scholarly journals Asthenia and fatigue in hyperammonemia: etiopathogenesis and methods of correction

2022 ◽  
pp. 95-104
Author(s):  
E. Yu. Plotnikova ◽  
M. N. Sinkova ◽  
L. K. Isakov
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Signs And Symptoms ◽  
Chronic Liver ◽  
Blood Levels ◽  
Chronic Liver Diseases ◽  
Life Threatening ◽  
Underlying Causes ◽  
Principles Of Treatment ◽  
The Brain

Asthenia and fatigue are the most common syndromes in patients with liver disease, which significantly affects their quality of life. The prevalence of fatigue in chronic liver diseases is from 50% to 85%. While some progress has been made in understanding the processes that can cause fatigue in general, the underlying causes of fatigue associated with liver disease remain not well understood. In particular, many data suggest that fatigue associated with liver disease likely results from changes in neurotransmission in the brain against the background of hyperammonemia. Hyperammonemia is a metabolic state characterized by an increased level of  ammonia, a  nitrogen-containing compound. The  present review describes hyperammonemia, which is likely important in the pathogenesis of fatigue associated with liver disease. Ammonia is a potent neurotoxin, its elevated blood levels can cause neurological signs and symptoms that can be acute or chronic, depending on the  underlying pathology. Hyperammonemia should be recognized early, and immediately treated to prevent the development of life-threatening complications, such as, swelling of the brain and coma. The article gives pathophysiological mechanisms of influence of hyperammonemia on state of psychovegetative status of patients with liver diseases, also lists basic principles of treatment. A significant part of the article is devoted to L-ornithine-L-aspartate, which is effective in asthenia and fatigue to reduce the level of hyperammonemia through a variety of well-studied mechanisms in chronic liver diseases.

Rationale for the use of statins in liver disease

2017 ◽  
Vol 312 (5) ◽  
pp. G407-G412 ◽  
Author(s):  
Robert Schierwagen ◽  
Frank Erhard Uschner ◽  
Fernando Magdaleno ◽  
Sabine Klein ◽  
Jonel Trebicka
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Treatment Options ◽  
Statin Treatment ◽  
Chronic Liver ◽  
Special Focus ◽  
Chronic Liver Diseases ◽  
End Stage Liver Disease ◽  
Life Threatening ◽  
End Stage

The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In addition to the primary effect, statins act beneficially through different pleiotropic mechanisms on inflammation, fibrosis, endothelial function, thrombosis, and coagulation to improve chronic liver diseases. However, concerns remain about the efficacy and safety of statin treatment because of their potential hepatotoxic risks, and as of now, these risks impede broader use of statins in the treatment of chronic liver diseases. The aim of this review is to comprehensively describe the mechanisms by which statins improve prospects for different chronic liver diseases with special focus on the pathophysiological rationale and the clinical experience of statin use in the treatment of liver diseases.

scholarly journals The Role of the Gut Microbiome in Liver Cirrhosis Treatment

2020 ◽  
Vol 22 (1) ◽  
pp. 199
Author(s):  
Na Young Lee ◽  
Ki Tae Suk
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

scholarly journals The Course Of Chronic Liver Disease In Patients With Covid-2019 (Literature Review And Own Data)

2021 ◽  
Vol 03 (09) ◽  
pp. 69-74
Author(s):  
Muxamedova Z.R. ◽  
Keyword(s):  
Liver Disease ◽  
Literature Review ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Biochemical Activity ◽  
Severe Liver ◽  
Risk Of Mortality ◽  
The World ◽  
Severe Liver Damage

The pandemic of the new coronavirus COVID-19 has switched medicine around the world on the primary fight against this infection. Patients with chronic liver diseases require increased attention of doctors during an epidemic, since against the background of an exacerbation of their disease, not only the risk of contracting the COVID 19 viral infection increases, but also its more severe course. Patients with confirmed COVID-19 with severe liver damage - high biochemical activity. According to some reports, patients with a severe course of COVID-19 have an increase in ALT levels, a decrease in the number of platelets, a decrease in the level of albumin, and a connection (although not all indicators) with a higher risk of mortality is possible.

scholarly journals Patients with chronic liver disease and COVID-19 (literature review and own data)

2021 ◽  
Vol 2 (2/S) ◽  
pp. 498-503
Author(s):  
D.H. Yuldasheva ◽  
Z.X. Muxamedova ◽  
N.S. Shadjanova
Keyword(s):  
Liver Disease ◽  
Literature Review ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Biochemical Activity ◽  
Severe Liver ◽  
Risk Of Mortality ◽  
The World ◽  
Severe Liver Damage

The pandemic of the new coronavirus COVID-19 has switched medicine around the world on the primary fight against this infection. Patients with chronic liver diseases require increased attention of doctors during an epidemic, since against the background of an exacerbation of their disease, not only the risk of contracting the COVID 19 viral infection increases, but also its more severe course. Patients with confirmed COVID-19 with severe liver damage - high biochemical activity. According to some reports, patients with a severe course of COVID-19 have an increase in ALT levels, a decrease in the number of platelets, a decrease in the level of albumin, and a connection (although not all indicators) with a higher risk of mortality is possible.

scholarly journals Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jayashree Bagchi Chakraborty ◽  
Fiona Oakley ◽  
Meagan J. Walsh
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Recent Literature ◽  
Primary Source ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Viral Hepatitis B ◽  
Fibrotic Scar ◽  
Fibrosis Regression ◽  
Nonalcoholic Liver Disease

Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD) nonalcoholic liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) viral hepatitis B and C (HBV, HCV). The critical step in the development of scar is activation of hepatic stellate cells (HSCs), which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression.

scholarly journals Prevalence and Clinical Significance of Immunoglobulin A Antibodies against Tissue Transglutaminase in Patients with Diverse Chronic Liver Diseases

2005 ◽  
Vol 12 (8) ◽  
pp. 941-948 ◽  
Author(s):  
Anastasios E. Germenis ◽  
Efthalia E. Yiannaki ◽  
Kalliopi Zachou ◽  
Violeta Roka ◽  
Sotirios Barbanis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Clinical Significance ◽  
Liver Diseases ◽  
Tissue Transglutaminase ◽  
Immunoglobulin A ◽  
Chronic Liver ◽  
Intestinal Biopsy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Liver Diseases ◽  
Hla Dq

ABSTRACT The prevalence of celiac disease (CD) and the prevalence and clinical significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large series of patients with chronic liver diseases were assessed. We studied 738 patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases, 113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were measured by enzyme-linked immunosorbent assay and a microsphere-based flow cytometric assay. Positive sera were investigated for IgA antiendomysial antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small-intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested tTGAb+ EmA+ and underwent a biopsy (CD confirmation in all). Four of 738 liver disease patients tested tTGAbs+ EmA+ (0.54%; not statistically significant). Two were HCV infected (1.24%; not statistically significant), and two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs+ EmA− (5.8%; P < 0.001 compared to HC). Inhibition experiments verified the existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients underwent a biopsy (all negative for CD). Binary logistic regression analysis revealed age (P = 0.008), cirrhosis (P = 0.004), alkaline phosphatase (P = 0.026), and antinuclear antibodies (P = 0.012) as independent risk factors for tTGAb reactivity among the patients. It was concluded that CD prevalence is the same in HC and patients with chronic liver diseases. The prevalence of tTGAbs is higher in hepatic patients compared to HC, but their specificity for CD diagnosis in this group of patients is low. tTGAbs in patients appear to be associated with the presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin of the liver disease.

scholarly journals Predictors of Quality of Life after Liver Transplant

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Joey Wu ◽  
Archita Desai, MD
Keyword(s):  
Quality Of Life ◽  
Liver Disease ◽  
General Population ◽  
Liver Transplant ◽  
Liver Diseases ◽  
Chronic Liver ◽  
University Hospital ◽  
Chronic Liver Diseases ◽  
The Impact

Background and Hypothesis: The impact of chronic liver diseases on patients and their family member is often understated and understudied. Chronic liver diseases can sometimes progress to a need for Liver transplant (LT). While recent studies have described quality of life (QOL) at different stages of liver disease, the impact of the patient’s QOL in LT survivors has not been examined. The importance of studying QOL in patients is due to its effect on the survivorship of LT recipients. We hypothesize that QOL in LT patients is lower than the general population. Our aim was to describe predictors of QOL in a well-described cohort of LT patients. Methods: Patients were enrolled at the Digestive and Liver Disease Liver clinic at Indiana University Hospital. All patients over the age of 18 were approached, if patients consented to the study, they were then enrolled during their liver follow up visit. The PROMIS survey was administered on an iPad and completed during the clinic visit. Survey were then scored and analyzed. Results: The T-scores for post liver transplant patients are lower in physical function, anxiety and depression, but higher in general life satisfaction compared to the general population. LT recipients have similar T-scores in Fatigue, Sleep disturbance, ability to participate in social activities, and pain interference compared to the general population. Conclusion and Potential Impact: Previous diagnosis of PBC, HCC, diagnosis of depression, household income, insurance status, Charlson Comorbid Index and number of non-transplant related medications have the highest association with quality of life. Further enrollment is needed to increase the power of the study. However, this can inform physicians the importance to taking these factors in to consideration in order to improve the QOL in LT recipients.

scholarly journals Elevation of Plasminogen Activator Inhibitor-1 promotes differentiation of Cancer Stem-like Cell state by Hepatitis C Virus infection

2021 ◽  
Author(s):  
Da-eun Nam ◽  
Angelina Angelucci ◽  
Dahsom Choi ◽  
Arnold Leigh ◽  
Hae Chang Seong ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Plasminogen Activator Inhibitor ◽  
Chronic Liver ◽  
Hcv Infection ◽  
Chronic Liver Diseases ◽  
Plasminogen Activator Inhibitor 1 ◽  
Akt Activation ◽  
Activator Inhibitor ◽  
Pai 1

Plasminogen activator inhibitor-1 (PAI-1) is a critical factor that regulates protein synthesis and degradation. The increased PAI-1 levels are detectable in the serum of patients with chronic hepatitis C virus (HCV) liver disease. The differentiation state and motility of HCV-induced cancer stem-like cells (CSC) play a major role in severe liver disease progression. However, the role of PAI-1 in the pathological process of chronic liver diseases remains unknown. In this study, we determined how PAI-1 affects the differentiation of CSC state in hepatocytes upon HCV infection. We found that HCV infection induced the expression of PAI-1 while decreasing miR-30c expression in Huh7.5.1 cells. Similar results were obtained from isolated hepatocytes from humanized liver mice after HCV infection. Moreover, decreased miR-30c expression in HCV-infected hepatocytes was associated with the increased levels of PAI-1 mRNA and protein. Notably, the increased PAI-1 levels resulted in the activation of Protein Kinase B/AKT, a major mediator of cell proliferation, in HCV-infected hepatocytes along with the increased expression of CSC markers such as Human Differentiated Protein (CD) 133, Epithelial cell adhesion molecule (EpCAM), Octamer 4 (Oct4), Nanog, Cyclin D1, and MYC. Moreover, blockade of PAI-1 activity by miR-30c mimic and anti-PAI-1 mAb abrogated the AKT activation with decreased expression of CSC markers. Our findings suggest that HCV infection induces the CSC state via PAI-1-mediated AKT activation in hepatocytes. It implicates that the manipulation of PAI-1 activity could provide potential therapeutics to prevent the development of HCV-associated chronic liver diseases. IMPORTANCE The progression of chronic liver disease by HCV infection is considered a major risk factor for hepatocellular carcinoma (HCC), one of the major causes of death from cancer. Recent studies have demonstrated that increased CSC properties in HCV-infected hepatocytes are associated with the progression of HCC. Since proteins and miRNAs production by HCV-infected hepatocytes can play various roles in physiological processes, investigating these factors can potentially lead to new therapeutic targets. However, the mechanism of HCV associated progression of hepatocytes to CSC remains unclear. Here we identify the roles of PAI-1 and miR-30c in the progression of CSC during HCV infection in hepatocytes. Our data shows that increased secretion of PAI-1 following HCV infection promotes this CSC state and activation of AKT. We report that the inhibition of PAI-1 by miR-30c mimic reduces HCV associated CSC properties in hepatocytes. Taken together, targeting this interaction of secreted PAI-1 and miR-30c in HCV-infected hepatocytes may provide a potential therapeutic intervention against the progression to chronic liver diseases and HCC.

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