Gut mycobiota changes in liver diseases: A systematic review.

Intestinal fungi play an important role in the health-disease process. We observed that in liver diseases, fungal infections lead to high mortality. In this review, we were able to gather and evaluate the available scientific evidence on intestinal mycobiota and liver diseases. We searched PubMed and Embase, using a combination of several entry terms. Only studies in adults ≥ 18 years old with liver disease and published after 2010 were included. We observed that individuals with liver disease have an altered intestinal mycobioma, which accompanies the progression of these diseases. In cirrhotic patients, there are a high number of Candida sp. strains, especially Candida albicans. In early chronic liver disease, there is an increase in alpha diversity at the expense of Candida sp. and conversely, in advanced liver disease, there is a negative correlation between alpha diversity and model for end-stage liver disease score. On the other hand, patients with non-alcoholic fatty liver disease demonstrate greater diversity compared to controls. Our study concluded that the evidence on the subject is sparse, with few studies and a lack of standardization of outcome measures and reporting, and it was not possible to perform a meta-analysis capable of synthesizing relevant parameters of the human mycobiotic profile. However, certain fungal genera such as Candida play an important role in the context of liver disease and that adults with liver disease have a distinct gut mycobiotic profile from healthy controls.

In people with end-stage liver disease, there is a high mortality from fungal infections. In this context, the genus Candida plays an important role in the context of liver disease, and adults with liver disease have a distinct gut mycobiota profile from healthy controls.

Update on Biologic Therapies for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease driven by genetic, hormonal, and environmental factors. Despite the advances in diagnostic and therapeutic approaches in the last decades, SLE still leads to significant morbidity and increased mortality. Although a cure for SLE is still unknown, treatment is required to control acute disease exacerbation episodes (flares), decrease the frequency and severity of subsequent lupus flares, address comorbidities, and prevent end-organ damage. While conventional SLE pharmacotherapy may exhibit suboptimal efficacy and substantial toxicity, a growing knowledge of the disease pathogenesis enabled the research on novel therapeutic agents directed at specific disease-related targets. In this paper, we review the recent progress in the clinical investigation of biologic agents targeting B cells, T cells, cytokines, innate immunity, and other immunologic or inflammatory pathways. Although many investigational agents exhibited insufficient efficacy or inadequate safety in clinical trials, one of them, belimumab, fulfilled the efficacy and safety regulatory requirements and was approved for the treatment of SLE in Europe and the USA, which confirms that, despite all difficulties, advances in this field are possible.

COMPARISON OF GUT MICROBIOTA IN ALCOHOLIC AND METABOLIC-DYSFUNCION ASSOCIATED STEATOTIC LIVER DISEASE IN ANIMAL MODELS.

BACKGROUND: Alcoholic liver disease (ALD) and metabolic-dysfunction associated steatotic liver disease (MASLD) are common, and gut microbiota (GM) is involved with both. Here we compared GM composition in animal models of MASLD and ALD to assess whether there are specific patterns for each disease. METHODS: MASLD model- adult male Sprague Dawley rats, randomized into two groups: MASLD-control (n=10) fed a standard diet; MASLD-group (n=10) fed a high-fat-choline-deficient diet for 16 weeks. ALD model- adult male Wistar rats randomized: ALD-control (n=8) fed a standard diet and water+0.05% saccharin, ALD groups fed with sunflower seed and 10% ethanol+0.05% saccharin for 4 or 8 weeks (ALC4, n=8; ALC8, n=8). ALC4/8 on the last day received alcoholic binge (5g/kg of ethanol). Afterwards, animals were euthanized, and feces were collected for GM analysis. RESULTS: Both experimental models induced typical histopathological features of the diseases. Alpha diversity was lower in MASLD compared with ALD (p<0.001), and structural pattern was different between them (P<0.001). Bacteroidetes (55.7%), Firmicutes (40.6%), and Proteobacteria (1.4%) were the most prevalent phyla in all samples, although differentially abundant among groups. ALC8 had a greater abundance of the phyla Cyanobacteria (5.3%) and Verrucomicrobiota (3.2%) in relation to the others. Differential abundance analysis identified Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136_group, and Turicibacter associated with ALC4 and the Clostridia_UCG_014_ge and Gastranaerophilales_ge genera to ALC8. CONCLUSION: In this study, we demonstrated that the structural pattern of the GM differs significantly between MASLD and ALD models. Studies are needed to characterize the microbiota and metabolome in both clinical conditions to find new therapeutic strategies. BACKGROUND: •Changes in the composition of the intestinal microbiota are related to the development of alcoholic liver disease and metabolic-dysfunction associated steatotic liver disease. BACKGROUND: •The diversity of the intestinal microbiota was lower in animals with MASLD compared to ALD. BACKGROUND: •The structural pattern of the intestinal microbiota was significantly different among the experimental groups. BACKGROUND: •Studies are needed to characterize the composition of the intestinal microbiota and metabolome to find new therapeutic strategies.

Comparação da microbiota intestinal em modelos animais de doença hepática esteatótica alcoólica e metabólica / Comparison of gut microbiota in alcoholic and metabolic-dysfuncion associated steatotic liver disease in animal models

ABSTRACT Background: Alcoholic liver disease (ALD) and metabolic-dysfunction associated steatotic liver disease (MASLD) are common, and gut microbiota (GM) is involved with both. Here we compared GM composition in animal models of MASLD and ALD to assess whether there are specific patterns for each disease. Methods: MASLD model- adult male Sprague Dawley rats, randomized into two groups: MASLD-control (n=10) fed a standard diet; MASLD-group (n=10) fed a high-fat-choline-deficient diet for 16 weeks. ALD model- adult male Wistar rats randomized: ALD-control (n=8) fed a standard diet and water+0.05% saccharin, ALD groups fed with sunflower seed and 10% ethanol+0.05% saccharin for 4 or 8 weeks (ALC4, n=8; ALC8, n=8). ALC4/8 on the last day received alcoholic binge (5g/kg of ethanol). Afterwards, animals were euthanized, and feces were collected for GM analysis. Results: Both experimental models induced typical histopathological features of the diseases. Alpha diversity was lower in MASLD compared with ALD (p<0.001), and structural pattern was different between them (P<0.001). Bacteroidetes (55.7%), Firmicutes (40.6%), and Proteobacteria (1.4%) were the most prevalent phyla in all samples, although differentially abundant among groups. ALC8 had a greater abundance of the phyla Cyanobacteria (5.3%) and Verrucomicrobiota (3.2%) in relation to the others. Differential abundance analysis identified Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136_group, and Turicibacter associated with ALC4 and the Clostridia_UCG_014_ge and Gastranaerophilales_ge genera to ALC8. Conclusion: In this study, we demonstrated that the structural pattern of the GM differs significantly between MASLD and ALD models. Studies are needed to characterize the microbiota and metabolome in both clinical conditions to find new therapeutic strategies.

RESUMO Contexto: A doença hepática alcoólica (DHA) e a doença hepática esteatótica associada à disfunção metabólica (MASLD) são comuns, e a microbiota intestinal (MI) está envolvida em ambas. Aqui, comparamos a composição da MI em modelos animais de MASLD e DHA para avaliar se existem padrões específicos para cada doença. Métodos: Modelo de MASLD - ratos machos adultos da linhagem Sprague Dawley, randomizados em dois grupos: MASLD-controle (n=10) alimentados com uma dieta padrão; grupo MASLD (n=10) alimentados com uma dieta rica em gordura e deficiente em colina por 16 semanas. Modelo de DHA - ratos machos adultos da linhagem Wistar randomizados: DHA-controle (n=8) alimentados com uma dieta padrão e água+0,05% de sacarina; grupos DHA alimentados com semente de girassol e 10% de etanol+0,05% de sacarina por 4 ou 8 semanas (DHA4, n=8; DHA8, n=8). DHA 4/8 no último dia receberam binge alcoólico (5 g/kg de etanol). Posteriormente, os animais foram sacrificados, e as fezes foram coletadas para análise da MI. Resultados: Ambos os modelos experimentais induziram características histopatológicas típicas das doenças. A diversidade alfa foi menor na MASLD em comparação com a DHA (P<0,001), e o padrão estrutural foi diferente entre elas (P<0,001). Bacteroidetes (55,7%), Firmicutes (40,6%) e Proteobactérias (1,4%) foram os filos mais prevalentes em todas as amostras, embora com abundâncias diferenciadas entre os grupos. DHA8 teve uma maior abundância dos filos Cyanobacteria (5,3%) e Verrucomicrobiota (3,2%) em relação aos outros. A análise de abundância diferencial identificou Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136 e Turicibacter associados ao grupo DHA4, e os gêneros Clostridia_UCG_014_ge e Gastranaerophilales_ge associados ao DHA8. Conclusão: Neste estudo, demonstramos que o padrão estrutural da MI difere significativamente entre os modelos de MASLD e DHA. Estudos são necessários para caracterizar a microbiota e os metabólitos ativos em ambas as condições clínicas, a fim de encontrar novas estratégias terapêuticas.

Quality of life in Brazilian patients with treated or untreated chronic hepatitis C.

INTRODUCTION: Multiple factors negatively affect the quality of life of patients infected with hepatitis C virus. This study aims to evaluate the effect of pharmacological treatment on the quality of life of these individuals. METHODS: This is a cross-sectional study conducted in two Southern Brazilian centers that used two instruments (a generic and a specific one) for measuring the quality of life in patients with chronic hepatitis C: the Short Form-36 (SF-36); and the Chronic Liver Disease Questionnaire (CLDQ) for liver disease. We included patients from two centers without any treatment (control group), or receiving medication (peginterferon + ribavirin ± telaprevir or boceprevir, i.e., respectively, dual, and triple therapies). RESULTS: One hundred and forty-seven patients were included. Patients under treatment (n = 86) had a lower score in 7 of the 8 SF-36 domains, with statistical significance (p<0.05) only for the emotional function domain. Patients who were not treated (n = 58) had higher scores in 4 of the 6 (p<0.05) CLDQ domains. A comparison of patients, receiving dual or triple therapies for both questionnaires, was only significant in the Vitality domain from CLDQ. CONCLUSIONS: Treatment can affect the subjective perception of patients regarding quality of life. Due to the complexity of the disease, each patient must be evaluated in multiple dimensions. Thus, the results may be useful for understanding the patient's perceptions during treatment, and it can also serve as a reference for care instructions.

Circunferência do pescoço como marcador preditivo para síndrome metabólica e risco cardiovascular / Neck circumference as a predictive marker for metabolic syndrome and cardiovascular risk

A circunferência de cintura é há muito tempo o índice padrão para avaliar a gordura abdominal na identificação de pacientes com síndrome metabólica. No entanto, observa-se que uma proporção de doentes com doenças cardiovasculares exibe essa circunferência normal. Assim, o objetivo deste estudo foi avaliar se a circunferência de pescoço pode ser utilizada como marcador preditivo para Síndrome Metabólica e risco cardiovascular. Participaram deste estudo transversal, 42 indivíduos submetidos à avaliação socioeconômica e antropométrica. A circunferência do pescoço correlacionou-se positivamente com a circunferência de cintura, glicemia de jejum, pressão arterial sistólica e diastólica e triglicerídeos. A curva Receiver Operating Characteristic exibiu ponto de corte de 40 cm com alto risco cardiovascular acima deste valor. Os resultados demonstram que a circunferência de pescoço além de rápida e não invasiva pode ser útil na previsão de Síndrome Metabólica e risco cardiovascular. (AU)

Waist circumference has long been the standard index to assess abdominal fat in the identification of patients with Metabolic Syndrome. However, it is observed that a proportion of patients with cardiovascular diseases present abnormal values in this circumference. Thus, the objective of this study was to evaluate whether neck circumference can be used as a predictive marker for Metabolic Syndrome and cardiovascular risk. Forty-two individuals who underwent a socioeconomic and anthropometric evaluation participated in this cross-sectional study. Neck circumference correlated positively with waist circumference, fasting glucose, systolic and diastolic blood pressure, and triglycerides. The ROC curve had a cutoff point of 40 cm, with high cardiovascular risk above this value. The results show that, in addition to being fast and non-invasive, neck circumference can be useful in predicting Metabolic Syndrome and cardiovascular risk. (AU)

Epidemiological and microbiological aspects of residential outbreaks of foodborne illness in the Parana State, Brazil / Aspectos epidemiológicos e microbiológicos dos surtos residenciais de doenças transmitidas por alimentos no Estado do Paraná, Brasil

Foodborne illness results in high costs to public health and the food chain production worldwide. The majority of the population is unaware of food safety requirements and consequently, domestic kitchens are sources of contamination and spread of disease. Eating habits and the profile of food handlers in these sites guide the planning of surveillance and public education. This study describes the epidemiological and microbiological aspects of household outbreaks of foodborne illness in the State of Parana, using the Notifiable Diseases Information System database. There were 357 outbreaks between 2008 and 2012 in the State of Parana, and households were the main place of occurrence (43.70%), followed by restaurants and bakeries (21.00%), and kindergartens and schools (11.20 %). Household outbreak records derived from the municipalities for regional health coverage, based in Curitiba, Cascavel, Pato Branco, Foz do Iguaçu and Londrina. These indicated an increased number of reported cases between 2011 and 2012. The increase in reporting reflects a greater awareness among professionals because of training. The results highlight the consumption of contaminated food (36.15%), by strains of coagulase positive Staphylococcus (36.23%). They also reflect an intensification and wholeness of public policies on the education of the population regarding hygiene principles in the acquisition, handling, preparation, storage, and consumption of food in the household.(AU)

Doenças transmitidas por alimentos representam mundialmente elevados custos à saúde pública e à cadeia produtiva de alimentos. Boa parte da população desconhece os requisitos à segurança dos alimentos tornando as cozinhas domésticas fontes de contaminação e propagação de doenças. Os hábitos alimentares e o perfil dos manipuladores nestes locais norteiam o planejamento da vigilância e educação da população. O presente trabalho descreve os aspectos epidemiológicos e microbiológicos dos surtos residenciais de doenças transmitidas por alimentos no Estado do Paraná, a partir da base de dados do Sistema de Informação de Agravos de Notificação. No período de 2008 a 2012 foram notificados 357 surtos no Estado do Paraná sendo as residências paranaenses o principal local de ocorrência (43,70%), seguidas pelos restaurantes e padarias (21,00%) e pelas creches e escolas (11,20%). Entretanto, os registros de surtos domiciliares mantiveram-se concentrados nos municípios de abrangência das regionais de saúde sediadas em Curitiba, Cascavel, Pato Branco, Foz do Iguaçu e Londrina, com destaque ao aumento de notificação nos anos de 2011 e 2012, que coincide com a sensibilização dos profissionais envolvidos por meio de capacitações. Destacam-se o consumo de alimentos contaminados (36,15%), por cepas de Staphylococcus coagulase positiva (36,23%) e normalmente a base de carnes e seus derivados (59,57%), sugerindo a intensificação e integralidade das políticas públicas na educação da população quanto aos princípios de higiene na aquisição, manipulação, preparação, conservação e consumo dos alimentos nos domicílios.(AU)

Epidemiological and microbiological aspects of residential outbreaks of foodborne illness in the Parana State, Brazil / Aspectos epidemiológicos e microbiológicos dos surtos residenciais de doenças transmitidas por alimentos no Estado do Paraná, Brasil

Foodborne illness results in high costs to public health and the food chain production worldwide. The majority of the population is unaware of food safety requirements and consequently, domestic kitchens are sources of contamination and spread of disease. Eating habits and the profile of food handlers in these sites guide the planning of surveillance and public education. This study describes the epidemiological and microbiological aspects of household outbreaks of foodborne illness in the State of Parana, using the Notifiable Diseases Information System database. There were 357 outbreaks between 2008 and 2012 in the State of Parana, and households were the main place of occurrence (43.70%), followed by restaurants and bakeries (21.00%), and kindergartens and schools (11.20 %). Household outbreak records derived from the municipalities for regional health coverage, based in Curitiba, Cascavel, Pato Branco, Foz do Iguaçu and Londrina. These indicated an increased number of reported cases between 2011 and 2012. The increase in reporting reflects a greater awareness among professionals because of training. The results highlight the consumption of contaminated food (36.15%), by strains of coagulase positive Staphylococcus (36.23%). They also reflect an intensification and wholeness of public policies on the education of the population regarding hygiene principles in the acquisition, handling, preparation, storage, and consumption of food in the household.

Doenças transmitidas por alimentos representam mundialmente elevados custos à saúde pública e à cadeia produtiva de alimentos. Boa parte da população desconhece os requisitos à segurança dos alimentos tornando as cozinhas domésticas fontes de contaminação e propagação de doenças. Os hábitos alimentares e o perfil dos manipuladores nestes locais norteiam o planejamento da vigilância e educação da população. O presente trabalho descreve os aspectos epidemiológicos e microbiológicos dos surtos residenciais de doenças transmitidas por alimentos no Estado do Paraná, a partir da base de dados do Sistema de Informação de Agravos de Notificação. No período de 2008 a 2012 foram notificados 357 surtos no Estado do Paraná sendo as residências paranaenses o principal local de ocorrência (43,70%), seguidas pelos restaurantes e padarias (21,00%) e pelas creches e escolas (11,20%). Entretanto, os registros de surtos domiciliares mantiveram-se concentrados nos municípios de abrangência das regionais de saúde sediadas em Curitiba, Cascavel, Pato Branco, Foz do Iguaçu e Londrina, com destaque ao aumento de notificação nos anos de 2011 e 2012, que coincide com a sensibilização dos profissionais envolvidos por meio de capacitações. Destacam-se o consumo de alimentos contaminados (36,15%), por cepas de Staphylococcus coagulase positiva (36,23%) e normalmente a base de carnes e seus derivados (59,57%), sugerindo a intensificação e integralidade das políticas públicas na educação da população quanto aos princípios de higiene na aquisição, manipulação, preparação, conservação e consumo dos alimentos nos domicílios.