Aging and Chronic Liver Disease

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.

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

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5719
Author(s):  
Albert Gibert-Ramos ◽  
David Sanfeliu-Redondo ◽  
Peio Aristu-Zabalza ◽  
Ana Martínez-Alcocer ◽  
Jordi Gracia-Sancho ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Current Knowledge ◽  
Cell Types ◽  
Chronic Liver ◽  
Liver Sinusoidal Endothelial Cells ◽  
Chronic Injury ◽  
Unique Type ◽  
Sinusoidal Cells ◽  
Hepatic Sinusoid

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.

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

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 487 ◽  
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.

scholarly journals Imaging Software-Based Sarcopenia Assessment in Gastroenterology: Evolution and Clinical Meaning

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Giovanni Marasco ◽  
Sinan Sadalla ◽  
Giulio Vara ◽  
Rita Golfieri ◽  
Davide Festi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Liver Disease ◽  
Liver Failure ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Cross Sectional ◽  
Cross Sectional Imaging ◽  
Sectional Imaging

Sarcopenia is gaining attention as a negative prognostic factor in different fields of medicine, including chronic liver failure. However, the assessment of sarcopenia in patients with liver diseases is often neglected due to unawareness of reliable tools and methods and thus is limited to research studies. Cross-sectional imaging is a diffuse diagnostic tool and is commonly performed in patients with chronic liver failure. The last advancements in radiology image analysis using dedicated software allow an easy and standardized method to assess skeletal muscle volume. Several measures can be obtained from cross-sectional imaging analysis to evaluate sarcopenia in patients affected by chronic liver disease. We aimed to review the recent advances in imaging-based sarcopenia assessment, in particular in patients with chronic liver diseases. As a result, we found that the skeletal muscle index (SMI) seems to be a reliable method to assess sarcopenia in cirrhotic patients. Even if further studies are needed to validate proper cut-offs for each clinical endpoint, physicians are invited to consider the assessment of sarcopenia in the work-up of patients with chronic liver disease.

scholarly journals Genome-wide transcriptome analysis identifies novel gene signatures implicated in human chronic liver disease

2013 ◽  
Vol 305 (5) ◽  
pp. G364-G374 ◽  
Author(s):  
Rana L. Smalling ◽  
Don A. Delker ◽  
Yuxia Zhang ◽  
Natalia Nieto ◽  
Michael S. Mcguiness ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Liver Function ◽  
Chronic Liver Disease ◽  
Nuclear Receptor ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Rna Seq ◽  
Gene Signatures

The molecular mechanisms behind human liver disease progression to cirrhosis remain elusive. Nuclear receptor small heterodimer partner (SHP/ Nr0b2) is a hepatic tumor suppressor and a critical regulator of liver function. SHP expression is diminished in human cirrhotic livers, suggesting a regulatory role in human liver diseases. The goal of this study was to identify novel SHP-regulated genes that are involved in the development and progression of chronic liver disease. To achieve this, we conducted the first comprehensive RNA sequencing (RNA-seq) analysis of Shp−/− mice, compared the results with human hepatitis C cirrhosis RNA-seq and nonalcoholic steatohepatitis (NASH) microarray datasets, and verified novel results in human liver biospecimens. This approach revealed new gene signatures associated with chronic liver disease and regulated by SHP. Several genes were selected for validation of physiological relevance based on their marked upregulation, novelty with regard to liver function, and involvement in gene pathways related to liver disease. These genes include peptidoglycan recognition protein 2, dual specific phosphatase-4, tetraspanin 4, thrombospondin 1, and SPARC-related modular calcium binding protein-2, which were validated by qPCR analysis of 126 human liver specimens, including steatosis, fibrosis, and NASH, alcohol and hepatitis C cirrhosis, and in mouse models of liver inflammation and injury. This RNA-seq analysis identifies new genes that are regulated by the nuclear receptor SHP and implicated in the molecular pathogenesis of human chronic liver diseases. The results provide valuable transcriptome information for characterizing mechanisms of these diseases.

scholarly journals Expression and Function of Methylthioadenosine Phosphorylase in Chronic Liver Disease

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80703 ◽  
Author(s):  
Barbara Czech ◽  
Katja Dettmer ◽  
Daniela Valletta ◽  
Michael Saugspier ◽  
Andreas Koch ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Methylthioadenosine Phosphorylase ◽  
And Function

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

Biomedicines ◽  
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.

scholarly journals Chapter of Gastroenterologists professional guidance for management of patients with liver disease in Singapore during the COVID-19 pandemic

2020 ◽  
Vol 61 (12) ◽  
pp. 619-623
Author(s):  
PE Chang ◽  
YJ Wong ◽  
WL Yang ◽  
KBL Lim ◽  
PS Tan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
European Association ◽  
American Association ◽  
Chronic Liver ◽  
Published Data ◽  
Professional Guidance

In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.

Gastroenterology

2019 ◽  
Author(s):  
Ricky Sinharay
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Hospital Admissions ◽  
Medical Profession ◽  
Therapeutic Endoscopy ◽  
Chronic Liver ◽  
Molecular Events ◽  
Related Liver Disease ◽  
The Uk ◽  
And Function

Gastroenterology and hepatology encompass a vast array of organs that have diverse structure and function and are affected by a multitude of disease processes. Diseases of the digestive tract are a major cause of morbidity and mortality in the United Kingdom (UK) and worldwide. There have been great advances in our understanding, diagnosis, and management of gastrointestinal (GI) disease, and knowledge continues to develop at a great pace. Understanding the physiology and cellular and molecular events that drive pathological processes, as well as the devel­opment of sophisticated endoscopic and radiological tests, have trans­formed diagnostic capability. Therapeutic endoscopy has progressed to replace surgical management of common GI emergencies such as upper GI tract bleeding and decompressing biliary tract obstruction. However, as ever, there is still much work to be done. For example, the advances in biologic immunotherapy in inflammatory bowel disease has greatly im­proved patients’ quality of life and a reduction in the need for surgery, though the overall impact of these medications on the natural history of the disease is debatable at present. Hepatology is a greatly misunderstood specialty. The physiological changes that occur as cirrhosis and portal hypertension develop are the key to understanding all manifestations of a decompensating liver. Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions have increased. Liver disease is the only major cause of death still increasing year on year, and twice as many people now die from liver disease than in 1991. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol- related liver disease (ARLD) found that less than half the number of patients who died from ARLD received ‘good care’, and avoidable deaths were identified. Allied to this, the enquiry shed light on a cultural pessimism regarding outcomes and prognosis of chronic liver disease and, in particular, ARLD from both the public and the medical profession as a whole. There is now a concerted drive towards improving awareness of chronic liver disease, and initial simple supportive treatments can greatly improve sur­vival, more so than previously thought.

ASSESMENT OF FATIGUE IN PATIENTS WITH CHRONIC LIVER DISEASES

2021 ◽  
pp. 49-53
Author(s):  
М.D. Golubeva ◽  
◽  
К.V. Darafeyeva ◽  
D.E. Danilau ◽  
D.V. Litvinchuk ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
Short Form ◽  
Chronic Liver ◽  
Assessment Scale ◽  
Chronic Liver Diseases ◽  
Fatigue Assessment ◽  
Chronic Liver Disease Questionnaire ◽  
Disease Questionnaire

To determine the most sensitive questionnaire for the detection of fatigue in patients with chronic liver diseases, 61 patients with chronic liver diseases were inpatient treatment at the City Infectious Diseases Clinical were interviewed. And 72 relatively healthy responses were interviewed using Chronic Liver Disease Questionnaire, the Short Form-36, the Fatigue Assessment Scale. The study was conducted between November 2019 and March 2020. The severity of fatigue and declining quality of life was correlated with the presence of chronic liver diseases, excess body weight, and female sex. The Short Form-36 questionnaire showed greater sensitivity for assessing fatigue in people with chronic liver diseases compared to the Chronic Liver Disease Questionnaire. The Fatigue Assessment Scale didn't reveal reliable differences between the groups being compared.

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