RESUMO
Liver diseases have a global prevalence of 25%, accounting for 4% of all deaths worldwide, and are associated with a 36% increased risk of fatal and nonfatal cardiovascular events. Metabolic dysfunction-associated steatotic liver disease constitutes the liver expression of metabolic syndrome and represents the primary type of liver disease. Microscopical analysis of biopsies, which allows the evaluation of a small portion of tissue with inferences made to the entire organ, is considered the gold standard for determining the presence of liver diseases. However, potential sampling errors in liver biopsies are conceivable because the obtained tissue represents only a tiny fraction of the entire liver mass and may not accurately reflect the true pathological state. Studies have demonstrated the existence of sampling errors in liver biopsies, particularly concerning the severity of inflammation, degree of fibrosis, and the presence of cirrhosis. Also, clinical studies have shown that histopathological abnormalities are better detected in humans when liver samples are collected from both the right and the left lobes. However, a gap exists in clinical investigation to clarify the role of differences between these lobes in improving the diagnostic and prognostic for liver diseases. Building upon the heterogeneous nature of pathological alterations observed in liver lobes, this perspective review provided recommendations to enhance the precision of diagnosis and prognostic accuracy of liver diseases.
Assuntos
Hepatopatias , Fígado , Humanos , Fígado/patologia , Hepatopatias/patologia , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Biópsia , Prognóstico , Síndrome Metabólica/patologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/diagnóstico , Cirrose Hepática/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , AnimaisRESUMO
INTRODUCTION AND OBJECTIVES: Assessment of liver inflammation plays a vital role in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate a nomogram to predict severe liver inflammation in AIH patients. PATIENTS AND METHODS: AIH patients who underwent liver biopsy were included and randomly divided into a training set and a validation set. Independent predictors of severe liver inflammation were selected by the least absolute shrinkage and selection operator regression from the training set and used to conduct a nomogram. Receiver characteristic curves (ROC), calibration curves, and decision curve analysis (DCA) were adopted to evaluate the performance of nomogram. RESULTS: Of the 213 patients, female patients accounted for 83.1% and the median age was 53.0 years. The albumin, gamma-glutamyl transpeptidase, total bilirubin, red cell distribution width, prothrombin time, and platelets were independent predictors of severe inflammation. An online AIHI-nomogram was established and was available at https://ndth-zzy.shinyapps.io/AIHI-nomogram/. The calibration curve revealed that the AIHI-nomogram had a good agreement with actual observation in the training and validation sets. The area under the ROCs of AIHI-nomogram were 0.795 in the training set and 0.759 in the validation set, showing significantly better performance than alanine aminotransferase and immunoglobulin G in the training and validation sets, as well in AIH patients with normal ALT in the training set. DCA indicated that the AIHI-nomogram was clinically useful. CONCLUSIONS: This novel AIHI-nomogram provided an excellent prediction of severe liver inflammation in AIH patients and could be used for the better management of AIH.
RESUMO
It is well established that diets containing an increased omega-6 polyunsaturated fatty acid (n-6 PUFA) to omega-3 polyunsaturated fatty acid (n-3 PUFA) ratios are linked to inflammation and chronic diseases such as nonalcoholic fatty liver disease (NAFLD). However, the influence of an elevated n-6 PUFA:n-3 PUFA ratio in the tissues requires clarification. Herein, we identified primary experimental and clinical studies where it is possible to compare the performance of the myristic acid (Myr):docosahexaenoic acid (DHA) and n-6 PUFA:n-3 PUFA ratios in the liver and/or serum as potential NAFLD biomarkers. Articles were included if quantitative values of n-6 PUFA, n-3 PUFA, Myr, DHA, and information about liver inflammation or liver disease progression parameters were provided. Overall, most experimental (91.6%) and clinical studies (87.5%) reported higher Myr:DHA ratios associated with inflammation and/or NAFLD progression than the n-6 PUFA:n-3 PUFA ratio. We conclude that the Myr:DHA ratio represents a better biomarker of NAFLD than the n-6 PUFA:n-3 PUFA ratio. Future studies are necessary for verifying this observation.
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Ácidos Graxos Ômega-3 , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-6 , Humanos , Inflamação , Ácido Mirístico , Hepatopatia Gordurosa não Alcoólica/diagnósticoRESUMO
Citrate is widely used as a food additive being part of virtually all processed foods. Although considered inert by most of the regulatory agencies in the world, plasma citrate has been proposed to play immunometabolic functions in multiple tissues through altering a plethora of cellular pathways. Here, we used a short-term alimentary intervention (24 hours) with standard chow supplemented with citrate in amount corresponding to that found in processed foods to evaluate its effects on glucose homeostasis and liver physiology in C57BL/6J mice. Animals supplemented with dietary citrate showed glucose intolerance and insulin resistance as revealed by glucose and insulin tolerance tests. Moreover, animals supplemented with citrate in their food displayed fed and fasted hyperinsulinemia and enhanced insulin secretion during an oral glucose tolerance test. Citrate treatment also amplified glucose-induced insulin secretion in vitro in INS1-E cells. Citrate supplemented animals had increased liver PKCα activity and altered phosphorylation at serine or threonine residues of components of insulin signaling including IRS-1, Akt, GSK-3 and FoxO1. Furthermore, citrate supplementation enhanced the hepatic expression of lipogenic genes suggesting increased de novo lipogenesis, a finding that was reproduced after citrate treatment of hepatic FAO cells. Finally, liver inflammation markers were higher in citrate supplemented animals. Overall, the results demonstrate that dietary citrate supplementation in mice causes hyperinsulinemia and insulin resistance both in vivo and in vitro, and therefore call for a note of caution on the use of citrate as a food additive given its potential role in metabolic dysregulation.
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Ácido Cítrico/farmacologia , Inflamação/metabolismo , Resistência à Insulina , Fígado/metabolismo , Animais , Ácido Cítrico/efeitos adversos , Dieta , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Quinase 3 da Glicogênio Sintase/metabolismo , Hepatócitos/metabolismo , Homeostase , Hiperinsulinismo/etiologia , Insulina/metabolismo , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologiaRESUMO
BACKGROUND: Malnutrition and accessible high-quality protein food sources are two of the world's alimentary challenges. Edible insects are nowadays recognized as a possible functional food solution with lower environmental impacts and beneficial health effects. OBJECTIVE: In this context, the aim of the present study is to evaluate Madagascar cockroach (Gromphadorhina portentosa) flour supplementation effects on a malnourished mice model, considering its effects on metabolism, adiposity, and inflammatory liver profiles. METHOD: Male Swiss mice are divided into five groups and fed with experimental diets for eight weeks, including a standard diet (ST) ad libitum, AIN93 ad libitum (AIN), insect flour-enriched AIN93 (AIN+IM), AIN-40% feed restriction (AIN-FR), and insect flour-enriched AIN-40% of feed restriction (AIN-FR+IM). The metabolic profiles, adipose tissue, biochemical parameters, and liver IL-6 and IL-10 expression are evaluated. RESULTS: The main findings show a body weight and metabolism improvement followed by an increased recovery of the adipocyte area in the AIN-FR+IM group when compared to the AIN-FR malnourished group. Reduced hepatic IL-6 and increased IL-10 expression are also detected in the AIN-FR+IM group. CONCLUSION: The results show that insect flour supplementation enhances both body weight and adiposity gain/recovery. The results also show hepatic improvement of inflammatory markers.
Assuntos
Baratas , Desnutrição , Animais , Dieta , Suplementos Nutricionais , Farinha , Fígado , Madagáscar , Masculino , Camundongos , Patentes como AssuntoRESUMO
INTRODUCTION AND AIM: Natural Killer (NK) cells play an important role in innate immune response to viral infections and their high proportion is situated in the liver. The aim of this study was to analyze possible relation between the expression of NK cell receptors and varied intensity of liver lesions in chronic hepatitis C (CHC) in children. MATERIAL AND METHODS: Study included 105 children with CHC - 54 boys and 51 girls, age 13.62 ± 3.48 years. Blood specimens were taken at the day of the liver biopsy. Histological evaluation was performed according to METAVIR scoring system. Circulating NK cells were evaluated by flow cytometry. The results were shown as a proportion of cells expressing evaluated receptor and its' mean fluorescent intensity (MFI). RESULTS: In 58 children with CHC (55.2%) significant liver fibrosis was observed ( ≥F2). Higher proportion of cells expressing CD158e inhibitory receptors was observed in the group of children with ALT > 2UNL (21.11 ± 14.60 vs. 12.22 ± 8.99%; p = 0.037). While higher proportion of cells expressing inhibitory CD158b receptor was observed in children with significant fibrosis (F ≥ 2) compared to minimal fibrosis (F < 2) - (34.14 ± 12.44 vs. 27.48 ± 8.71%; p = 0.049). Children with advanced fibrosis (F ≥ 3) had higher MFI of NK cell CD 158b receptor than children with fibrosis scored F < 3 - (5344.20 ± 3407.49 vs. 2979.67 ± 1190.64; p = 0.049). Proportion of NK cells expressing CD158b was found a predictor of significant fibrosis in univariate analysis - [OR 1.065; 95%CI (1.07-1.15); p = 0.046]. CONCLUSIONS: Higher proportion of NK cells expressing inhibitory CD158b and CD158e receptors is associated with significant liver injury.
Assuntos
Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Fígado/patologia , Células T Matadoras Naturais/imunologia , Receptores KIR2DL3/sangue , Receptores KIR3DL1/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Biópsia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Hepacivirus/patogenicidade , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Interações Hospedeiro-Patógeno , Humanos , Fígado/virologia , Cirrose Hepática/sangue , Cirrose Hepática/virologia , Masculino , Análise Multivariada , Células T Matadoras Naturais/virologia , Razão de Chances , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 µL, CTRL) or different doses of MCLR (5 µg/kg, TOX5), 10 µg/kg (TOX10), 15 µg/kg (TOX15) and 20 µg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group.