The Hepatic Sinusoid in Chronic Liver Disease: The Optimal Milieu for Cancer

The liver sinusoids are a unique type of microvascular beds. The specialized phenotype of sinusoidal cells is essential for their communication, and for the function of all hepatic cell types, including hepatocytes. Liver sinusoidal endothelial cells (LSECs) conform the inner layer of the sinusoids, which is permeable due to the fenestrae across the cytoplasm; hepatic stellate cells (HSCs) surround LSECs, regulate the vascular tone, and synthetize the extracellular matrix, and Kupffer cells (KCs) are the liver-resident macrophages. Upon injury, the harmonic equilibrium in sinusoidal communication is disrupted, leading to phenotypic alterations that may affect the function of the whole liver if the damage persists. Understanding how the specialized sinusoidal cells work in coordination with each other in healthy livers and chronic liver disease is of the utmost importance for the discovery of new therapeutic targets and the design of novel pharmacological strategies. In this manuscript, we summarize the current knowledge on the role of sinusoidal cells and their communication both in health and chronic liver diseases, and their potential pharmacologic modulation. Finally, we discuss how alterations occurring during chronic injury may contribute to the development of hepatocellular carcinoma, which is usually developed in the background of chronic liver disease.

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The Influence of Chronic Liver Diseases on Hepatic Vasculature: A Liver-on-a-chip Review

Micromachines ◽

10.3390/mi11050487 ◽

2020 ◽

Vol 11 (5) ◽

pp. 487 ◽

Cited By ~ 1

Author(s):

Alican Özkan ◽

Danielle Stolley ◽

Erik N. K. Cressman ◽

Matthew McMillin ◽

Sharon DeMorrow ◽

...

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Liver Diseases ◽

Recent Literature ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Liver Sinusoidal Endothelial Cells ◽

Chronic Injury ◽

Hepatic Vasculature

In chronic liver diseases and hepatocellular carcinoma, the cells and extracellular matrix of the liver undergo significant alteration in response to chronic injury. Recent literature has highlighted the critical, but less studied, role of the liver vasculature in the progression of chronic liver diseases. Recent advancements in liver-on-a-chip systems has allowed in depth investigation of the role that the hepatic vasculature plays both in response to, and progression of, chronic liver disease. In this review, we first introduce the structure, gradients, mechanical properties, and cellular composition of the liver and describe how these factors influence the vasculature. We summarize state-of-the-art vascularized liver-on-a-chip platforms for investigating biological models of chronic liver disease and their influence on the liver sinusoidal endothelial cells of the hepatic vasculature. We conclude with a discussion of how future developments in the field may affect the study of chronic liver diseases, and drug development and testing.

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Aging and Chronic Liver Disease

Seminars in Liver Disease ◽

10.1055/s-0040-1715446 ◽

2020 ◽

Vol 40 (04) ◽

pp. 373-384

Author(s):

Raquel Maeso-Díaz ◽

Jordi Gracia-Sancho

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Liver Diseases ◽

Experimental Models ◽

Chronic Liver ◽

Liver Sinusoidal Endothelial Cells ◽

Hepatic Sinusoid ◽

Age Related ◽

Effects Of Aging ◽

And Function

AbstractAging increases the incidence of chronic liver disease (CLD), worsens its prognosis, and represents the predominant risk factor for its development at all different stages. The hepatic sinusoid, which is fundamental for maintaining liver homeostasis, is composed by hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic macrophages. During CLD progression, hepatic cells suffer deregulations in their phenotype, which ultimately lead to disease development. The effects of aging on the hepatic sinusoid phenotype and function are not well understood, nevertheless, studies performed in experimental models of liver diseases and aging demonstrate alterations in all hepatic sinusoidal cells. This review provides an updated description of age-related changes in the hepatic sinusoid and discusses the implications for CLD development and treatment. Lastly, we propose aging as a novel therapeutic target to treat liver diseases and summarize the most promising therapies to prevent or improve CLD and extend healthspan.

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Metabolic Fatty Liver Disease in Children: A Growing Public Health Problem

Biomedicines ◽

10.3390/biomedicines9121915 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1915

Author(s):

Sébastien Le Garf ◽

Véronique Nègre ◽

Rodolphe Anty ◽

Philippe Gual

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Chronic Liver Disease ◽

Fatty Liver Disease ◽

Liver Diseases ◽

Current Knowledge ◽

Public Health Problem ◽

Overweight And Obesity ◽

Chronic Liver ◽

Nonalcoholic Fatty Liver

Metabolic-associated fatty liver disease (MAFLD), previously called nonalcoholic fatty liver diseases (NAFLD), is one of the most important causes of chronic liver disease worldwide and will likely become the leading cause of end-stage liver disease in the decades ahead. MAFLD covers a continuum of liver diseases from fatty liver to nonalcoholic steatohepatitis (NASH), liver fibrosis/cirrhosis and hepatocellular cancer. Importantly, the growing incidence of overweight and obesity in childhood, 4% in 1975 to 18% in 2016, with persisting obesity complications into adulthood, is likely to be harmful by increasing the incidence of severe MAFLD at an earlier age. Currently, MAFLD is the leading form of chronic liver disease in children and adolescents, with a global prevalence of 3 to 10%, pointing out that early diagnosis is therefore crucial. In this review, we highlight the current knowledge concerning the epidemiology, risk factors and potential pathogenic mechanisms, as well as diagnostic and therapeutic approaches, of pediatric MAFLD.

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Oxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical

Nutrients ◽

10.3390/nu12092627 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2627 ◽

Cited By ~ 1

Author(s):

Zoe Boyer-Diaz ◽

Paloma Morata ◽

Peio Aristu-Zabalza ◽

Albert Gibert-Ramos ◽

Jaime Bosch ◽

...

Keyword(s):

Public Health ◽

Oxidative Stress ◽

Portal Hypertension ◽

Liver Disease ◽

Docosahexaenoic Acid ◽

Chronic Liver Disease ◽

Current Knowledge ◽

Chronic Liver ◽

Public Health Issue ◽

Clinical Scenarios

Chronic liver disease constitutes a growing public health issue worldwide, with no safe and effective enough treatment clinical scenarios. The present review provides an overview of the current knowledge regarding advanced chronic liver disease (ACLD), focusing on the major contributors of its pathophysiology: inflammation, oxidative stress, fibrosis and portal hypertension. We present the benefits of supplementation with docosahexaenoic acid triglycerides (TG-DHA) in other health areas as demonstrated experimentally, and explore its potential as a novel nutraceutical approach for the treatment of ACLD and portal hypertension based on published pre-clinical data.

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Human Amnion Epithelial Cell Therapy for Chronic Liver Disease

Stem Cells International ◽

10.1155/2019/8106482 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Neil Andrewartha ◽

George Yeoh

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Epithelial Cells ◽

Chronic Liver Disease ◽

Cell Types ◽

Chronic Liver ◽

Human Amnion ◽

Curative Therapy ◽

Cell Based Therapy ◽

Amnion Epithelial Cells

Liver fibrosis is a common consequence of chronic liver disease. Over time, liver fibrosis can develop into liver cirrhosis. Current therapies for liver fibrosis are limited, and liver transplant is the only curative therapy for patients who progress to end-stage disease. A potential approach to treat chronic liver disease with increasing interest is cell-based therapy. Among the multiple cell types which have been proposed for therapeutic uses, human amnion epithelial cells and amniotic fluid-derived mesenchymal cells are promising. These cells are highly abundant, and their use poses no ethical concern. Furthermore, they exert potent anti-inflammatory and antifibrotic effects in animal models of liver injury. This review highlights the therapeutic characteristics and discusses how human amnion epithelial cells can be utilised as a therapeutic tool for chronic liver disease.

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Animal and Organoid Models of Liver Fibrosis

Frontiers in Physiology ◽

10.3389/fphys.2021.666138 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu-long Bao ◽

Li Wang ◽

Hai-ting Pan ◽

Tai-ran Zhang ◽

Ya-hong Chen ◽

...

Keyword(s):

Animal Model ◽

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Hepatic Fibrosis ◽

Physiological State ◽

Chronic Liver ◽

Chronic Injury ◽

Suitable Animal Model ◽

Depth Study

Liver fibrosis refers to the process underlying the development of chronic liver diseases, wherein liver cells are repeatedly destroyed and regenerated, which leads to an excessive deposition and abnormal distribution of the extracellular matrix such as collagen, glycoprotein and proteoglycan in the liver. Liver fibrosis thus constitutes the pathological repair response of the liver to chronic injury. Hepatic fibrosis is a key step in the progression of chronic liver disease to cirrhosis and an important factor affecting the prognosis of chronic liver disease. Further development of liver fibrosis may lead to structural disorders of the liver, nodular regeneration of hepatocytes and the formation of cirrhosis. Hepatic fibrosis is histologically reversible if treated aggressively during this period, but when fibrosis progresses to the stage of cirrhosis, reversal is very difficult, resulting in a poor prognosis. There are many causes of liver fibrosis, including liver injury caused by drugs, viral hepatitis, alcoholic liver, fatty liver and autoimmune disease. The mechanism underlying hepatic fibrosis differs among etiologies. The establishment of an appropriate animal model of liver fibrosis is not only an important basis for the in-depth study of the pathogenesis of liver fibrosis but also an important means for clinical experts to select drugs for the prevention and treatment of liver fibrosis. The present study focused on the modeling methods and fibrosis characteristics of different animal models of liver fibrosis, such as a chemical-induced liver fibrosis model, autoimmune liver fibrosis model, cholestatic liver fibrosis model, alcoholic liver fibrosis model and non-alcoholic liver fibrosis model. In addition, we also summarize the research and application prospects concerning new organoids in liver fibrosis models proposed in recent years. A suitable animal model of liver fibrosis and organoid fibrosis model that closely resemble the physiological state of the human body will provide bases for the in-depth study of the pathogenesis of liver fibrosis and the development of therapeutic drugs.

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Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis

Mediators of Inflammation ◽

10.1155/2015/872152 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 43

Author(s):

Hiroki Nishikawa ◽

Yukio Osaki

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Nutritional Status ◽

Chronic Liver Disease ◽

Current Knowledge ◽

Protein Energy Malnutrition ◽

Chronic Liver ◽

Noninvasive Methods ◽

Protein Energy ◽

Single Disease Entity

The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes.

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