Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver

AIM To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genesin zebrafish.METHODS Zebrafish(n = 104),wild type,adult,male and female,were divided into two groups:Control and ethanol(0.05 v/v).The ethanol was directly added into water;tanks water were changed every two days and the ethanol replaced.The animals were fed twice a day with fish food until satiety.After two and four weeks of trial,livers were dissected,histological analysis(hematoxilineosin and Oil Red staining) and gene expression assessment of adiponectin,adiponectin receptor 2(adipor2),sirtuin-1(sirt-1),tumor necrosis factor-alpha(tnf-a),interleukin-1b(il-1b) and interleukin-10(il-10) were performed.Ultrastructural evaluations were conducted at fourth week.RESULTS Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks,as demonstrated by oil red staining.In ethanol-treated animals,the main ultrastructural changes were related to cytoplasmic lipid particles and droplets,increased number of rough endoplasmic reticulum cisterns and glycogen particles.Between two and four weeks,hepatic mR NA expression of il-1b,sirt-1 and adipor2 were upregulated,indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses.Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol,and il-10 did not show significant difference.CONCLUSION Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis

BACKGROUND Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease,and gut microbiota dysbiosis is associated with both of them.AIM To assess the relationship between gut dysbiosis and cardiovascular risk(CVR)in an experimental model of steatohepatitis.METHODS Adult male Sprague-Dawley rats were randomized to a control group(n=10)fed a standard diet and an intervention group(n=10)fed a high-fat choline-deficient diet for 16 wk.Biochemical,molecular,hepatic,and cardiac histopathology.Gut microbiota variables were evaluated.RESULTS The intervention group had a significantly higher atherogenic coefficient,Castelli’s risk index(CRI)-I and CRI-II,interleukin-1β,tissue inhibitor of metalloproteinase-1(all P<0.001),monocyte chemoattractant protein-1(P=0.005),and plasminogen activator inhibitor-1(P=0.037)than the control group.Gene expression of miR-33a increased(P=0.001)and miR-126(P<0.001)decreased in the intervention group.Steatohepatitis with fibrosis was seen in the intervention group,and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance(P=0.007),reduction in the mean area of cardiomyocytes(P=0.037),and an increase of atrophic cardiomyocytes(P=0.007).There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and CVR.The intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota(both P<0.001)than controls.Nine microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and CVR.CONCLUSION The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.

Cirrhosis in children and adolescents: An overview

Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis,Wilson's disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition.