Animal models of chronic liver diseases

2013 ◽  
Vol 304 (5) ◽  
pp. G449-G468 ◽  
Author(s):  
Yan Liu ◽  
Christoph Meyer ◽  
Chengfu Xu ◽  
Honglei Weng ◽  
Claus Hellerbrand ◽  
...  
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
New Drugs ◽  
Limiting Factors ◽  
Rodent Models ◽  
Chronic Liver Diseases ◽  
Underlying Mechanisms

Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the “corresponding” human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases.

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

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.

scholarly journals Emerging Treatment Options for Sarcopenia in Chronic Liver Disease

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 250
Author(s):  
Yun Kim
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Behavioral Interventions ◽  
Liver Diseases ◽  
Treatment Options ◽  
Adverse Outcomes ◽  
Chronic Liver ◽  
Hormonal Changes ◽  
Chronic Liver Diseases ◽  
Underlying Mechanisms

Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.

scholarly journals Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1945
Author(s):  
Xianhui Zeng ◽  
Xianglei Yuan ◽  
Qiuyu Cai ◽  
Chengwei Tang ◽  
Jinhang Gao
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Regulation Of Gene Expression ◽  
Circular Rna ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Non Coding Rna ◽  
Epigenetic Regulator ◽  
Underlying Mechanisms

Circular RNA (circRNA) is a type of non-coding RNA characterized by a covalently closed continuous loop. CircRNA is generated by pre-mRNA through back-splicing and is probably cleared up by extracellular vesicles. CircRNAs play a pivotal role in the epigenetic regulation of gene expression at transcriptional and post-transcriptional levels. Recently, circRNAs have been demonstrated to be involved in the regulation of liver homeostasis and diseases. However, the epigenetic role and underlying mechanisms of circRNAs in chronic liver diseases remain unclear. This review discussed the role of circRNAs in non-neoplastic chronic liver diseases, including alcoholic liver disease (ALD), metabolic-associated fatty liver disease (MAFLD), viral hepatitis, liver injury and regeneration, liver cirrhosis, and autoimmune liver disease. The review also highlighted that further efforts are urgently needed to develop circRNAs as novel diagnostics and therapeutics for chronic liver diseases.

scholarly journals The Role of the Gut Microbiome in Liver Cirrhosis Treatment

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.

scholarly journals Asthenia and fatigue in hyperammonemia: etiopathogenesis and methods of correction

2022 ◽  
pp. 95-104
Author(s):  
E. Yu. Plotnikova ◽  
M. N. Sinkova ◽  
L. K. Isakov
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Signs And Symptoms ◽  
Chronic Liver ◽  
Blood Levels ◽  
Chronic Liver Diseases ◽  
Life Threatening ◽  
Underlying Causes ◽  
Principles Of Treatment ◽  
The Brain

Asthenia and fatigue are the most common syndromes in patients with liver disease, which significantly affects their quality of life. The prevalence of fatigue in chronic liver diseases is from 50% to 85%. While some progress has been made in understanding the processes that can cause fatigue in general, the underlying causes of fatigue associated with liver disease remain not well understood. In particular, many data suggest that fatigue associated with liver disease likely results from changes in neurotransmission in the brain against the background of hyperammonemia. Hyperammonemia is a metabolic state characterized by an increased level of  ammonia, a  nitrogen-containing compound. The  present review describes hyperammonemia, which is likely important in the pathogenesis of fatigue associated with liver disease. Ammonia is a potent neurotoxin, its elevated blood levels can cause neurological signs and symptoms that can be acute or chronic, depending on the  underlying pathology. Hyperammonemia should be recognized early, and immediately treated to prevent the development of life-threatening complications, such as, swelling of the brain and coma. The article gives pathophysiological mechanisms of influence of hyperammonemia on state of psychovegetative status of patients with liver diseases, also lists basic principles of treatment. A significant part of the article is devoted to L-ornithine-L-aspartate, which is effective in asthenia and fatigue to reduce the level of hyperammonemia through a variety of well-studied mechanisms in chronic liver diseases.

scholarly journals The Course Of Chronic Liver Disease In Patients With Covid-2019 (Literature Review And Own Data)

2021 ◽  
Vol 03 (09) ◽  
pp. 69-74
Author(s):  
Muxamedova Z.R. ◽  
Keyword(s):  
Liver Disease ◽  
Literature Review ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Biochemical Activity ◽  
Severe Liver ◽  
Risk Of Mortality ◽  
The World ◽  
Severe Liver Damage

The pandemic of the new coronavirus COVID-19 has switched medicine around the world on the primary fight against this infection. Patients with chronic liver diseases require increased attention of doctors during an epidemic, since against the background of an exacerbation of their disease, not only the risk of contracting the COVID 19 viral infection increases, but also its more severe course. Patients with confirmed COVID-19 with severe liver damage - high biochemical activity. According to some reports, patients with a severe course of COVID-19 have an increase in ALT levels, a decrease in the number of platelets, a decrease in the level of albumin, and a connection (although not all indicators) with a higher risk of mortality is possible.

scholarly journals Patients with chronic liver disease and COVID-19 (literature review and own data)

2021 ◽  
Vol 2 (2/S) ◽  
pp. 498-503
Author(s):  
D.H. Yuldasheva ◽  
Z.X. Muxamedova ◽  
N.S. Shadjanova
Keyword(s):  
Liver Disease ◽  
Literature Review ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Biochemical Activity ◽  
Severe Liver ◽  
Risk Of Mortality ◽  
The World ◽  
Severe Liver Damage

The pandemic of the new coronavirus COVID-19 has switched medicine around the world on the primary fight against this infection. Patients with chronic liver diseases require increased attention of doctors during an epidemic, since against the background of an exacerbation of their disease, not only the risk of contracting the COVID 19 viral infection increases, but also its more severe course. Patients with confirmed COVID-19 with severe liver damage - high biochemical activity. According to some reports, patients with a severe course of COVID-19 have an increase in ALT levels, a decrease in the number of platelets, a decrease in the level of albumin, and a connection (although not all indicators) with a higher risk of mortality is possible.

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.

Effects of chronic liver diseases on mitochondrial DNA transcription and replication in human liver

Life Sciences ◽  
1999 ◽  
Vol 65 (5) ◽  
pp. 557-563 ◽  
Author(s):  
Katsuhiro Kotake ◽  
Toshiaki Nonami ◽  
Tsuyoshi Kurokawa ◽  
Akimasa Nakao ◽  
Taro Murakami ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Dna Transcription ◽  
Transcription And Replication
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