scholarly journals Liver Disease and Hemostasis (Review) Part 2. Cholestatic Liver Disease and Hemostasis

2019 ◽  
Vol 15 (6) ◽  
pp. 80-93 ◽  
Author(s):  
Vasiliy I. Reshetnyak ◽  
Igor V. Maev ◽  
Tatiana M. Reshetnyak ◽  
Sergei V. Zhuravel ◽  
Vladimir M. Pisarev
Keyword(s):  
Liver Disease ◽  
Critical Illness ◽  
Liver Diseases ◽  
Multiorgan Failure ◽  
Phospholipid Composition ◽  
Current Data ◽  
Coagulation System ◽  
Cholestatic Liver Disease ◽  
Liver Disorders ◽  
Hemostatic Disorders

The presence or development of liver disorders can significantly complicate the course of critical illness and terminal conditions. Systemic hemostatic disorders are common in Intensive Care Units patients with cholestatic liver diseases, so the study of the mechanisms of their development can contribute to the understanding of the development of multiorgan failure in critical illness.The review discusses current data on changes in hemostatic parameters in patients with cholestatic liver diseases, proposes a mechanism for the development of such disorders, which involve interactions of phospholipids with platelet and endotheliocyte membranes. It is suggested that a trend for thrombosis in patients with cholestatic liver disease is due to increased accumulation of bile acids in the systemic circulation. Available data demonstrate that the antiphospholipid syndrome may predispose to the formation of blood clots due to alterations of phospholipid composition of membranes of platelets and vascular endothelial cells by circulating antiphospholipid antibodies. Clarifying the mechanisms contributing to changes of the blood coagulation system parameters in liver disorders will aid to development of optimal correction of hemostatic disorders in patients with chronic liver diseases.

scholarly journals Cell Death in Liver Diseases: A Review

2020 ◽  
Vol 21 (24) ◽  
pp. 9682
Author(s):  
Layla Shojaie ◽  
Andrea Iorga ◽  
Lily Dara
Keyword(s):  
Cell Death ◽  
Liver Disease ◽  
Liver Injury ◽  
Liver Diseases ◽  
Disease Model ◽  
Current Data ◽  
Critical Event ◽  
Cholestatic Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Cell Death Pathway

Regulated cell death (RCD) is pivotal in directing the severity and outcome of liver injury. Hepatocyte cell death is a critical event in the progression of liver disease due to resultant inflammation leading to fibrosis. Apoptosis, necrosis, necroptosis, autophagy, and recently, pyroptosis and ferroptosis, have all been investigated in the pathogenesis of various liver diseases. These cell death subroutines display distinct features, while sharing many similar characteristics with considerable overlap and crosstalk. Multiple types of cell death modes can likely coexist, and the death of different liver cell populations may contribute to liver injury in each type of disease. This review addresses the known signaling cascades in each cell death pathway and its implications in liver disease. In this review, we describe the common findings in each disease model, as well as the controversies and the limitations of current data with a particular focus on cell death-related research in humans and in rodent models of alcoholic liver disease, non-alcoholic fatty liver disease and steatohepatitis (NASH/NAFLD), acetaminophen (APAP)-induced hepatotoxicity, autoimmune hepatitis, cholestatic liver disease, and viral hepatitis.

scholarly journals Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model

2021 ◽  
Vol 22 (15) ◽  
pp. 8253
Author(s):  
Jung-Yeon Kim ◽  
Yongmin Choi ◽  
Jaechan Leem ◽  
Jeong Eun Song
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Heme Oxygenase ◽  
Murine Model ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Heme Oxygenase 1 ◽  
Cholestatic Liver Disease ◽  
Hepatocyte Apoptosis ◽  
Cobalt Protoporphyrin

Cholestatic liver diseases can progress to end-stage liver disease and reduce patients’ quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-β pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.

Primary Biliary Cirrhosis

2015 ◽  
Author(s):  
Daniel S. Pratt ◽  
Lindsay Y. King
Keyword(s):  
Differential Diagnosis ◽  
Liver Disease ◽  
Primary Biliary Cirrhosis ◽  
Liver Diseases ◽  
American Association ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Common Cause ◽  
History Of

Primary biliary cirrhosis (PBC) is a progressive autoimmune disease of the liver. It is the most common cause of chronic intrahepatic cholestatic liver disease in adults. This review addresses the epidemiology, etiology and genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, complications, and prognosis of PBC. Figures show the pathogenesis and natural history of PBC and histologic features of the four stages of PBC. Tables list diagnostic criteria for PBC via the American Association for the Study of Liver Diseases, differential diagnosis for PBC, medications used to treat PBC, secondary therapy for PBC, and follow-up of patients with PBC. This review contains 2 highly rendered figures, 5 tables, and 45 references.

Saponins in management of Hepatic Disorders: a review

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasmine Chaudhary ◽  
Akash Jain ◽  
Randhir Dahiya
Keyword(s):  
Liver Disease ◽  
Side Effects ◽  
Liver Diseases ◽  
Hepatoprotective Activity ◽  
Herbal Drugs ◽  
Cost Of Treatment ◽  
Liver Disorders ◽  
Underlying Mechanisms ◽  
Major Factors ◽  
The Cost

: Liver disease is one of the major factors responsible for increased morbidity and mortality worldwide. Presently, limited therapeutic options are available to treat liver diseases. Moreover, allopathic medications are a double-edged sword due to their unfavorable side effects and exaggerated cost of therapy associated with the treatment. Transplantation of the liver is still in infancy state and is associated with staggering cost as well as non-accessibility of donors. Moreover, the cost of treatment is also a very significant hindrance in the treatment of liver disorders. Therefore, the focus is shifting to evaluate the potential of herbal drugs for the management of liver disorders. Although the course of treatment with the herbals is slow yet, the effects are more promising due to lesser side effects and reduced cost of therapy. Numerous plants have been reported to possess hepatoprotective activity due to the presence of phytochemicals like alkaloids, flavonoids, saponins, etc. Among these phytoconstituents, saponins are considered more promising candidates in the management of hepatic disorders. The present review is focused on the plants containing saponins used in the management of hepatic disorders with their underlying mechanisms.

Liver disorders

2016 ◽  
Author(s):  
Chris Verslype ◽  
David Cassiman ◽  
Johan Verhaeghe
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Liver Failure ◽  
Liver Diseases ◽  
Systematic Approach ◽  
Liver Disorders ◽  
Diagnostic Characteristics ◽  
Mother And Child ◽  
Prognostic Implications ◽  
In Pregnancy

Liver disease can complicate 5% of pregnancies, putting mother and child at risk for increased morbidity and mortality. Cholestasis, portal hypertension, and liver failure represent three major clinical entities that should be recognized early because of the prognostic implications. Liver disease in pregnancy is generally separated into disorders that are unique to pregnancy and those that coincide with pregnancy. This chapter recommends a systematic approach that focuses on the major differential diagnostic characteristics of pregnancy-related liver diseases and a limited set of tests for pregnancy-unrelated liver diseases. Management of these conditions should be performed by a multidisciplinary team and ranges from simple medical therapies to immediate termination of the pregnancy.

scholarly journals TGF-β2 silencing to target biliary-derived liver diseases

Gut ◽  
2020 ◽  
Vol 69 (9) ◽  
pp. 1677-1690 ◽  
Author(s):  
Anne Dropmann ◽  
Steven Dooley ◽  
Bedair Dewidar ◽  
Seddik Hammad ◽  
Tatjana Dediulia ◽  
...  
Keyword(s):  
Liver Disease ◽  
Transforming Growth Factor Beta ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Inflammatory Cells ◽  
Mechanistic Explanation ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease

ObjectiveTGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.DesignAs we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on molecular, cellular and tissue levels.ResultsTgfB2-induced expression of fibrotic genes in cholangiocytes and hepatic stellate cellswas detected. TgfB2 expression in MDR2-KO mice was blunted using TgfB2-directed antisense oligonucleotides (AON). Upon AON treatment, reduced collagen deposition, hydroxyproline content and αSMA expression as well as induced PparG expression reflected a significant reduction of fibrogenesis without adverse effects on healthy livers. Expression analyses of fibrotic and inflammatory genes revealed AON-specific regulatory effects on Ccl3, Ccl4, Ccl5, Mki67 and Notch3 expression. Further, AON treatment of MDR2-KO mice increased tissue infiltration by F4/80-positive cells including eosinophils, whereas the number of CD45-positive inflammatory cells decreased. In line, TGFB2 and CD45 expression correlated positively in PSC/PBC patients and localised in similar areas of the diseased liver tissue.ConclusionsTaken together, our data suggest a new mechanistic explanation for amelioration of fibrogenesis by TGF-β2 silencing and provide a direct rationale for TGF-β2-directed drug development.

scholarly journals Novel Insights of Primary Sclerosing Cholangitis and Primary Biliary Cholangitis

2020 ◽  
Vol 25 (2) ◽  
pp. 107-117
Author(s):  
Dong-Won Ahn
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Acute Cholangitis ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are immune-mediated chronic liver diseases. PSC is a rare disorder characterized by multi-focal bile duct strictures and progressive liver diseases, in which liver transplantation is required ultimately in most patients. Imaging studies such as magnetic resonance cholangiopancreatography have important role in diagnosis in most cases of PSC. PSC is usually accompanied by inflammatory bowel disease and there is a high risk of cholangiocarcinoma and colorectal cancer in PSC. No medical therapies have been proven to delay progression of PSC. Endoscopic intervention for tissue diagnosis or biliary drainage is frequently required in cases of PSC with dominant stricture, acute cholangitis, or clinically suspected cholangiocarcinoma. PBC is a chronic inflammatory autoimmune cholestatic liver disease, which when untreated will culminate in endstage biliary cirrhosis requiring liver transplantation. Diagnosis is usually based on the presence of serum liver tests indicative of a cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse in PBC and risk stratification is important to ensure all patients receive a personalised approach to their care. Medical therapy using ursodeoxycholic acid (UDCA) or obeticholic acid (OCA) has an important role to reduce the progression to end-stage liver disease in PBC.

scholarly journals Medical Management of Chronic Cholestatic Liver Diseases

2000 ◽  
Vol 14 (suppl d) ◽  
pp. 93D-98D ◽  
Author(s):  
Andrea A Gossard ◽  
Keith D Lindor
Keyword(s):  
Liver Disease ◽  
Primary Biliary Cirrhosis ◽  
Primary Sclerosing Cholangitis ◽  
Liver Diseases ◽  
Biliary Obstruction ◽  
Sclerosing Cholangitis ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Management Options ◽  
Extrahepatic Biliary Obstruction

The purpose of the present review is to discuss the diagnosis and management of cholestatic liver diseases. Differential diagnoses to consider are described, including causes of extrahepatic biliary obstruction such as gallstones, strictures, extrabiliary malignancies and pancreatitis. In addition, diseases that cause intrahepatic cholestasis such as primary biliary cirrhosis, primary sclerosing cholangitis, hepatocellular diseases and a variety of miscellaneous causes including drugs that may cause cholestasis are discussed. Primary biliary cirrhosis and primary sclerosing cholangitis are reviewed in detail, and management options are identified. The prognosis of patients with these diseases is discussed, and the Mayo Mathematical Models in Cholestatic Liver Disease for both primary biliary cirrhosis and primary sclerosing cholangitis are provided. Finally, management options for the complications of cholestasis are provided.

scholarly journals Biliary System Architecture: Experimental Models and Visualization Techniques

2017 ◽  
pp. 383-390 ◽  
Author(s):  
L. SARNOVA ◽  
M. GREGOR
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Treatment Strategies ◽  
Biliary Tree ◽  
Experimental Models ◽  
Cholestatic Liver Disease ◽  
Toxic Substances ◽  
Bile Formation ◽  
Worldwide Population ◽  
Visualization Techniques

The complex architecture of the liver biliary network represents a structural prerequisite for the formation and secretion of bile as well as excretion of toxic substances through bile ducts. Disorders of the biliary tract affect a significant portion of the worldwide population, often leading to cholestatic liver diseases. Cholestatic liver disease is a condition that results from an impairment of bile formation or bile flow to the gallbladder and duodenum. Cholestasis leads to dramatic changes in biliary tree architecture, worsening liver disease and systemic illness. Recent studies show that the prevalence of cholestatic liver diseases is increasing. The availability of well characterized animal models, as well as development of visualization approaches constitutes a critical asset to develop novel pathogenetic concepts and new treatment strategies.

scholarly journals Multiparametric ultrasound in liver diseases: an overview for the practising clinician

2019 ◽  
Vol 95 (1126) ◽  
pp. 425-432 ◽  
Author(s):  
Ivica Grgurevic ◽  
Ida Tjesic Drinkovic ◽  
Massimo Pinzani
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Diagnostic Algorithm ◽  
Current Data ◽  
Chronic Liver ◽  
Focal Liver Lesions ◽  
Oesophageal Varices ◽  
Non Invasive ◽  
Practical Algorithms ◽  
Multiparametric Ultrasound

Ultrasound (US) is usually the first and most commonly used tool in the diagnostic algorithm for liver disease. It is widely available, non-invasive and offers a real-time assessment of the liver in several anatomic planes, using different US modalities such as greyscale imaging, Doppler, elastography and contrast-enhanced US. This multiparametric ultrasound (MPUS) provides more information of the examined structures and allows for a faster and more accurate diagnosis, usually at the point of care, thus reducing the requirement for some invasive and more expensive methods. Current data on the MPUS in hepatology are summarised in this review, mostly focused on its use for non-invasive staging of liver fibrosis, detection and classification of portal hypertension and oesophageal varices, prognosis in chronic liver diseases and characterisation of focal liver lesions (FLLs). Based on the available data, we propose practical algorithms for clinical use of MPUS in chronic liver disease and FLL.

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