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Clinics and Research in Hepatology and... Sep 2015Liver fibrosis is a serious health problem worldwide, which can be induced by a wide spectrum of chronic liver injuries. However, until today, there is no effective... (Review)
Review
Liver fibrosis is a serious health problem worldwide, which can be induced by a wide spectrum of chronic liver injuries. However, until today, there is no effective therapy available for liver fibrosis except the removal of underlying etiology or liver transplantation. Recent studies indicate that liver fibrosis is reversible when the causative agent(s) is removed. Understanding of mechanisms of liver fibrosis regression will lead to the identification of new therapeutic targets for liver fibrosis. This review summarizes recent research progress on mechanisms of reversibility of liver fibrosis. While most of the research has been focused on HSCs/myofibroblasts and inflammatory pathways, the crosstalk between different organs, various cell types and multiple signaling pathways should not be overlooked. Future studies that lead to fully understanding of the crosstalk between different cell types and the molecular mechanism underlying the reversibility of liver fibrosis will definitely give rise to new therapeutic strategies to treat liver fibrosis.
Topics: Extracellular Matrix; Humans; Liver Cirrhosis; Macrophages; Myofibroblasts; Remission Induction
PubMed: 26206574
DOI: 10.1016/j.clinre.2015.06.015 -
Translational Research : the Journal of... Dec 2019Liver fibrosis is a wound-healing process induced by chronic liver injuries, such as nonalcoholic steatohepatitis, hepatitis, alcohol abuse, and metal poisoning. The... (Review)
Review
Liver fibrosis is a wound-healing process induced by chronic liver injuries, such as nonalcoholic steatohepatitis, hepatitis, alcohol abuse, and metal poisoning. The accumulation of excessive extracellular matrix (ECM) in the liver is a key characteristic of liver fibrosis. Activated hepatic stellate cells (HSCs) are the major producers of ECM and therefore play irreplaceably important roles during the progression of liver fibrosis. Liver fibrogenesis is highly correlated with the activation of HSCs, which is regulated by numerous profibrotic cytokines. Using RNA interference to downregulate these cytokines in activated HSCs is a promising strategy to reverse liver fibrosis. Meanwhile, microRNAs (miRNAs) have also been exploited for the treatment of liver fibrosis. This review focuses on the current siRNA- and miRNA-based liver fibrosis treatment strategies by targeting activated HSCs in the liver.
Topics: Animals; Humans; Liver Cirrhosis; MicroRNAs; Models, Biological; RNA, Small Interfering; Signal Transduction
PubMed: 31476281
DOI: 10.1016/j.trsl.2019.07.007 -
Journal of Translational Medicine May 2021Liver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular... (Review)
Review
Liver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.
Topics: Carcinoma, Hepatocellular; Fibrosis; Humans; Hypoxia; Liver; Liver Cirrhosis; Liver Neoplasms; Quality of Life
PubMed: 33933107
DOI: 10.1186/s12967-021-02854-x -
Radiologia 2018There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis... (Review)
Review
There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers' measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems.
Topics: Biomarkers; Elasticity Imaging Techniques; Humans; Liver Cirrhosis; Magnetic Resonance Imaging
PubMed: 29108657
DOI: 10.1016/j.rx.2017.09.003 -
Annals of Hepatology 2017Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most... (Review)
Review
Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.
Topics: Animals; Anti-Inflammatory Agents; Cell Communication; Cytokines; Disease Progression; Hepatic Stellate Cells; Hepatocytes; Humans; Inflammation Mediators; Liver; Liver Cirrhosis; Signal Transduction; Time Factors; Treatment Outcome
PubMed: 28051792
DOI: 10.5604/16652681.1226814 -
International Journal of Molecular... Feb 2020Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a... (Review)
Review
Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In the development of liver fibrosis, some lncRNAs regulate diverse cellular processes by acting as competing endogenous RNAs (ceRNAs) and binding proteins. Previous investigations demonstrated that overexpression of lncRNAs such as H19, maternally expressed gene 3 (MEG3), growth arrest-specific transcript 5 (GAS5), Gm5091, NR_002155.1, and HIF 1alpha-antisense RNA 1 (HIF1A-AS1) can inhibit the progression of liver fibrosis. Furthermore, the upregulation of several lncRNAs [e.g., nuclear paraspeckle assembly transcript 1 (NEAT1), hox transcript antisense RNA (Hotair), and liver-enriched fibrosis-associated lncRNA1 (lnc-LFAR1)] has been reported to promote liver fibrosis. This review will focus on the functions and mechanisms of lncRNAs, the lncRNA transcriptome profile of liver fibrosis, and the main lncRNAs involved in the signalling pathways that regulate hepatic fibrosis. This review provides insight into the screening of therapeutic and diagnostic markers of liver fibrosis.
Topics: Animals; Biomarkers; Gene Expression Regulation; Humans; Liver; Liver Cirrhosis; RNA, Long Noncoding; Signal Transduction; Transcriptome
PubMed: 32098245
DOI: 10.3390/ijms21041482 -
PeerJ 2022Liver fibrosis develops as a result of severe liver damage and is considered a major clinical concern throughout the world. Many factors are crucial for liver fibrosis... (Review)
Review
Liver fibrosis develops as a result of severe liver damage and is considered a major clinical concern throughout the world. Many factors are crucial for liver fibrosis progression. While advancements have been made to understand this disease, no effective pharmacological drug and treatment strategies have been established that can effectively prevent liver fibrosis or even could halt the fibrotic process. Most of those advances in curing liver fibrosis have been aimed towards mitigating the causes of fibrosis, including the development of potent antivirals to inhibit the hepatitis virus. It is not practicable for many individuals; however, a liver transplant becomes the only suitable alternative. A liver transplant is an expensive procedure. Thus, there is a significant need to identify potential targets of liver fibrosis and the development of such agents that can effectively treat or reverse liver fibrosis by targeting them. Researchers have identified hypoxia-inducible factors (HIFs) in the last 16 years as important transcription factors driving several facets of liver fibrosis, making them possible therapeutic targets. The latest knowledge on HIFs and their possible role in liver fibrosis, along with the cell-specific activities of such transcription factors that how they play role in liver fibrosis progression, is discussed in this review.
Topics: Humans; Cell Hypoxia; Hypoxia; Liver Cirrhosis; Liver Diseases; Transcription Factors
PubMed: 36523459
DOI: 10.7717/peerj.14299 -
International Journal of Molecular... Jul 2021Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver... (Review)
Review
Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called "exosomes" have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.
Topics: Animals; Biomarkers; Cholangitis, Sclerosing; Circulating MicroRNA; Epigenesis, Genetic; Exosomes; Fatty Liver, Alcoholic; Gene Expression Regulation; Hepatitis, Autoimmune; Humans; Liver Cirrhosis; Liver Cirrhosis, Biliary; Non-alcoholic Fatty Liver Disease
PubMed: 34360904
DOI: 10.3390/ijms22158139 -
World Journal of Gastroenterology May 2015Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy. If the etiology cannot be eliminated, liver fibrosis progresses to... (Review)
Review
Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy. If the etiology cannot be eliminated, liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy; both are associated with a fatal outcome. Liver transplantation, the only curative therapy, is still mostly unavailable. Liver fibrosis was shown to be a reversible process; however, complete reversibility remains debatable. Recently, the molecular markers of liver fibrosis were shown to be transmitted across generations. Epigenetic mechanisms including DNA methylation, histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis. Furthermore, epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations. However, the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated. This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers. The fact that epigenetic changes, unlike genetic mutations, are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis, to prevent the development of malignancy and to regulate heritability of fibrosis phenotype.
Topics: Animals; Biomedical Research; DNA Methylation; Epigenesis, Genetic; Genetic Markers; Genetic Predisposition to Disease; Heredity; Histones; Humans; Liver Cirrhosis; Pedigree; Phenotype; Prognosis; Protein Processing, Post-Translational; RNA, Untranslated; Risk Factors
PubMed: 25954087
DOI: 10.3748/wjg.v21.i17.5138 -
BMJ (Clinical Research Ed.) Sep 1992
Topics: Child; Humans; Liver Cirrhosis
PubMed: 1393030
DOI: 10.1136/bmj.305.6853.537