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Molecular Aspects of Medicine Feb 2019The progression of chronic liver diseases (CLD), irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response as well as... (Review)
Review
The progression of chronic liver diseases (CLD), irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response as well as sustained activation of liver fibrogenesis and wound healing response. Liver fibrogenesis, is a dynamic, highly integrated molecular, cellular and tissue process responsible for driving the excess accumulation of extracellular matrix (ECM) components (i.e., liver fibrosis) sustained by an eterogeneous population of hepatic myofibroblasts (MFs). The process of liver fibrogenesis recognizes a number of common and etiology-independent mechanisms and events but it is also significantly influenced by the specific etiology, as also reflected by peculiar morphological patterns of liver fibrosis development. In this review we will analyze the most relevant established and/or emerging pathophysiological issues underlying CLD progression with a focus on the role of critical hepatic cell populations, mechanisms and signaling pathways involved, as they represent potential therapeutic targets, to finally analyze selected and relevant clinical issues.
Topics: Animals; Biomarkers; Cellular Microenvironment; Chronic Disease; Disease Progression; Disease Susceptibility; Energy Metabolism; Extracellular Matrix; Gene Expression Regulation; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Liver Diseases; Myofibroblasts; Signal Transduction
PubMed: 30213667
DOI: 10.1016/j.mam.2018.09.002 -
The American Journal of Gastroenterology Feb 2018Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most...
Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol withdrawal syndrome, surveillance for infections and early effective antibiotic therapy, nutritional supplementation, and treatment of the underlying alcohol-use disorder. Liver transplantation, a definitive treatment option in patients with advanced alcoholic cirrhosis, may also be considered in selected patients with AH cases, who do not respond to medical therapy. There is a clinical unmet need to develop more effective and safer therapies for patients with ALD.
Topics: Alcohol Withdrawal Delirium; Alcoholism; Hepatitis, Alcoholic; Humans; Liver Diseases, Alcoholic; Liver Transplantation; Prognosis
PubMed: 29336434
DOI: 10.1038/ajg.2017.469 -
Cellular & Molecular Immunology Jan 2021The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ... (Review)
Review
The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota. The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens. Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases. Of immense importance is the step from high-throughput sequencing (correlation) to mechanistic studies (causality) and therapeutic intervention. Here, we review the gut microbiota, liver immunology, and the interaction between the gut and liver. In addition, the impairment in the gut-liver axis found in various liver diseases is reviewed here, with an emphasis on alcohol-associated liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and autoimmune liver disease (AILD). On the basis of growing evidence from these preclinical studies, we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.
Topics: Animals; Gastrointestinal Microbiome; Humans; Liver; Liver Diseases
PubMed: 33318628
DOI: 10.1038/s41423-020-00592-6 -
International Journal of Molecular... May 2021Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes... (Review)
Review
Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.
Topics: Alcohol Drinking; Animals; Humans; Liver Diseases, Alcoholic; Risk Factors
PubMed: 34068269
DOI: 10.3390/ijms22105170 -
Nutrients Dec 2017Malnutrition in children and adults with advanced liver disease represents a tremendous challenge as the nutritional problems are multifactorial. This Editorial comments...
Malnutrition in children and adults with advanced liver disease represents a tremendous challenge as the nutritional problems are multifactorial. This Editorial comments the articles appearing in this special issue of , "Nutrition and Liver disease" dealing with multiple diagnostic and therapeutic features that relate the outcomes of liver disease to nutrition. To improve quality of life and prevent nutrition-related medical complications, patients diagnosed with advanced liver disease should have their nutritional status promptly assessed and be supported by appropriate dietary interventions. Furthermore specific food supplements and/or restriction diets are often necessary for those with hepatic conditions associated with an underlying metabolic or nutritional or intestinal disease.
Topics: Body Composition; Humans; Liver Diseases; Malnutrition; Nutrition Assessment; Nutritional Status; Nutritional Support; Prognosis; Risk Factors
PubMed: 29295475
DOI: 10.3390/nu10010009 -
Hepatology (Baltimore, Md.) Apr 2023The syndemic of hazardous alcohol consumption, opioid use, and obesity has led to important changes in liver disease epidemiology that have exacerbated health... (Review)
Review
The syndemic of hazardous alcohol consumption, opioid use, and obesity has led to important changes in liver disease epidemiology that have exacerbated health disparities. Health disparities occur when plausibly avoidable health differences are experienced by socially disadvantaged populations. Highlighting health disparities, their sources, and consequences in chronic liver disease is fundamental to improving liver health outcomes. There have been large increases in alcohol use disorder in women, racial and ethnic minorities, and those experiencing poverty in the context of poor access to alcohol treatment, leading to increasing rates of alcohol-associated liver diseases. Rising rates of NAFLD and associated fibrosis have been observed in Hispanic persons, women aged > 50, and individuals experiencing food insecurity. Access to viral hepatitis screening and linkage to treatment are suboptimal for racial and ethnic minorities and individuals who are uninsured or underinsured, resulting in greater liver-related mortality and later-stage diagnoses of HCC. Data from more diverse cohorts on autoimmune and cholestatic liver diseases are lacking, supporting the need to study the contemporary epidemiology of these disorders in greater detail. Herein, we review the existing literature on racial and ethnic, gender, and socioeconomic disparities in chronic liver diseases using a social determinants of health framework to better understand how social and structural factors cause health disparities and affect chronic liver disease outcomes. We also propose potential solutions to eliminate disparities, outlining health-policy, health-system, community, and individual solutions to promote equity and improve health outcomes.
Topics: Female; Humans; Alcohol Drinking; Carcinoma, Hepatocellular; Healthcare Disparities; Hispanic or Latino; Liver Diseases, Alcoholic; Liver Neoplasms; Racial Groups; United States; Health Status Disparities; Middle Aged
PubMed: 35993341
DOI: 10.1002/hep.32743 -
Hepatology (Baltimore, Md.) Dec 2014Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]),... (Review)
Review
Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China.
Topics: China; Gastroenterology; Humans; Liver Diseases; Liver Transplantation; Medicine, Chinese Traditional
PubMed: 25164003
DOI: 10.1002/hep.27406 -
Frontiers in Immunology 2019Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited... (Review)
Review
Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited macrophages derived from peritoneal cavity as well as the bone marrow. KCs are located in the liver sinusoid where they scavenge the microbe from the portal vein to maintain liver homeostasis. Liver injury may trigger hepatic recruitment of peritoneal macrophages and monocyte-derived macrophages. Studies describing macrophage accumulation have shown that hepatic macrophages are involved in the initiation and progression of various liver diseases. They act as tolerogenic antigen-presenting cells to inhibit T-cell activation by producing distinct sets of cytokines, chemokines, and mediators to maintain or resolve inflammation. Furthermore, by releasing regenerative growth factors, matrix metalloproteinase arginase, they promote tissue repair. Recent experiments found that KCs and recruited macrophages may play different roles in the development of liver disease. Given that hepatic macrophages are considerably plastic populations, their phenotypes and functions are likely switching along disease progression. In this review, we summarize current knowledge about the role of tissue-resident macrophages and recruited macrophages in pathogenesis of alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), viral hepatitis, and hepatocellular carcinoma (HCC).
Topics: Biomarkers; Cell Communication; Cytokines; Disease Management; Disease Susceptibility; Humans; Immunophenotyping; Kupffer Cells; Liver Diseases; Macrophages; Molecular Targeted Therapy; Phenotype
PubMed: 32047496
DOI: 10.3389/fimmu.2019.03112 -
Cell Host & Microbe Aug 2020The liver communicates with the intestine via the portal vein, biliary system, and mediators in the circulation. Microbes in the intestine maintain liver homeostasis but... (Review)
Review
The liver communicates with the intestine via the portal vein, biliary system, and mediators in the circulation. Microbes in the intestine maintain liver homeostasis but can also serve as a source of pathogens and molecules that contribute to fatty liver diseases. We review changes in the gut microbiota that can promote development or progression of alcohol-associated and non-alcoholic fatty liver disease-the most common chronic liver diseases in Western countries. We discuss how microbes and their products contribute to liver disease pathogenesis, putative microbial biomarkers of disease, and potential treatment approaches based on manipulation of the gut microbiota. Increasing our understanding of interactions between the intestinal microbiome and liver might help us identify patients with specific disease subtypes and select specific microbiota-based therapies.
Topics: Animals; Dysbiosis; Fatty Liver, Alcoholic; Gastrointestinal Microbiome; Host Microbial Interactions; Humans; Intestines; Liver; Mice; Non-alcoholic Fatty Liver Disease; Probiotics
PubMed: 32791115
DOI: 10.1016/j.chom.2020.07.007 -
Journal of Hepatology Oct 2015Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal... (Review)
Review
Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.
Topics: Hepatocytes; Humans; Liver Diseases; Phenotype; Tight Junctions
PubMed: 26116792
DOI: 10.1016/j.jhep.2015.06.015