkers in AKI and cirrhosis provides an opportunity to improve both the diagnosis and prognosis of this vulnerable population. This review examines the challenges of AKI in cirrhosis and the research experience around novel kidney biomarkers in cirrhosis. Specific focus is paid to the tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL), which has been the most studied in liver disease and has demonstrated the strongest performance in differentiating the cause of AKI (acute tubular necrosis vs functional injury such as prerenal AKI or HRS), as well as improving the prognostic performance of mortality prediction models such as the model for end stage liver disease (MELD) score. We advocate for the discussion of incorporating markers such as NGAL in the next iteration of HRS guidelines and identify areas for future research in this clinical condition.

Published
2020

43. Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension

Author

Pau Sancho-Bru, Rajanikanth Vadigepalli, Bin Gao, Ramon Bataller, Yan Cai, Shizuo Akira, Juan Caballería, Pere Ginès, Natasha T. Snider, Joaquín Cabezas, Jiegen Chen, Veronica Massey, Ivan Rusyn, Josepmaria Argemi, José Altamirano, Mingjiang Xu, Austin Parrish, and Gemma Odena

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, lcsh:Medicine, Lipocalin, Mice, 0302 clinical medicine, Fibrosis, Portal hypertension, lcsh:Science, Carbon Tetrachloride, TIMP1, Mice, Knockout, Liver injury, Multidisciplinary, Malalties del fetge, Liver, Female, 030211 gastroenterology & hepatology, medicine.medical_specialty, Liver fibrosis, Alcoholic hepatitis, Hipertensió portal, Peripheral blood mononuclear cell, Article, Collagen Type I, 03 medical and health sciences, Lipocalin-2, Downregulation and upregulation, Internal medicine, Hypertension, Portal, medicine, Animals, Humans, Liver diseases, Tissue Inhibitor of Metalloproteinase-1, Ethanol, Hepatitis, Alcoholic, business.industry, lcsh:R, Alcoholic liver disease, Microarray Analysis, medicine.disease, Collagen Type I, alpha 1 Chain, Disease Models, Animal, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Hepatocytes, lcsh:Q, business
Abstract

Advanced fibrosis and portal hypertension influence short-term mortality. Lipocalin 2 (LCN2) regulates infection response and increases in liver injury. We explored the role of intrahepatic LCN2 in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic LCN2 expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers, LCN2 expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2−/− mice were protected from liver fibrosis caused by either ethanol or CCl4 exposure. Microarray analysis revealed downregulation of matrisome, cell cycle and immune related gene sets in Lcn2−/− mice exposed to CCl4, along with decrease in Timp1 and Edn1 expression. Hepatic expression of COL1A1, TIMP1 and key EDN1 system components were elevated in AH patients and correlated with hepatic LCN2 expression. In vitro, recombinant LCN2 induced COL1A1 expression. Overexpression of LCN2 increased HIF1A that in turn mediated EDN1 upregulation. LCN2 contributes to liver fibrosis and portal hypertension in AH and could represent a new therapeutic target.

Published
2020

44. Development of chronic kidney disease after acute kidney injury in patients with cirrhosis is common and impairs clinical outcomes

Author

Cristina Solé, P. Huelin, Isabel Graupera, Elisa Pose, Javier Fernández, Marta Cervera, Jordi Gratacós-Ginès, Núria Fabrellas, Marta Carol, Pere Ginès, Laura Napoleone, Gloria de Prada, Octavi Bassegoda, Xavier Ariza, Sonia Albertos, Adrià Juanola, Elsa Solà, and Esteban Poch

Subjects
0301 basic medicine, medicine.medical_specialty, Cirrhosis, Hepatology, urogenital system, business.industry, medicine.medical_treatment, Acute kidney injury, Renal function, Odds ratio, Liver transplantation, urologic and male genital diseases, Chronic liver disease, medicine.disease, female genital diseases and pregnancy complications, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Hepatorenal syndrome, Internal medicine, Medicine, 030211 gastroenterology & hepatology, business, Kidney disease
Abstract

Background & Aims Acute kidney injury (AKI) is common in cirrhosis and is associated with poor prognosis. In patients who survive after AKI, it is not known whether the acute injury leads to chronic impairment of kidney function (chronic kidney disease [CKD]). The aim of the study was to determine the frequency of CKD at 3 months after an AKI episode and its effects on patient outcomes. Methods Patients admitted for complications of cirrhosis during a 6.5-year period were evaluated using the same protocol, with assessment of kidney function at regular intervals during and after hospitalization. CKD was defined as estimated glomerular filtration rate (eGFR) Results A total of 409 patients (168 with AKI and 241 without AKI) were included. After 3 months, 97 patients with AKI and 188 patients without AKI had survived. Of the 97 patients with AKI, 24 had developed CKD at 3 months compared to only 2 of the 188 patients without AKI (25% vs. 1%, odds ratio 31; p Conclusions CKD frequently develops in patients with cirrhosis who survive AKI and has a negative impact on relevant clinical outcomes. The transition from AKI to CKD is common and should be considered a high-risk condition in patients with cirrhosis. Lay summary Episodes of acute impairment of kidney function are common in patients with cirrhosis. This study shows that the development of chronic impairment of kidney function is frequent in patients surviving these acute episodes and that it is associated with a higher risk of developing other complications of cirrhosis and to a higher rate of 3-month hospital readmissions.

Published
2020

45. Hospital-Acquired Versus Community-Acquired Acute Kidney Injury in Patients With Cirrhosis: A Prospective Study

Author

Archita P. Desai, Hani Shamseddeen, Pere Ginès, Chenjia Xu, Kavish R. Patidar, Lauren Nephew, Eric S. Orman, Marwan Ghabril, Tarek M. El-Achkar, Naga Chalasani, and Melissa Anderson

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, urologic and male genital diseases, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, Hospital Mortality, Prospective Studies, Renal Insufficiency, Chronic, Prospective cohort study, Aged, Hepatology, urogenital system, business.industry, Proportional hazards model, Hazard ratio, Gastroenterology, Acute kidney injury, Odds ratio, Acute Kidney Injury, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Confidence interval, Survival Rate, 030220 oncology & carcinogenesis, Disease Progression, Female, 030211 gastroenterology & hepatology, business, Kidney disease
Abstract

OBJECTIVES: In patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI and community-acquired AKI in a large, prospective study. METHODS: Hospitalized patients with cirrhosis were enrolled (N=519) and were followed for 90 days following discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were development of de-novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regression were used to determine the independent association of either AKI for primary and secondary outcomes, respectively. RESULTS: Hospital-acquired AKI occurred in 10% and community-acquired AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with community-acquired AKI had a higher risk for mortality [adjusting for MELD-Na: hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.04–2.57), p=0.033; adjusting for ACLF: HR 2.44, 95%CI 1.63–3.65, p

Published
2020

46. The EASL–Lancet Liver Commission:protecting the next generation of Europeans against liver disease complications and premature mortality

Author

Tom H Karlsen, Nick Sheron, Shira Zelber-Sagi, Patrizia Carrieri, Geoffrey Dusheiko, Elisabetta Bugianesi, Rachel Pryke, Sharon J Hutchinson, Bruno Sangro, Natasha K Martin, Michele Cecchini, Mae Ashworth Dirac, Annalisa Belloni, Miquel Serra-Burriel, Cyriel Y Ponsioen, Brittney Sheena, Alienor Lerouge, Marion Devaux, Nick Scott, Margaret Hellard, Henkjan J Verkade, Ekkehard Sturm, Giulio Marchesini, Hannele Yki-Järvinen, Chris D Byrne, Giovanni Targher, Aviad Tur-Sinai, Damon Barrett, Michael Ninburg, Tatjana Reic, Alison Taylor, Tim Rhodes, Carla Treloar, Claus Petersen, Christoph Schramm, Robert Flisiak, Marieta Y Simonova, Albert Pares, Philip Johnson, Alessandro Cucchetti, Isabel Graupera, Christos Lionis, Elisa Pose, Núria Fabrellas, Ann T Ma, Juan M Mendive, Vincenzo Mazzaferro, Harry Rutter, Helena Cortez-Pinto, Deirdre Kelly, Robyn Burton, Jeffrey V Lazarus, Pere Ginès, Maria Buti, Philip N Newsome, Patrizia Burra, Michael P Manns, Karlsen T.H., Sheron N., Zelber-Sagi S., Carrieri P., Dusheiko G., Bugianesi E., Pryke R., Hutchinson S.J., Sangro B., Martin N.K., Cecchini M., Dirac M.A., Belloni A., Serra-Burriel M., Ponsioen C.Y., Sheena B., Lerouge A., Devaux M., Scott N., Hellard M., Verkade H.J., Sturm E., Marchesini G., Yki-Jarvinen H., Byrne C.D., Targher G., Tur-Sinai A., Barrett D., Ninburg M., Reic T., Taylor A., Rhodes T., Treloar C., Petersen C., Schramm C., Flisiak R., Simonova M.Y., Pares A., Johnson P., Cucchetti A., Graupera I., Lionis C., Pose E., Fabrellas N., Ma A.T., Mendive J.M., Mazzaferro V., Rutter H., Cortez-Pinto H., Kelly D., Burton R., Lazarus J.V., Gines P., Buti M., Newsome P.N., Burra P., Manns M.P., Repositório da Universidade de Lisboa, University of Oslo (UiO), King‘s College London, Tel Aviv Sourasky Medical Center [Te Aviv], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), University College of London [London] (UCL), Università degli studi di Torino = University of Turin (UNITO), Bewdley Medical Centre [Bewdley, UK] (BMC), Glasgow Caledonian University (GCU), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, University of Bristol [Bristol], Organisation de Coopération et de Développement Economiques = Organisation for Economic Co-operation and Development (OCDE), University of Washington [Seattle], Public Health England [London], Universität Zürich [Zürich] = University of Zurich (UZH), Amsterdam UMC - Amsterdam University Medical Center, Burnet Institute [Melbourne, Victoria], Royal Prince Alfred Hospital [Sydney, Australia], University of Melbourne, University of Groningen [Groningen], University Children's Hospital of Tübingen, Partenaires INRAE, University hospital - Policlinico S.Orsola-Malpighi [Bologna, Italy], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University Hospital Southampton NHS Foundation Trust, Università degli studi di Verona = University of Verona (UNIVR), Max Stern Yezreel Valley college (YVC), University of Gothenburg (GU), World Hepatitis Alliance [London, UK] (WHA), European Liver Patients Organization [Brussels, Belgium] (ELPO), Croatian Society for Liver Diseases-Hepatos [Split, Croatia] (CSLDH), Children's Liver Disease Foundation [Birmingham, UK] (CLDF), London School of Hygiene and Tropical Medicine (LSHTM), University of New South Wales [Sydney] (UNSW), Hannover Medical School [Hannover] (MHH), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Medical University of Białystok (MUB), Medical Military Academy [Sofia, Bulgaria] (2MA), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Liverpool, University of Bologna/Università di Bologna, University of Crete [Heraklion] (UOC), University of Barcelona, Institute of Health Carlos III, Università degli Studi di Milano = University of Milan (UNIMI), University of Bath [Bath], Universidade de Lisboa = University of Lisbon (ULISBOA), University of Birmingham [Birmingham], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Instituto de Salud Carlos III [Madrid] (ISC), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), and Malbec, Odile

Subjects
Medicine(all), Mortality, Premature, [SDV]Life Sciences [q-bio], Liver Diseases, Health Policy, Liver Disease, Alcoholic liver diseases, General Medicine, Lancet commission, [SDV] Life Sciences [q-bio], Europe, SDG 3 - Good Health and Well-being, NAFLD, Liver diseases, NAFLD, Alcoholic liver diseases, Liver hepatitis, Lancet commission, Humans, Liver hepatitis, ComputingMilieux_MISCELLANEOUS, Human
Abstract

© 2021 Elsevier Ltd. All rights reserved., Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally., The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193; COMPARE: CIT5-CT-2005-028857; SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909; SHARE-LEAP: GA N°227822; SHARE M4: GA N°261982; DASISH: GA N°283646), and Horizon 2020 (SHARE-DEV3: GA N°676536; SHARE-COHESION: GA N°870628; SERISS: GA N°654221; SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2; P01_AG005842; P01_AG08291; P30_AG12815; R21_AG025169; Y1-AG-4553-01; IAG_BSR06-11; OGHA_04-064; HHSN271201300071C), and from various national funding sources is gratefully acknowledged. PC acknowledges support by the French National Agency for HIV, hepatitis and emerging infectious diseases research (ANRS / EMERGING INFECTIOUS DISEASES).

Published
2022

47. Global multi-stakeholder endorsement of the MAFLD definition

Author

Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. Lee, Way Seah Lee, Yeong Yeh Lee, Diana Julie Leeming, Nathalie Carvalho Leite, Roberto Leon, Cosmas Rinaldi Adithya Lesmana, Junfeng Li, Qiong Li, Jun Li, Yang-Yang Li, Yufang Li, Lei Li, Min Li, Yiling li, Huiqing Liang, Tang Lijuan, Seng Gee Lim, Lee-Ling Lim, Shumei Lin, Han-Chieh Lin, Rita Lin, Rania Lithy, Yaru Liu, Yuanyuan Liu, Xin Liu, Wen-Yue Liu, Shourong Liu, Ken Liu, Tian Liu, Amedeo Lonardo, Mariana Bravo López, Eva López-Benages, Patricio Lopez-Jaramillo, Huimin Lu, Lun Gen Lu, Yan Lu, John Lubel, Rashid Lui, Iulianna Lupasco, Elena Luzina, Xiao-Hui Lv, Kate Lynch, Hong-Lei Ma, Mariana Verdelho Machado, Nonso Maduka, Katerina Madzharova, Russellini Magdaong, Sanjiv Mahadeva, Amel Mahfouz, Nik Ritza Kosai Nik Mahmood, Eman Mahmoud, Mohamed Mahrous, Rakhi Maiwall, Ammar Majeed, Avik Majumdar, Loey Mak, Madiha M Maklouf, Reza Malekzadeh, Claudia Mandato, Alessandra Mangia, Jake Mann, Hala Hussien Mansour, Abdellah Mansouri, Alessandro Mantovani, Jun qian Mao, Flor Maramag, Giulio Marchesini, Claude Marcus, Rui António Rocha Tato Marinho, Maria L Martinez-Chantar, Antonieta A. 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Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease

Subjects
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract

Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)

Published
2022

48. Enfermedad hepática por alcohol. Guías de práctica clínica. Documento de consenso auspiciado por la AEEH

Author

Moisés Diago, Manuel Hernández-Guerra, Agustín Albillos, Rafael Bañares, Esther Molina, María Teresa Arias-Loste, Pere Ginès, Manuel Romero-Gómez, María Jesús Pareja, Joaquín Cabezas, Anna Lligoña, Santiago Tomé, Rocío Gallego, Javier Abad, Joan Genescà, Ramon Bataller, Juan Caballería, Ramon Planas, Rocío Aller, Javier Salmerón, F. Jorquera, José A. Carrión, José Altamirano, Carmelo García-Monzón, Meritxell Ventura-Cots, Miren García-Cortés, Conrado M Fernández Rodríguez, and Llorenç Caballería

Subjects
medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Gastroenterology, Alcoholic hepatitis, Disease, medicine.disease, Chronic liver disease, Liver disease, Internal medicine, medicine, Prednisolone, Steatohepatitis, Intensive care medicine, business, medicine.drug
Abstract

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

Published
2019

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