scholarly journals Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Nancy Magee ◽  
An Zou ◽  
Yuxia Zhang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Immune Cell ◽  
Health Concern ◽  
Nonalcoholic Fatty Liver ◽  
Liver Parenchymal ◽  
Nonparenchymal Cells ◽  
The Metabolic Syndrome

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning), inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER) stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.

scholarly journals Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals

2019 ◽  
Vol 316 (4) ◽  
pp. G462-G472 ◽  
Author(s):  
Malte P. Suppli ◽  
Kristoffer T. G. Rigbolt ◽  
Sanne S. Veidal ◽  
Sara Heebøll ◽  
Peter Lykke Eriksen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Normal Weight ◽  
Histological Techniques ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Hepatic Transcriptome

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis were performed on liver biopsies obtained from healthy normal-weight ( n = 14) and obese ( n = 12) individuals, NAFL ( n = 15) and NASH ( n = 16) patients. Normal-weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling, and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared with NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD. NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcoholic steatohepatitis (NASH), and ultimately lead to irreversible liver damage. Using gold standard molecular and histological techniques, this study demonstrates that the currently used diagnostic tools are problematic for differentiating mild NAFLD from NASH and emphasizes the marked need for developing improved histological markers of NAFLD progression.

scholarly journals The Role of Innate Immune Cells in Nonalcoholic Fatty Liver Disease

2021 ◽  
pp. 1-11
Author(s):  
Marina Nati ◽  
Kyoung-Jin Chung ◽  
Triantafyllos Chavakis
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Immune Cell ◽  
Innate Immune ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Recent Developments ◽  
Macrophage Populations

Nonalcoholic fatty liver disease (NAFLD) is a very common hepatic pathology featuring steatosis and is linked to obesity and related conditions, such as the metabolic syndrome. When hepatic steatosis is accompanied by inflammation, the disorder is defined as nonalcoholic steatohepatitis (NASH), which in turn can progress toward fibrosis development that can ultimately result in cirrhosis. Cells of innate immunity, such as neutrophils or macrophages, are central regulators of NASH-related inflammation. Recent studies utilizing new experimental technologies, such as single-cell RNA sequencing, have revealed substantial heterogeneity within the macrophage populations of the liver, suggesting distinct functions of liver-resident Kupffer cells and recruited monocyte-derived macrophages with regards to regulation of liver inflammation and progression of NASH pathogenesis. Herein, we discuss recent developments concerning the function of innate immune cell subsets in NAFLD and NASH.

scholarly journals NASH and Systemic Complications: From Basic to Clinical Research

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1913
Author(s):  
Sabine Baumgartner ◽  
Ronit Shiri-Sverdlov
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Clinical Research ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Systemic Complications ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome

Nonalcoholic fatty liver disease (NAFLD) is known as the hepatic manifestation of the metabolic syndrome, and while most patients develop simple steatosis, up to one-third can develop nonalcoholic steatohepatitis (NASH). [...]

Cardiovascular Risk in Children with Nonalcoholic Fatty Liver Disease (NAFLD)

2020 ◽  
Vol 16 ◽  
Author(s):  
Anna Bobrus- Chociej ◽  
Natalia Wasilewska ◽  
Marta Flisiak- Jackiewicz ◽  
Dariusz Lebensztejn
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Scientific Evidence ◽  
Multisystem Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Obesity Epidemic ◽  
The Metabolic Syndrome

: Nonalcoholic fatty liver disease (NAFLD) is a main cause of chronic liver disease in children. With the global obesity epidemic, the prevalence of NAFLD is increasing both in industrialized and developing countries. NAFLD is a multisystem disorder and a hepatic manifestation of the metabolic syndrome. Growing scientific evidence suggests that NAFLD is an independent risk factor for cardiovascular disease. This paper briefly describes the current knowledge concerning the association between NAFLD and cardiac dysfunction in children.

Pathological findings of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease

2016 ◽  
Vol 67 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Michiie Sakamoto ◽  
Hanako Tsujikawa ◽  
Kathryn Effendi ◽  
Hidenori Ojima ◽  
Kenichi Harada ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Pathological Findings ◽  
Nonalcoholic Fatty Liver

scholarly journals Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Response To Treatment ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Overlapping Mechanisms

2021 ◽  
Author(s):  
Søren Møller ◽  
Nina Kimer ◽  
Thit Kronborg ◽  
Josephine Grandt ◽  
Jens Dahlgaard Hove ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Severe Form ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Near Future

AbstractNonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.

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