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Gene Expression Apr 2019The term blood-bile barrier (BBlB) refers to the physical structure within a hepatic lobule that compartmentalizes and hence segregates sinusoidal blood from canalicular... (Review)
Review
The term blood-bile barrier (BBlB) refers to the physical structure within a hepatic lobule that compartmentalizes and hence segregates sinusoidal blood from canalicular bile. Thus, this barrier provides physiological protection in the liver, shielding the hepatocytes from bile toxicity and restricting the mixing of blood and bile. BBlB is primarily composed of tight junctions; however, adherens junction, desmosomes, gap junctions, and hepatocyte bile transporters also contribute to the barrier function of the BBlB. Recent findings also suggest that disruption of BBlB is associated with major hepatic diseases characterized by cholestasis and aberrations in BBlB thus may be a hallmark of many chronic liver diseases. Several molecular signaling pathways have now been shown to play a role in regulating the structure and function and eventually contribute to regulation of the BBlB function within the liver. In this review, we will discuss the structure and function of the BBlB, summarize the methods to assess the integrity and function of BBlB, discuss the role of BBlB in liver pathophysiology, and finally, discuss the mechanisms of BBlB regulation. Collectively, this review will demonstrate the significance of the BBlB in both liver homeostasis and hepatic dysfunction.
Topics: Animals; Bile Canaliculi; Blood Vessels; Hepatocytes; Humans; Intercellular Junctions; Liver; Liver Diseases
PubMed: 30646969
DOI: 10.3727/105221619X15469715711907 -
Cells Jun 2023Fibrosis is an unavoidable consequence of chronic inflammation. Extracellular matrix deposition by fibroblasts, stimulated by multiple pathways, is the first step in the... (Review)
Review
Fibrosis is an unavoidable consequence of chronic inflammation. Extracellular matrix deposition by fibroblasts, stimulated by multiple pathways, is the first step in the onset of chronic liver disease, and its propagation promotes liver dysfunction. At the same time, chronic liver disease is characterized by alterations in primary and secondary hemostasis but unlike previously thought, these changes are not associated with an increased risk of bleeding complications. In recent years, the role of coagulation imbalance has been postulated as one of the main mechanisms promoting hepatic fibrogenesis. In this review, we aim to investigate the function of microvascular thrombosis in the progression of liver disease and highlight the molecular and cellular networks linking hemostasis to fibrosis in this context. We analyze the predictive and prognostic role of coagulation products as biomarkers of liver decompensation (ascites, variceal hemorrhage, and hepatic encephalopathy) and liver-related mortality. Finally, we evaluate the current evidence on the application of antiplatelet and anticoagulant therapies for prophylaxis of hepatic decompensation or prevention of the progression of liver fibrosis.
Topics: Humans; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Liver Cirrhosis; Liver Diseases; Thrombosis
PubMed: 37443746
DOI: 10.3390/cells12131712 -
British Journal of Pharmacology Jul 2022Liver diseases are the fourth common death in Europe responsible for about 2 million death per year worldwide. Among the known detrimental causes for liver dysfunction... (Review)
Review
Liver diseases are the fourth common death in Europe responsible for about 2 million death per year worldwide. Among the known detrimental causes for liver dysfunction are virus infections, intoxications and obesity. The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor activated by aldosterone or glucocorticoids but also by pathological milieu factors. Canonical actions of the MR take place in epithelial cells of kidney, colon and sweat glands and contribute to sodium reabsorption, potassium secretion and extracellular volume homeostasis. The non-canonical functions can be initiated by inflammation or an altered micro-milieu leading to fibrosis, hypertrophy and remodelling in various tissues. This narrative review summarizes the evidence regarding the role of MR in portal hypertension, non-alcoholic fatty liver disease, liver fibrosis and cirrhosis, demonstrating that inhibition of the MR in vivo seems to be beneficial for liver function and not just for volume regulation. Unfortunately, the underlying molecular mechanisms are still not completely understood. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.
Topics: Aldosterone; Fibrosis; Homeostasis; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Receptors, Mineralocorticoid
PubMed: 34935140
DOI: 10.1111/bph.15784 -
Pathology Oncology Research : POR Apr 2020Liver diseases such as liver cirrhosis, primary and metastatic liver cancers are still a major medical challenge. Syndecan-1 is one of the most important proteoglycans...
Liver diseases such as liver cirrhosis, primary and metastatic liver cancers are still a major medical challenge. Syndecan-1 is one of the most important proteoglycans in the liver. Syndecan-1 is normally expressed on the surfaces of hepatocytes and cholangiocytes. Due to liver diseases the amount of syndecan-1 increases in the liver. Despite the emerging data of the biological function of syndecan-1, the clinical usefulness of this proteoglycan is still unknown. In our study we correlated syndecan-1 expression to clinico-pathological data. We found that syndecan-1 proved to be a good marker for hepatitis C virus based hepatocellular carcinoma and increased with liver dysfunction.
Topics: Humans; Liver Diseases; Syndecan-1
PubMed: 30826971
DOI: 10.1007/s12253-019-00617-0 -
BioTechniques Nov 2021SERPINA4/kallistatin is a multifunctional protein expressed from the liver; its concentration in blood circulation reflects the degree of liver dysfunction and may...
SERPINA4/kallistatin is a multifunctional protein expressed from the liver; its concentration in blood circulation reflects the degree of liver dysfunction and may serve as a diagnostic/prognostic biomarker for chronic liver diseases (CLD). Antibodies specific for SERPINA4/kallistatin were used for the development of an enzyme-linked immunosorbent assay (ELISA). For correlative studies, blood samples from patients with cirrhotic liver and healthy patients were collected from R.L. Jalappa Hospital & Research Centre, Kolar. Interference of other SERPINs was ruled out using western blot analysis. Quantitative ELISA was developed using monospecific antibodies as capture antibodies. The accuracy of the developed ELISA was determined by inter- and intra-assay precision. Linearity was defined using a spiked sample with serial dilutions. Reduced levels of SERPINA4/kallistatin were observed in patients with CLD compared with healthy controls.
Topics: Biomarkers; Blotting, Western; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Humans; Liver; Liver Diseases; Serpins
PubMed: 34528838
DOI: 10.2144/btn-2018-0194 -
World Journal of Gastroenterology Nov 2021Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a "rebalanced hemostasis", which can easily be tipped toward... (Review)
Review
Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a "rebalanced hemostasis", which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Hemostasis; Humans; Liver Diseases; Thrombelastography
PubMed: 34876789
DOI: 10.3748/wjg.v27.i42.7285 -
Cells Mar 2022Over the last few years, the number of research publications about the role of catecholamines (epinephrine, norepinephrine, and dopamine) in the development of liver... (Review)
Review
Over the last few years, the number of research publications about the role of catecholamines (epinephrine, norepinephrine, and dopamine) in the development of liver diseases such as liver fibrosis, fatty liver diseases, or liver cancers is constantly increasing. However, the mechanisms involved in these effects are not well understood. In this review, we first recapitulate the way the liver is in contact with catecholamines and consider liver implications in their metabolism. A focus on the expression of the adrenergic and dopaminergic receptors by the liver cells is also discussed. Involvement of catecholamines in physiological (glucose metabolism, lipids metabolism, and liver regeneration) and pathophysiological (impact on drug-metabolizing enzymes expression, liver dysfunction during sepsis, fibrosis development, or liver fatty diseases and liver cancers) processes are then discussed. This review highlights the importance of understanding the mechanisms through which catecholamines influence liver functions in order to draw benefit from the adrenergic and dopaminergic antagonists currently marketed. Indeed, as these molecules are well-known drugs, their use as therapies or adjuvant treatments in several liver diseases could be facilitated.
Topics: Adrenergic Agents; Catecholamines; Humans; Liver Neoplasms; Norepinephrine
PubMed: 35326472
DOI: 10.3390/cells11061021 -
International Reviews of Immunology 2014Despite the progress made in the clinical management of sepsis, sepsis morbidity and mortality rates remain high. The inflammatory pathogenesis and organ injury leading... (Review)
Review
Despite the progress made in the clinical management of sepsis, sepsis morbidity and mortality rates remain high. The inflammatory pathogenesis and organ injury leading to death from sepsis are not fully understood for vital organs, especially the liver. Only recently has the role of the liver in sepsis begun to be revealed. Pre-existing liver dysfunction is a risk factor for the progression of infection to sepsis. Liver dysfunction after sepsis is an independent risk factor for multiple organ dysfunction and sepsis-induced death. The liver works as a lymphoid organ in response to sepsis. Acting as a double-edged sword in sepsis, the liver-mediated immune response is responsible for clearing bacteria and toxins but also causes inflammation, immunosuppression, and organ damage. Attenuating liver injury and restoring liver function lowers morbidity and mortality rates in patients with sepsis. This review summarizes the central role of liver in the host immune response to sepsis and in clinical outcomes.
Topics: Animals; Humans; Liver; Liver Diseases; Multiple Organ Failure; Outcome Assessment, Health Care; Risk; Sepsis
PubMed: 24611785
DOI: 10.3109/08830185.2014.889129 -
Current Opinion in General Surgery 1993From more than 900 articles in the medical literature, published between August 1, 1991 and July 31, 1992, 46 were selected for review. During the year of review, major... (Review)
Review
From more than 900 articles in the medical literature, published between August 1, 1991 and July 31, 1992, 46 were selected for review. During the year of review, major international symposiums were held on a new drug, FK506, and intestinal transplantation. In addition, at least one new attempt at a unifying hypothesis regarding graft adaptation was proposed. Other studies included living related donor transplantation, results with transplantation for alcoholics, and the controversy regarding the role of liver transplantation for the treatment of Budd-Chiari syndrome. Concerns regarding the recurrence of both hepatitis and primary hepatic malignancy following liver transplantation were also addressed. Two innovative approaches to the treatment of acute liver failure offer exciting promise for the future. Other subjects include histologic evaluation of renal dysfunction in patients with liver disease, quality of life after transplantation, and the proper distribution of precious donor livers.
Topics: Adult; Child; Graft Rejection; Humans; Immunosuppression Therapy; Liver Diseases; Liver Neoplasms; Liver Transplantation; Organ Preservation; Postoperative Complications
PubMed: 7583980
DOI: No ID Found -
Indian Journal of Pathology &... 2022Liver transplantation is now a well-established therapeutic strategy for irreversible acute and chronic liver diseases. There is a broad spectrum of complications... (Review)
Review
Liver transplantation is now a well-established therapeutic strategy for irreversible acute and chronic liver diseases. There is a broad spectrum of complications encountered in early and late period after transplantation and these contribute to significant morbidity and mortality. Distinguishing among these complications often requires interpretation of allograft biopsies. Histology is the gold standard for the diagnosis of rejection. However, interpretation of these biopsies is quite challenging due to the atypical and complex histomorphology. Multiple simultaneous insults, effects of immunosuppression (IMS), de novo complications, and presentations distinct from non-transplant setting are a few cardinal concerns. Awareness of the time period of occurrence of various complications, the most characteristic histological features or patterns, and distinguishing features between various complications are crucial. The management can be completely divergent; hence, recognition of dominant problem and interpretation in appropriate clinical context is much needed. This review focuses on histopathology of major complications accountable for early and late graft dysfunction. Tabulation of clinico-pathological features to distinguish various complications helps to solve the conundrums and arrive at the correct diagnosis.
Topics: Biopsy; Graft Rejection; Humans; Liver; Liver Diseases; Liver Transplantation
PubMed: 35435355
DOI: 10.4103/ijpm.ijpm_1090_21