scholarly journals The fat droplet in hepatocellular ballooning and implications for scoring nonalcoholic steatohepatitis therapeutic response

Hepatology ◽  
2015 ◽  
Vol 63 (3) ◽  
pp. 1056-1057 ◽  
Author(s):  
Curtis K. Argo ◽  
Yoshihiro Ikura ◽  
Carolin Lackner ◽  
Stephen H. Caldwell
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Therapeutic Response ◽  
Hepatocellular Ballooning

Association between dietary total antioxidant capacity and hepatocellular ballooning in nonalcoholic steatohepatitis: a cross-sectional study

2018 ◽  
Vol 58 (6) ◽  
pp. 2263-2270 ◽  
Author(s):  
Daiane Gonçalves de Oliveira ◽  
Fabiana de Faria Ghetti ◽  
Ana Paula Boroni Moreira ◽  
Helen Hermana Miranda Hermsdorff ◽  
Juliano Machado de Oliveira ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Nonalcoholic Steatohepatitis ◽  
Total Antioxidant Capacity ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Total Antioxidant ◽  
Hepatocellular Ballooning ◽  
Dietary Total Antioxidant Capacity

scholarly journals Circulating Neutrophils of Nonalcoholic Steatohepatitis Patients Show an Activated Phenotype and Suppress T Lymphocytes Activity

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Laura Antonucci ◽  
Cristiana Porcu ◽  
Eleonora Timperi ◽  
Silvano Junior Santini ◽  
Gino Iannucci ◽  
...  
Keyword(s):  
T Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Liver Tissue ◽  
Ex Vivo ◽  
Polymorphonuclear Neutrophils ◽  
Resting Cells ◽  
Strongly Correlated ◽  
Effector Cells ◽  
Effector Functions ◽  
Hepatocellular Ballooning

Neutrophils or PolyMorphonuclear Neutrophils (PMNs) are key effector cells of the innate immune system and thanks to their remarkable plasticity, establish a cross talk with T cells modulating their survival and effector functions. During Nonalcoholic Steatohepatitis (NASH), the advanced form of hepatic steatosis or NAFL, PMNs infiltrate liver tissue, becoming a histological feature of NASH. Our aim was to evaluate the frequency of PMNs in NAFL and NASH patients in order to understand how they modulate the activity of circulating CD4+ and CD8+ T cells. In our cohort of patients, NASH patients displayed a higher frequency of circulating PMNs that was strongly correlated to liver enzymes, grade of steatosis, inflammation and fibrosis, the hepatocellular ballooning, and NAFLD Activity Score (NAS). Furthermore, even if ex vivo, in both groups of patients, PMNs shared the same phenotype of resting cells, after 24 hours of coculture with autologous CD4+ and CD8+ T cells, PMNs of NASH patients acquired a more active phenotype, becoming able to strongly inhibit proliferation and activation of CD4+ and CD8+ T cells. The higher ability of PMNs of NASH patients in suppressing CD4+ and CD8+ T cells, over time, might contribute in reducing the immunological defense of liver tissue against damages thus taking part in the progression of the NAFL disease toward NASH.

Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice

2016 ◽  
Vol 310 (2) ◽  
pp. G117-G127 ◽  
Author(s):  
Priya Handa ◽  
Vicki Morgan-Stevenson ◽  
Bryan D. Maliken ◽  
James E. Nelson ◽  
Shenna Washington ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Nonalcoholic Steatohepatitis ◽  
Immune Cell ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Dietary Iron ◽  
Antioxidant Genes ◽  
Hepatic Oxidative Stress ◽  
Hepatocellular Ballooning

The aim of this study was to determine the effect of iron overload in the development of nonalcoholic steatohepatitis (NASH) in a genetically obese mouse model (Lepr db/db). Leptin receptor-deficient mice were fed a normal or an iron-supplemented chow for 8 wk and switched to normal chow for 8 wk. All dietary iron (DI)-fed mice developed hepatic iron overload predominantly in the reticuloendothelial system. Hepatocellular ballooning injury was observed in the livers of 85% of DI mice, relative to 20% of chow-fed Lepr db/db. Hepatic malonyldialdehyde levels and mRNA levels of antioxidant genes ( Nrf2, Gpx1, and Hmox1) were significantly increased in the DI mice. Hepatic mRNA levels of mitochondrial biogenesis regulators Pgc1α, Tfam, Cox4, and Nrf1 were diminished in the DI mice. In addition, gene expression levels of cytokines ( Il6, Tnfα) and several innate and adaptive immune cell markers such as Tlr4, Inos, CD11c, CD4, CD8, and Ifnγ were significantly increased in livers of the DI group. Strikingly, Nlrp3, a component of the inflammasome and Il18, a cytokine elicited by inflammasome activation, were significantly upregulated in the livers of DI mice. In addition, RAW 264.7 macrophages loaded with exogenous iron showed significantly higher levels of inflammatory markers ( Inos, Tnfα, Mcp1, Tlr4). Thus dietary iron excess leads to hepatic oxidative stress, inflammasome activation, induction of inflammatory and immune mediators, hepatocellular ballooning injury, and therefore NASH in this model. Taken together, these studies indicate a multifactorial role for iron overload in the pathogenesis of NASH in the setting of obesity and metabolic syndrome.

scholarly journals Potential benefits of antihypertensive therapy in NAFLD: results from an experimental model

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.C Soares Sturzeneker ◽  
D.B Precoma ◽  
L Noronha ◽  
M Olandoski ◽  
G.A Broday ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Nonalcoholic Steatohepatitis ◽  
Renin Angiotensin System ◽  
Activity Score ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Hypercholesterolemic Diet ◽  
Hepatocellular Ballooning ◽  
Nafld Activity Score ◽  
Lobular Inflammation

Abstract Background and introduction Non-alcoholic fatty liver disease (NAFLD) is considered as the most frequent cause of chronic hepatic disease in adults. It is strictly correlated with insulin resistance. The renin-angiotensin system (RAS) has been correlated to the whole basic physiopathogenic mechanism of NAFLD in experimental models. Systemic arterial hypertension has been suggested to be associated with NAFLD in approximately 40% of the cases, and NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies. Therefore, we can infer that treating arterial hypertension in NAFLD carriers will often be necessary and that the potential beneficial effects of the antihypertensive might, in this context, influence the choice of the respective drug. Purpose We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, both used preventively, in NAFLD induced in rabbits fed a hypercholesterolemic diet and compared the results between the groups. Methods Forty-one rabbits were divided into four groups (normal, control, olmesartan and ramipril). The control, olmesartan and ramipril group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day and animals from ramipril group with ramipril 0.35 mg/kg/day. At the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD. Results The comparison between two groups (olmesartan with placebo and ramipril with placebo) showed that olmesartan and ramipril significantly diminished the development of steatosis (p=0.015, p=0.032), lobular inflammation (p<0.001, p=0.006), hepatocellular ballooning (p<0.001, p=0.023) and fibrosis (p=0.001, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p<0.001, p=0.003). The comparison between olmesartan and ramipril showed that results were similar in all histological parameters evaluated (p=1, p=0.454, p=0.454, p=0.195, p=0.078). Conclusion(s) The preventive use of olmesartan and ramipril attenuates similarly, the development of hepatic steatosis, lobular inflammation, hepatocellular ballooning and fibrosis in hypercholesterolemic rabbits and based on NAFLD activity score both significantly reduced the development of nonalcoholic steatohepatitis. Funding Acknowledgement Type of funding source: None

Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis

2018 ◽  
Vol 88 (5-6) ◽  
pp. 263-269
Author(s):  
Seong-Hoon Park ◽  
A Lum Han ◽  
Na-Hyung Kim ◽  
Sae-Ron Shin
Keyword(s):  
Liver Biopsy ◽  
Vitamin C ◽  
Nonalcoholic Steatohepatitis ◽  
Guinea Pigs ◽  
Normal Diet ◽  
High Dose ◽  
Biochemical Tests ◽  
Deficient Diet ◽  
Histological Improvement ◽  
Vit C

Abstract. Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

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