scholarly journals Fibrinolysis in Patients with Liver Disease

2021 ◽  
Author(s):  
Fien A. von Meijenfeldt ◽  
Ton Lisman
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Bleeding Risk ◽  
Therapeutic Strategies ◽  
Decompensated Cirrhosis ◽  
Bleeding Tendency ◽  
Antifibrinolytic Therapy ◽  
Hemostatic System ◽  
The Relationship

AbstractPatients with liver disease acquire complex changes in their hemostatic system. Historically, these patients were considered to have a bleeding tendency related, in part, to a hyperfibrinolytic state. However, studies using more modern fibrinolysis tests have questioned the presence of a hyperfibrinolytic state in patients with liver disease and its association with bleeding risk. It may be that the sickest patients with liver disease do have fibrinolytic abnormalities. However, the debate on the fibrinolytic state of patients with (decompensated) cirrhosis or critically ill liver disease is complicated by the fact that hypo- and hyperfibrinolysis have been poorly defined. This could, in part, be explained by the lack of reliable tests that assess a patient's fibrinolytic status. Moreover, large clinical studies on the relationship between bleeding and fibrinolysis in patients with liver disease are scarce. Here, we provide an overview of the current knowledge on fibrinolysis in various types of liver diseases and possible implications as a target for therapeutic strategies in liver disease. As antifibrinolytic therapy has been shown to be safe and effective during liver transplantation, it could potentially be of use in patients with (either laboratory-established or suspected) hyperfibrinolysis-related bleeding.

scholarly journals Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qingfei Chu ◽  
Xinyu Gu ◽  
Qiuxian Zheng ◽  
Jing Wang ◽  
Haihong Zhu
Keyword(s):  
Cell Death ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Cellular Energetics ◽  
Liver Cell Death

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

scholarly journals Targeting Gut–Liver Axis for Treatment of Liver Fibrosis and Portal Hypertension

Livers ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 147-179
Author(s):  
Eric Kalo ◽  
Scott Read ◽  
Golo Ahlenstiel
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Biomarker Discovery ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Decompensated Cirrhosis ◽  
Microbial Composition ◽  
Medicine Development ◽  
And Personalized Medicine

Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis.

scholarly journals Data on Adiponectin from 2010 to 2020: Therapeutic Target and Prognostic Factor for Liver Diseases?

2020 ◽  
Vol 21 (15) ◽  
pp. 5242 ◽  
Author(s):  
Misaq Heydari ◽  
María Eugenia Cornide-Petronio ◽  
Mónica B. Jiménez-Castro ◽  
Carmen Peralta
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Therapeutic Target ◽  
Liver Diseases ◽  
Therapeutic Strategies ◽  
Potential Therapeutic Target ◽  
Surgical Interventions ◽  
Scientific Controversies

The review describes the role of adiponectin in liver diseases in the presence and absence of surgery reported in the literature in the last ten years. The most updated therapeutic strategies based on the regulation of adiponectin including pharmacological and surgical interventions and adiponectin knockout rodents, as well as some of the scientific controversies in this field, are described. Whether adiponectin could be a potential therapeutic target for the treatment of liver diseases and patients submitted to hepatic resection or liver transplantation are discussed. Furthermore, preclinical and clinical data on the mechanism of action of adiponectin in different liver diseases (nonalcoholic fatty disease, alcoholic liver disease, nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) in the absence or presence of surgery are evaluated in order to establish potential targets that might be useful for the treatment of liver disease as well as in the practice of liver surgery associated with the hepatic resections of tumors and liver transplantation.

scholarly journals Metabolic Fatty Liver Disease in Children: A Growing Public Health Problem

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1915
Author(s):  
Sébastien Le Garf ◽  
Véronique Nègre ◽  
Rodolphe Anty ◽  
Philippe Gual
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Chronic Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Overweight And Obesity ◽  
Chronic Liver ◽  
Nonalcoholic Fatty Liver

Metabolic-associated fatty liver disease (MAFLD), previously called nonalcoholic fatty liver diseases (NAFLD), is one of the most important causes of chronic liver disease worldwide and will likely become the leading cause of end-stage liver disease in the decades ahead. MAFLD covers a continuum of liver diseases from fatty liver to nonalcoholic steatohepatitis (NASH), liver fibrosis/cirrhosis and hepatocellular cancer. Importantly, the growing incidence of overweight and obesity in childhood, 4% in 1975 to 18% in 2016, with persisting obesity complications into adulthood, is likely to be harmful by increasing the incidence of severe MAFLD at an earlier age. Currently, MAFLD is the leading form of chronic liver disease in children and adolescents, with a global prevalence of 3 to 10%, pointing out that early diagnosis is therefore crucial. In this review, we highlight the current knowledge concerning the epidemiology, risk factors and potential pathogenic mechanisms, as well as diagnostic and therapeutic approaches, of pediatric MAFLD.

scholarly journals Interplay between Heart Disease and Metabolic Steatosis: A Contemporary Perspective

2021 ◽  
Vol 10 (8) ◽  
pp. 1569
Author(s):  
Mohammad Said Ramadan ◽  
Vincenzo Russo ◽  
Gerardo Nigro ◽  
Emanuele Durante-Mangoni ◽  
Rosa Zampino
Keyword(s):  
Liver Disease ◽  
Clinical Decision Making ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Clinical Decision ◽  
Alcoholic Fatty Liver ◽  
Systemic Manifestations ◽  
Independent Association ◽  
The Impact ◽  
The Relationship

The liver-heart axis is a growing field of interest owing to rising evidence of complex bidirectional interplay between the two organs. Recent data suggest non-alcoholic fatty liver disease (NAFLD) has a significant, independent association with a wide spectrum of structural and functional cardiac diseases, and seems to worsen cardiovascular disease (CVD) prognosis. Conversely, the effect of cardiac disease on NAFLD is not well studied and data are mostly limited to cardiogenic liver disease. We believe it is important to further investigate the heart-liver relationship because of the tremendous global health and economic burden the two diseases pose, and the impact of such investigations on clinical decision making and management guidelines for both diseases. In this review, we summarize the current knowledge on NAFLD diagnosis, its systemic manifestations, and associations with CVD. More specifically, we review the pathophysiological mechanisms that govern the interplay between NAFLD and CVD and evaluate the relationship between different CVD treatments and NAFLD progression.

scholarly journals Impact of Sarcopenia and Myosteatosis in Non-Cirrhotic Stages of Liver Diseases: Similarities and Differences across Aetiologies and Possible Therapeutic Strategies

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 182
Author(s):  
Annalisa Cespiati ◽  
Marica Meroni ◽  
Rosa Lombardi ◽  
Giovanna Oberti ◽  
Paola Dongiovanni ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Early Stage ◽  
Alcoholic Fatty Liver ◽  
Early Stages ◽  
Advanced Stages ◽  
Related Liver Disease ◽  
And Function ◽  
The Relationship

Sarcopenia is defined as a loss of muscle strength, mass and function and it is a predictor of mortality. Sarcopenia is not only a geriatric disease, but it is related to several chronic conditions, including liver diseases in both its early and advanced stages. Despite the increasing number of studies exploring the role of sarcopenia in the early stages of chronic liver disease (CLD), its prevalence and the relationship between these two clinical entities are still controversial. Myosteatosis is characterized by fat accumulation in the muscles and it is related to advanced liver disease, although its role in the early stages is still under researched. Therefore, in this narrative review, we firstly aimed to evaluate the prevalence and the pathogenetic mechanisms underlying sarcopenia and myosteatosis in the early stage of CLD across different aetiologies (mainly non-alcoholic fatty liver disease, alcohol-related liver disease and viral hepatitis). Secondly, due to the increasing prevalence of sarcopenia worldwide, we aimed to revise the current and the future therapeutic approaches for the management of sarcopenia in CLD.

Heterogeneity in Bleeding Tendency and Arthropathy Development in Individuals with Hemophilia

2021 ◽  
Vol 47 (02) ◽  
pp. 183-191
Author(s):  
Aisling M. Rehill ◽  
Seán McCluskey ◽  
James S. O'Donnell ◽  
Michael Dockal ◽  
Roger J.S. Preston ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Current Knowledge ◽  
Platelet Reactivity ◽  
Anticoagulant Activity ◽  
Bleeding Risk ◽  
Joint Disease ◽  
Patient Specific ◽  
Bleeding Tendency ◽  
Bleeding Events ◽  
Treatment Regimens

AbstractPeople with hemophilia (PWH) have an increased tendency to bleed, often into their joints, causing debilitating joint disease if left untreated. To reduce the incidence of bleeding events, PWH receive prophylactic replacement therapy with recombinant factor VIII (FVIII) or FIX. Bleeding events in PWH are typically proportional to their plasma FVIII or IX levels; however, in many PWH, bleeding tendency and the likelihood of developing arthropathy often varies independently of endogenous factor levels. Consequently, many PWH suffer repeated bleeding events before correct dosing of replacement factor can be established. Diagnostic approaches to define an individual's bleeding tendency remain limited. Multiple modulators of bleeding phenotype in PWH have been proposed, including the type of disease-causing variant, age of onset of bleeding episodes, plasma modifiers of blood coagulation or clot fibrinolysis pathway activity, interindividual differences in platelet reactivity, and endothelial anticoagulant activity. In this review, we summarize current knowledge of established factors modulating bleeding tendency and discuss emerging concepts of additional biological elements that may contribute to variable bleeding tendency in PWH. Finally, we consider how variance in responses to new gene therapies may also necessitate consideration of patient-specific tailoring of treatment. Cumulatively, these studies highlight the need to reconsider the current “one size fits all” approach to treatment regimens for PWH and consider therapies guided by the bleeding phenotype of each individual PWH at the onset of therapy. Further characterization of the biological bases of bleeding heterogeneity in PWH, combined with the development of novel diagnostic assays to identify those factors that modulate bleeding risk in PWH, will be required to meet these aspirations.

scholarly journals The Purinergic P2X7 Receptor-NLRP3 Inflammasome Pathway: A New Target in Alcoholic Liver Disease?

2021 ◽  
Vol 22 (4) ◽  
pp. 2139
Author(s):  
Brendan Le Daré ◽  
Pierre-Jean Ferron ◽  
Thomas Gicquel
Keyword(s):  
Liver Disease ◽  
Alcohol Consumption ◽  
Alcoholic Liver Disease ◽  
Kupffer Cells ◽  
Nlrp3 Inflammasome ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Purinergic Signaling ◽  
World Health ◽  
Alcoholic Liver Diseases

The World Health Organization has estimated that approximately 3 million deaths are attributable to alcohol consumption each year. Alcohol consumption is notably associated with the development and/or progression of many non-communicable inflammatory diseases—particularly in the liver. Although these alcoholic liver diseases were initially thought to be caused by the toxicity of ethanol on hepatocytes, the latest research indicates Kupffer cells (the liver macrophages) are at the heart of this “inflammatory shift”. Purinergic signaling (notably through P2X7 receptors and the NLRP3 inflammasome) by Kupffer cells appears to be a decisive factor in the pathophysiology of alcoholic liver disease. Hence, the modulation of purinergic signaling might represent a new means of treating alcoholic liver disease. Here, we review current knowledge on the pathophysiology of alcoholic liver diseases and therapeutic perspectives for targeting these inflammatory pathways.

scholarly journals Lipometabolism and Glycometabolism in Liver Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Hao-ran Ding ◽  
Jing-lin Wang ◽  
Hao-zhen Ren ◽  
Xiao-lei Shi
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Metabolic Disorders ◽  
Liver Metabolism ◽  
Metabolic Changes ◽  
The Body ◽  
Pathological State ◽  
Metabolic Imbalance ◽  
Life Threatening ◽  
The Relationship

The liver is the main metabolic organ in the body especially in lipometabolism and glycometabolism. Carbohydrates and fats disorders can result in insulin resistance in the liver. Metabolic imbalance can even lead to life-threatening conditions. Therefore, it is essential to maintain the normal metabolic function of the liver. When the liver is in a pathological state, liver metabolism homeostasis is damaged, and metabolic disorders will further aggravate liver disease. Consequently, it is essential to determine the relationship between liver diseases and metabolic disorders. Here we review a lot of evidence that liver diseases are closely related to lipometabolism and glycometabolism. Although the disorder of the liver metabolism is caused by different liver diseases, the break of metabolic balance is determined by changes in the state of the liver. We discuss the relationship between liver disease and metabolic changes, outline the process of how metabolic changes are regulated by liver diseases, and describe the role which metabolic changes play in the process and prognosis of liver disease.

scholarly journals Review on Biological Characteristics of Kv1.3 and Its Role in Liver Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Junda Liu ◽  
Xiong-Wen Lv ◽  
Lei Zhang ◽  
Hua Wang ◽  
Jun Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Common Mechanism ◽  
Liver Macrophages ◽  
Prevention And Treatment ◽  
New Ideas ◽  
The Relationship

The liver accounts for the largest proportion of macrophages in all solid organs of the human body. Liver macrophages are mainly composed of cytolytic cells inherent in the liver and mononuclear macrophages recruited from the blood. Monocytes recruitment occurs mainly in the context of liver injury and inflammation and can be recruited into the liver and achieve a KC-like phenotype. During the immune response of the liver, macrophages/KC cells release inflammatory cytokines and infiltrate into the liver, which are considered to be the common mechanism of various liver diseases in the early stage. Meanwhile, macrophages/KC cells form an interaction network with other liver cells, which can affect the occurrence and progression of liver diseases. From the perspective of liver disease treatment, knowing the full spectrum of macrophage activation, the underlying molecular mechanisms, and their implication in either promoting liver disease progression or repairing injured liver tissue is highly relevant from a therapeutic point of view. Kv1.3 is a subtype of the voltage-dependent potassium channel, whose function is closely related to the regulation of immune cell function. At present, there are few studies on the relationship between Kv1.3 and liver diseases, and the application of its blockers as a potential treatment for liver diseases has not been reported. This manuscript reviewed the physiological characteristics of Kv1.3, the relationship between Kv1.3 and cell proliferation and apoptosis, and the role of Kv1.3 in a variety of liver diseases, so as to provide new ideas and strategies for the prevention and treatment of liver diseases. In short, by understanding the role of Kv1.3 in regulating the functions of immune cells such as macrophages, selective blockers of Kv1.3 or compounds with similar functions can be applied to alleviate the progression of liver diseases and provide new ideas for the prevention and treatment of liver diseases.

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