Liquid diagnosis of hepatic encephalopathy : are we there already?

© 2020 Sociedade Portuguesa de Gastrenterologia Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any dis-tribution of modified material requires written permission.Hepatic encephalopathy (HE) is a neurocognitive syndrome associated with liver disease and/or portosystemic shunts. Its diagnosis is clinical and requires exclusion of many other conditions that can present with similar neuropsychiatric abnormalities. The broad differential diagnosis, and huge clinical overlap with many metabolic, neurologic and psychiatric disorders, is a challenge for clinicians that must decide in which patients further laboratorial, imaging and neurophysiological investigation is warranted.info:eu-repo/semantics/publishedVersio

O crescente panorama do carcinoma hepatocelular associado ao fígado gordo não alcoólico e o seu impacto no rastreio

© 2023 The Author(s). Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution- NonCommercial 4.0 International License (CC BY-NC) (http://www. karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes require written permission.Liver cancer is globally the third leading cause of death from cancer. Hepatocellular carcinoma (HCC) develops in patients with underlying liver disease. The fraction of HCC attributed to nonalcoholic fatty liver disease (NAFLD) shows an accelerated increase in the last decades, being already responsible for 15% of all HCC cases. Similar to other causes of liver cirrhosis, patients with NAFLD-associated cirrhosis should be enrolled in HCC-screening programs, yet these patients are under-screened, and currently are less than half likely to be proposed for HCC screening as compared to patients with HCV-associated cirrhosis. NAFLD-associated HCC has the peculiarity of occurring in precirrhotic phases in 20-50% of the cases. Currently, HCC screening in precirrhotic NAFLD patients is not routinely recommended, since the risk of developing HCC is very low. However, because NAFLD affects one-third of the worldwide population, noncirrhotic NAFLD already accounts for 6% of HCC cases. As such, it is pressing to develop stratification tools, in order to personalize the individual risk of HCC development in a patient with NAFLD, allowing precision HCC-screening programs. This review summarizes the epidemiology of NAFLD-associated HCC with a critical analysis of current HCC-screening recommendations.O cancro do fígado é, globalmente, a terceira causa de morte por cancro. O carcinoma hepatocelular (CHC) desenvolve-se em doentes com doença hepática crónica subjacente. A fracção de CHC atribuível ao fígado gordo não alcoólico (FGNA) tem vindo a aumentar com uma aceleração no seu crescimento nas últimas décadas, sendo atualmente responsável por 15% dos casos de CHC. À semelhança do que ocorre com outras causas de cirrose hepática, os doentes com cirrose associada a FGNA devem ser inseridos em programas de rastreio de CHC. Contudo, esses doentes são sub-rastreados, já que a probabilidade de serem incluídos em programas de rastreio de CHC é menos de metade comparando com doentes com cirrose associada a hepatite C crónica. O CHC associado ao FGNA tem a particularidade de ocorrer em fases pré-cirróticas em 20 a 50% dos casos. O rastreio de CHC em doentes com FGNA em fase pré-cirrótica não está recomendado por rotina, uma vez que, ainda assim, o risco destes doentes desenvolverem CHC é muito baixo. No entanto, uma vez que um terço da população mundial tem FGNA, o FGNA em não cirróticos corresponde a 6% de todos os casos de CHC. Assim sendo, é urgente o desenvolvimento de métodos de estratificação, por forma a personalizar o risco individual de desenvolvimento de CHC em doentes com FGNA, permitindo maior precisão nos programas de rastreio de CHC. Esta revisão sumariza a epidemiologia de CHC associado ao FGNA, com uma análise crítica das atuais recomendações de rastreio de CHC.info:eu-repo/semantics/publishedVersio

MASLD treatment : a shift in the paradigm is imminent

© 2023 Machado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termsMASLD prevalence is growing towards the leading cause of end-stage liver disease. Up to today, the most effective treatment is weight loss. Weight loss interventions are moving from lifestyle changes to bariatric surgery or endoscopy, and, more recently, to a new wave of anti-obesity drugs that can compete with bariatric surgery. Liver-targeted therapy is a necessity for those patients who already present liver fibrosis. The field is moving fast, and in the near future, we will testify to a disruptive change in MASLD treatment, similar to the paradigm-shift that occurred for hepatitis C almost one decade ago with direct antiviral agents.info:eu-repo/semantics/publishedVersio

Aerobic exercise in the management of metabolic dysfunction associated fatty liver disease

© 2021 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Sedentarism is the pandemic of modern times. It is associated with several medical conditions including obesity, type 2 diabetes mellitus, cardiovascular diseases and also liver disease, particularly metabolic dysfunction associated fatty liver disease (MAFLD). In an era when MAFLD is the most prevalent chronic liver disease worldwide, whilst no pharmacological therapy has been approved for it, exercise has proved to be effective in improving liver steatosis. Interestingly, exercise decreases liver fat even in the absence of weight loss. The challenge for the clinician is to motivate the obese patient with MAFLD, and associated co-morbidities, who has crystallized a sedentary behavior, at times when every need is at the distance of a click on the Internet, and the entire world can be visited behind a screen. In this review, the aggregate evidence on the mechanisms and effects of exercise in the management of MAFLD is summarized, with simple recommendations for everyday clinical practice.info:eu-repo/semantics/publishedVersio

Benign inheritable disorders of bilirubin metabolism manifested by conjugated hyperbilirubinemia: a narrative review

© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. Hyperbilirubinemia is an important clinical sign that needs to be investigated under a stepwise evaluation. Inherited non-hemolytic conjugated hyperbilirubinemic conditions include Dubin-Johnson syndrome (caused by mutations affecting ABCC2 gene) and Rotor syndrome (caused by the simultaneous presence of mutations in SLCO1B1 and SLCO1B3 genes). Although classically viewed as benign conditions requiring no treatment, they lately gained an increased interest since recent studies suggested that mutations in the responsible genes leading to hyperbilirubinemia, as well as minor genetic variants, may result in an increased susceptibility to drug toxicity. This article provides a comprehensive review on the pathophysiology of Dubin-Johnson and Rotor syndromes, presenting the current knowledge concerning the molecular details and basis of these conditions.info:eu-repo/semantics/publishedVersio

Aerobic Exercise in the Management of Metabolic Dysfunction Associated Fatty Liver Disease

Sedentarism is the pandemic of modern times. It is associated with several medical conditions including obesity, type 2 diabetes mellitus, cardiovascular diseases and also liver disease, particularly metabolic dysfunction associated fatty liver disease (MAFLD). In an era when MAFLD is the most prevalent chronic liver disease worldwide, whilst no pharmacological therapy has been approved for it, exercise has proved to be effective in improving liver steatosis. Interestingly, exercise decreases liver fat even in the absence of weight loss. The challenge for the clinician is to motivate the obese patient with MAFLD, and associated co-morbidities, who has crystallized a sedentary behavior, at times when every need is at the distance of a click on the Internet, and the entire world can be visited behind a screen. In this review, the aggregate evidence on the mechanisms and effects of exercise in the management of MAFLD is summarized, with simple recommendations for everyday clinical practice.info:eu-repo/semantics/publishedVersio

Project management and business analysis: an analysis of Cofidis Portugal

Project managers and business analysts are more and more critical in nowadays’ companies. This dissertation explores the role of the business analyst and project manager at Cofidis Portugal, aiming at three main goals: to find out whether these roles are clear for the project team; to understand how the PM-BA/BA-PM relationship is perceived, and; to outline opportunity measures for both project management and business analysis. More than understanding the how project managers and business analysts perceive each other’s roles, this research intends to show a 360º overview of the roles of project manager and business analyst. This means that the perspective of the reality shown in this research is not only from the project manager’s or business analyst’s point of view, but from all project stakeholders’ point of view. To reach this goal, 57 answers from project team members from different areas at Cofidis Portugal were analyzed. The findings show that project team members are generally aware of project management and business analysis tasks. However, the respondents find overlapping tasks between both areas. Although they define the PM-BA/BA-PM relationship as neutral, they also agree on the fact that there is room for improvement. As for improvement measures, three are suggested: fostering a PM-BA/BA-PM partnership, implementing a dynamic team and improve business knowledge.Gestores de projeto e analistas funcionais são cada vez mais importantes nas empresas de hoje em dia. Esta dissertação explora a função de Analista Funcional e Gestor de Projeto na Cofidis Portugal. Esta investigação tem três objetivos: perceber se estas funções estão claras para a equipa de projeto; entender como a relação entre Gestor de Projeto e Analista Funcional/Analista Funcional – Gestor de Projeto é percecionada; e delinear os eixos de melhoria para a Gestão de Projeto e Análise Funcional. Mais do que perceber como o gestor de projeto e analista funcional percecionam as funções de cada um, esta pesquisa visa mostrar uma análise 360º sobre a função de gestor de projeto e de analista funcional. Isto significa que a perspetiva da realidade mostrada nesta pesquisa não é apenas do ponto de vista de um gestor de projeto ou analista funcional, mas sim do ponto de vista de todos os stakeholders de projeto. De forma a atingir este objetivo, 57 respostas provenientes de membros das equipas de projeto de várias áreas na Cofidis Portugal foram analisadas. Os resultados indicam que os membros da equipa de projeto têm a noção das tarefas de gestão de projeto e análise funcional. Não obstante, os inquiridos encontram tarefas sobrepostas entre as duas áreas. Apesar destes definirem a relação gestor de projetoanalista funcional/analista funcional – gestor de projeto como neutra, também concordam com o facto que existe espaço para melhorias. Em relação a sugestões de melhoria, três são sugeridas: fomentar uma parceria entre o gestor de projeto-analista funcional/analista funcional – gestor de projeto, implementar uma equipa dinâmica e melhorar o conhecimento do negócio

What is the role of caspase-2 mediated lipoapoptosis in the pathogenesis of the metabolic syndrome-associated liver disease, nonalcoholic fatty liver disease (NAFLD)?

Nonalcoholic fatty liver disease can be considered the hepatic manifestation of obesity and the metabolic syndrome. It is the number one cause of chronic liver disease in the Western world. Lipotoxicity in the liver induces epithelial lesion that triggers a wound healing response. In susceptible subjects the wound healing response is ineffective in repairing and regenerating the injured liver, leading to scarring, fibrogenesis and eventually hepatic cirrhosis. Though important advances in the knowledge of the pathogenesis of NAFLD have occurred since its firsts descriptions in 1980, gaps in knowledge still precludes Hepatologists to find an effective treatment for this pandemic. We first extensively characterized and compared two dietary mouse models of NAFLD, methionine-choline deficient (MCD) and Western diets. We found that MCD diet induces severe disease with significant fibrosis, whereas Western diet induces mild disease, but associates with obesity, insulin resistance and the metabolic syndrome. Afterwards, we demonstrated a pivotal role of caspase-2 in the development of the metabolic syndrome, NAFLD, progression to severe liver disease and hepatic fibrogenesis. Caspase-2 was up-regulated in human NAFLD and in in several different mouse models of NAFLD, correlating with the degree of fibrosis. Also, caspase-2 deficient mice were protected from the metabolic syndrome and liver injury/fibrosis in both MCD and Western diet mouse models. Finally, we found that in different mouse models of NAFLD, hepatic free coenzyme A content is decreased, which could potentiate caspase-2 activation. We conducted a preclinical trial in mice submitted to MCD diet, treating them with coenzyme A precursors. This approach failed to correct hepatic free coenzyme A levels and had no impact in liver histology or caspase-2 expression/activation. Our work places caspase-2 as a potential therapeutic target for obesity-associated diseases, such as type 2 diabetes mellitus and NAFLD.Fundação Calouste GulbenkianFundação CampalimaudMinistério da saúdeFundação para a Ciência e Tecnologi

Rotor Syndrome Presenting as Dubin-Johnson Syndrome

A 42-year-old man with no relevant past medical history presented with intermittent mild icterus and no signs of chronic liver disease. Laboratory tests were notable for hyperbilirubinemia (total 7.97 mg/dL, direct 5.37 mg/dL), bilirubinuria, no signs of hemolysis, normal liver tests and lipids profile. Abdominal ultrasound was unremarkable. A panel of chronic liver diseases was negative except for increased serum (147.4 μg/dL) and urinary (179 μg/24 h) copper, with normal ceruloplasmin. No other Leipzig criteria for Wilson’s disease were found, including a negative test for ATP7B gene mutations (by exome sequencing). Total urinary coproporphyrin was normal with predominance of isomer I (86% of total urinary coproporphyrin output). Clinical and laboratorial profile was compatible with Dubin-Johnson syndrome; however, exome sequencing and search for deletions in the ABBC2 gene (encoding MRP2) only found a heterozygous potentially pathogenic variant (c.1483A>G – p.Lys495Glu). Additional extended molecular analysis of genes implicated in bilirubin metabolism found a homozygous deletion of a region encompassing exons 4–16 of SLCO1B3 gene (encoding OATP1B3) and all SLCO1B1 exons (encoding OATP1B1), thereby establishing Rotor syndrome diagnosis. Rotor and DubinJohnson syndromes are rare autosomal recessive liver diseases characterized by chronic conjugated hyperbilirubinemia, caused by the absence of the hepatic function OATP1B1/B3 (leading to impaired hepatic bilirubin reuptake and storage) and MRP2 transporters (leading to impaired hepatic bilirubin excretion), respectively. We report a case of compound hereditary hyperbilirubinemia with a misleading presentation with special focus on its diagnosis, particularly the advantage of extensive unbiased genetic testing by dedicated laboratories. With this case, we aim to highlight the necessity of establishing a diagnosis, reassuring the patient, and avoiding unnecessary invasive and costly diagnostic procedures.info:eu-repo/semantics/publishedVersio

Conflito e Triangulação Coparental, Regulação Emocional e Problemas Externalizantes em Adolescentes: Relações diretas e indiretas

Las dificultades en la coparentalidad reverberan en problemas de externalización en adolescentes. Sin embargo, existe una falta de comprensión sobre los mecanismos que median esta relación. La regulación emocional es un posible vínculo entre estos constructos. El objetivo de este estudio fue probar un modelo estructural en el que la desregulación emocional es mediadora entre la coparentalidad y los problemas de externalización en adolescentes. Este es un estudio cuantitativo, transversal y explicativo. Cuenta con una muestra de 229 adolescentes entre 11 y 18 años que viven en el interior de Rio Grande do Sul. Se utilizó el modelo de ecuaciones estructurales para probar la validez empírica del modelo teórico propuesto. Los resultados proporcionaron evidencia para el avance del estudio de las relaciones familiares y los mecanismos explicativos en el desarrollo de problemas de externalización. Algunos dominios de desregulación emocional median la asociación entre las dimensiones negativas de los problemas de coparentalidad y problemas de externalización. Se analizan y discuten las relaciones directas e indirectas entre las variables del modelo.Dificuldades no exercício da coparentalidade reverberam em problemas externalizantes em adolescentes. Entretanto, há escassez no entendimento sobre mecanismos que medeiam essa relação. A regulação emocional apresenta-se como possível ligação entre esses construtos. O objetivo deste estudo foi testar um modelo estrutural no qual a desregulação emocional é mediadora entre coparentalidade e problemas externalizantes em adolescentes. Trata-se de estudo com delineamento quantitativo, transversal, explicativo. Contou com uma amostra de 229 adolescentes entre 11 a 18 anos, residentes no interior do Rio Grande do Sul. Foi utilizada modelagem de equações estruturais para testar a validade empírica do modelo teórico proposto. Os resultados forneceram evidências para o avanço do estudo das relações familiares e mecanismos explicativos no desenvolvimento de problemas externalizantes. Alguns domínios de desregulação emocional são mediadores da associação entre dimensões negativas de coparentalidade e problemas externalizantes. As relações diretas e indiretas entre as variáveis do modelo são analisadas e discutidas.Difficulties in coparenting performance reverberate in externalizing problems in adolescents. However, understanding on the mechanisms mediating this relationship is scarce. Emotion regulation is a possible link between these constructs. This study aims to test a structural model in which emotional dysregulation mediates coparenting and externalizing problems in adolescents. This is a quantitative, cross-sectional, and explanatory study. The sample consisted of 229 adolescents aged between 11 and 18, living in inland cities of Rio Grande do Sul. Structural equation modeling was used to test the empirical validity of the proposed theoretical model. Results provided evidence for the advance of the study on family relationships and explanatory mechanisms in the development of externalizing problems. Some domains of emotion deregulation mediate the association between coparenting negative dimensions and externalizing problems. Direct and indirect relationships between the model variables are analyzed and discussed