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

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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The Role of the Gut Microbiome in Liver Cirrhosis Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22010199 ◽

2020 ◽

Vol 22 (1) ◽

pp. 199

Author(s):

Na Young Lee ◽

Ki Tae Suk

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Liver Fibrosis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Liver Diseases ◽

Sclerosing Cholangitis ◽

Chronic Liver ◽

Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

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Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis

International Journal of Hepatology ◽

10.1155/2012/648915 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 56

Author(s):

Jayashree Bagchi Chakraborty ◽

Fiona Oakley ◽

Meagan J. Walsh

Keyword(s):

Liver Disease ◽

Liver Diseases ◽

Recent Literature ◽

Primary Source ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Viral Hepatitis B ◽

Fibrotic Scar ◽

Fibrosis Regression ◽

Nonalcoholic Liver Disease

Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD) nonalcoholic liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) viral hepatitis B and C (HBV, HCV). The critical step in the development of scar is activation of hepatic stellate cells (HSCs), which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression.

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

Cancers ◽

10.3390/cancers13225719 ◽

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.

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ASSESMENT OF FATIGUE IN PATIENTS WITH CHRONIC LIVER DISEASES

Medical Journal ◽

10.51922/1818-426x.2021.3.49 ◽

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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LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms21082883 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2883

Author(s):

Young-Ah Kim ◽

Kwan-Kyu Park ◽

Sun-Jae Lee

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Chronic Liver Disease ◽

Hepatic Fibrosis ◽

Liver Diseases ◽

Molecular Mechanisms ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Nonalcoholic Fatty Liver ◽

Underlying Mechanisms

Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

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POS1385 AUTOIMMUNE DISEASES ASSOCIATED WITH CHRONIC LIVER DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4288 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 975.2-975

Author(s):

N. Trad ◽

G. Mohamed ◽

B. Ben Slimen ◽

K. Boughoula ◽

S. Bizid ◽

...

Keyword(s):

Liver Disease ◽

Autoimmune Diseases ◽

Viral Infection ◽

Chronic Liver Disease ◽

Liver Diseases ◽

Female Gender ◽

Chronic Liver ◽

Primary Biliary Cholangitis ◽

Chronic Liver Diseases ◽

Systematic Screening

Background:Chronic liver diseases whatever their etiologies could be associated with immunological disturbances.Objectives:Our aim was to evaluate the prevalence and the characteristics of autoimmune diseases associated with chronic liver diseases.Methods:We performed a retrospective analysis of data from consecutive patients followed in our department for chronic liver diseases recruited from January 2010 to December 2019. Demographic, clinical, and paraclinical data were collected.Results:A total of 224 patients were included. The mean age was 61.02 ±13.2 years and the sex-ratio was 1.6. The main etiology of chronic liver diseases was viral infection C (32.1%) followed by viral infection B (22.8%) and non-alcoholic steatohepatitis (21.4%). The prevalence of autoimmune chronic liver diseases was 7.58%: autoimmune hepatitis (AIH) in four cases, primary biliary cholangitis (PBC) in huit cases, primary sclerosing cholangitis (PSC) in three cases and overlap syndrome (AIH-PBC) in two cases. Autoimmune diseases were noted in 31 cases (13.9%): autoimmune hemolytic anemia in 15 cases, autoimmune thyroiditis in 12 cases, one case of psoriasis, one case of CREST syndrome, one case of Sjögren’s syndrome and one case of autoimmune thrombocytopenia. Autoimmune pathologies were more associated with autoimmune chronic liver disease than other causes of chronic liver disease (47% vs 11.1%, p <0.001). Autoimmune pathologies were not statistically associated with female gender (p = 0.085) or young age (p = 0.483).Conclusion:In our study, the prevalence of autoimmune diseases during chronic liver diseases was 13.9%. This prevalence was higher in the case of autoimmune chronic liver diseases (47%), which would underline the importance of systematic screening for clinical and biological immune manifestations in those patients.Disclosure of Interests:None declared

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Serum Biomarkers of Liver Fibrosis Staging in the Era of the Concept “Compensated Advanced Chronic Liver Disease”

Journal of Clinical Medicine ◽

10.3390/jcm10153340 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3340

Author(s):

Koji Fujita ◽

Tsutomu Masaki

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Liver Diseases ◽

Serum Biomarkers ◽

Chronic Liver ◽

World Health ◽

Chronic Liver Diseases ◽

Fibrosis Staging ◽

Severe Fibrosis

Non-invasive indexes of liver fibrosis based on blood examinations have been developed for decades, partially replacing liver biopsy examinations. Recently, the concept of liver cirrhosis was revised and converted to “compensated advanced chronic liver diseases” since the Baveno VI consensus statement in 2015. The term “compensated advanced chronic liver diseases” was established based on the premise that serum biomarkers were not able to differentiate cirrhosis from severe fibrosis. The difficulty to histologically distinguish cirrhosis from severe fibrosis had been pointed out in 1977, when the definition and nomenclatures of cirrhosis had been determined by the World Health Organization. That was decades before serum biomarkers available at present were investigated. Though we are accustomed to differentiating the fibrosis stage as stage 1, 2, 3 (severe fibrosis), and 4 (cirrhosis), differentiation of cirrhosis from severe fibrosis is difficult even by histopathological examination. The current review will provide readers a framework to revise how to apply serum biomarkers on liver fibrosis staging in an era of the concept of “compensated advanced chronic liver disease”.

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Thrombin Generation in Chronic Liver Diseases—A Pilot Study

Healthcare ◽

10.3390/healthcare9050550 ◽

2021 ◽

Vol 9 (5) ◽

pp. 550

Author(s):

Liliana Vecerzan ◽

Ariela Olteanu ◽

Ionela Maniu ◽

Adrian Boicean ◽

Călin Remus Cipăian ◽

...

Keyword(s):

Liver Disease ◽

Pilot Study ◽

Chronic Liver Disease ◽

Liver Diseases ◽

Thrombin Generation ◽

Chronic Liver ◽

Control Group ◽

Coagulation Disorders ◽

Chronic Liver Diseases ◽

Control Subjects

The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The aim of this study was to analyze the parameters of thrombin generation in patients with chronic liver disease, as they are the most appropriate biomarkers to explore coagulation. (1) Background: The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The study of thrombin generation in patients with chronic liver disease provides a much more accurate assessment of the coagulation cascade; (2) Methods: This study is a prospective observational pilot study on hospitalized patients with chronic liver diseases that analyzed thrombin generation performed from their platelet-poor plasma versus that of control subjects. We analyzed a group of 59 patients with chronic liver disease and 62 control subjects; (3) Results: Thrombin generation was lower in hepatitis and cirrhosis patients compared to controls and decreases as the disease progressed. Lag time was higher in ethanolic etiology compared to the control group. Peak thrombin and endogenous thrombin potential were shorter in all etiologies when compared to the control group. The velocity index was significantly lower in HCV hepatopathies, ethanolic, and mixed etiology when compared with normal individuals; (4) Conclusions: Given the variability of thrombin generation in patients with chronic liver disease, its assay could serve to identify patients with high thrombotic and hemorrhagic risk and establish personalized conduct toward them.

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Medication Non-adherence Prevalence and Determinants in Children and Adolescents with Chronic Liver Diseases

Iranian Journal of Pediatrics ◽

10.5812/ijp.112323 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Seyed Mohsen Dehghani ◽

Alireza Shamsaeefar ◽

Azar Kazemi ◽

Kourosh Kazemi ◽

Amirali Mashhadiagha ◽

...

Keyword(s):

Logistic Regression ◽

Liver Disease ◽

Medication Adherence ◽

Chronic Liver Disease ◽

Liver Diseases ◽

Underlying Disease ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Housing Status ◽

Adherence Scale

Background: Medication adherence is one of the most important challenges in chronic diseases. Objectives: In this study, we investigated medication adherence prevalence among children with chronic liver diseases. Methods: A total of 160 children with chronic liver disease were enrolled in our study. We evaluated medication adherence using the 8-item Morisky Medication Adherence Scale (MMAS-8) and classified them based on the scores (score < 6 = low adherence, scores 6 - 8 = medium adherence, and > 8 = high adherence). Logistic regression recognized final influencing variables on adherence. Results: Of 160 patients, 84 (52.5%) were female, and the mean age of patients was 11.2 ± 4.4 years. Also, 56 participants (35%) were high adherers, and 66 (41.25%) were low adherers. The most common reason for low adherence was forgetfulness in 37 patients (23.13%) and low access to medication in 21 subjects (13.13%). In multivariate logistic regression, age, housing status, and underlying disease were significantly associated with medication adherence. Conclusions: Almost half of the children with liver cirrhosis demonstrated low medication adherence. Age, housing status, and underlying disease were significantly associated with medication adherence. We should implement programs to reduce medication non-adherence among children with chronic liver disease.

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The Role of the Gut Microbiome in Liver Fibrosis

10.20944/preprints202012.0041.v1 ◽

2020 ◽

Author(s):

Na Young Lee ◽

Ki Tae Suk

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Liver Fibrosis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Liver Diseases ◽

Sclerosing Cholangitis ◽

Chronic Liver ◽

Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, genetic conditions such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis, and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease from other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver cirrhosis.

Download Full-text