scholarly journals The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2959
Author(s):  
Kevin De Muynck ◽  
Bart Vanderborght ◽  
Hans Van Vlierberghe ◽  
Lindsey Devisscher

Chronic liver disease (CLD) is a growing health concern which accounts for two million deaths per year. Obesity, alcohol overconsumption, and progressive cholestasis are commonly characterized by persistent low-grade inflammation and advancing fibrosis, which form the basis for development of end-stage liver disease complications, including hepatocellular carcinoma. CLD pathophysiology extends to the intestinal tract and is characterized by intestinal dysbiosis, bile acid dysregulation, and gut barrier disruption. In addition, macrophages are key players in CLD progression and intestinal barrier breakdown. Emerging studies are unveiling macrophage heterogeneity and driving factors of their plasticity in health and disease. To date, in-depth investigation of how gut–liver axis disruption impacts the hepatic and intestinal macrophage pool in CLD pathogenesis is scarce. In this review, we give an overview of the role of intestinal and hepatic macrophages in homeostasis and gut–liver axis disruption in progressive stages of CLD.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Margret Paar ◽  
Vera H. Fengler ◽  
Daniel J. Rosenberg ◽  
Angelika Krebs ◽  
Rudolf E. Stauber ◽  
...  

AbstractHuman serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients’ HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin’s inherent flexibility.


2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Dr. Moni Chaudhary

Hepatitis C virus (HCV) infection is the leading cause of chronic liver disease which affects over 150 million individuals worldwide. Without treatment, one third of patients will develop cirrhosis and complications of end-stage liver disease. In India, the majority of chronic liver disease and related deaths are attributable to hepatitis C. People with HCV infection are likely to have poorer health related quality of life, physical, mental, psychosocial and neuropsychiatric problems. These problems are challenges for management of HCV infection. Mental health treatment is considered crucial in the overall management of HCV infection. A supportive environment and a nonjudgmental healthcare team are required for optimal medical and psychological management of patients with HCV. We present a comparison between mental health of patients with HCV infection in India and globally.


Gut ◽  
2020 ◽  
pp. gutjnl-2020-320786 ◽  
Author(s):  
Thomas Henry Tranah ◽  
Lindsey A Edwards ◽  
Bernd Schnabl ◽  
Debbie Lindsay Shawcross

Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mucosal immune homoeostasis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies targeted at restoring intestinal eubiosis, augmenting gut barrier function and ameliorating the mucosal and systemic immune deficits that characterise and define the course of decompensated cirrhosis.


2001 ◽  
Vol 85 (04) ◽  
pp. 667-670 ◽  
Author(s):  
Magdalene George ◽  
Jawed Fareed ◽  
David Van Thiel

SummaryThrombin Activatable Fibrinolysis Inhibitor (TAFI) is a 60 κD glycoprotein present in plasma that regulates fibrinolysis by limiting the amount of fibrin available for fibrinolysis by tissue plasminogen activator (t-PA). Chronic liver disease is well-known to be associated with a low-grade fibrinolytic syndrome that under the appropriate stimulus proceeds to an overt disseminated intravascular coagulopathy (DIC) with demonstrable bleeding. In the present study, TAFI activity was measured in the plasma of 74 patients with advanced liver disease, and the levels of TAFI were related to those of other important coagulation and fibrinolytic factors. TAFI levels were very low and essentially undetectable in the plasma of patients with advanced hepatocellular liver disease. No relationship with the degradation products of fibrin was evident.


2019 ◽  
Vol 18 (2) ◽  
pp. 53-59
Author(s):  
Rahul Pathak ◽  
Sabin Thapaliya

Introduction: Granulocyte colony stimulating factor improves short-term survival and clinical outcomes in alcoholic hepatitis, acute-on-chronic liver failure and decompensated chronic liver disease. Our study aimed to assess survival benefit and change in Child-Turcotte-Pugh and Model For End-Stage Liver Disease scores 30 days after Granulocyte colony stimulating factor therapy in chronic liver disease patients, irrespective of their mode of presentation. Methods: This was a prospective observational study conducted in a university teaching hospital, where 25 patients with chronic liver disease were given 300 micrograms of Granulocyte colony stimulating factor subcutaneously 12 hourly plus standard medical therapy. We assessed survival until day 30. Child-Turcotte- Pugh and Model For End-Stage Liver Disease scores at enrolment and 30 days after treatment were compared. Results: 21 of 25 patients treated with Granulocyte colony stimulating factor survived at day 30. Treatment with Granulocyte colony stimulating factor reduced Child-Turcotte-Pugh score from 10.33 ± 1.24 to 8.76 ± 1.79 (p< 0.001) at day 30 and Model For End-Stage Liver Disease score from 22.10 ± 4.67 to 16.38 ± 5.52 (p < 0.001) at day 30. Conclusions: Granulocyte colony stimulating factor improves clinical outcome, Child-Turcotte-Pugh and Model For End-Stage Liver Disease scores in patients admitted with chronic liver disease for any cause. Further studies are needed to explore whether lower doses (total six doses) of Granulocyte colony stimulating factor are as effective as higher doses (total 10 doses). 


2021 ◽  
Vol 8 (25) ◽  
pp. 2222-2228
Author(s):  
Jasmine Kaur ◽  
Navjot Kaur ◽  
Jasleen Kaur ◽  
Navjot Kaur Layal ◽  
Gurkiran Kaur

BACKGROUND Chronic liver diseases frequently are associated with haematological abnormalities. Anaemia occurs in about 75% of patients with chronic liver disease. The most common type of anaemia seen in liver cirrhosis is normocytic normochromic anaemia, due to the chronic inflammatory state, blood loss from oesophageal and rectal varices. The purpose of this study was to study the haematological manifestations in patients with chronic liver disease. METHODS A cross-sectional observational study was conducted at Sri Guru Ram Das Institute of Medical Sciences and Research (March 2019 - March 2020). Total of 90 patients with chronic liver disease were included in the study. The population was divided into 2 groups based on the model for end-stage liver disease (MELD) score and the various haematological abnormalities were assessed in these 2 groups. Similarly, haemoglobin (Hb) levels were assessed in 3 groups based on the ChildTurcotte-Pugh (CTP) classification. RESULTS There was a significant correlation between hemoglobina and CTP class (P < 0.001), with the lowest haemoglobin levels in CTP class C group. The correlation coefficient of MELD score and haemoglobin was -0.504 which was significant statistically. Thus, confirming the fact that haemoglobin levels decreases with the progress in the severity of liver cirrhosis. Of 39 patients with haemoglobin < 8 g/dl, 5 (12.8 %) had a MELD score of < 12, whereas 34 patients (87.2 %) had a MELD score of > 12 and was statistically significant (P < 0.0001). Leukocytosis was observed in 41 patients and leucopoenia in 14 patients. The mean prothrombin time was 20.4 seconds and 80 % of the patients had prothrombin time prolonged by more than 6 sec indicating liver damage alters coagulation profile. CONCLUSIONS We found an association between anaemia and indicators of advanced liver disease such as a higher MELD and CPS scores. This study inferred that levels of haemoglobin decrease as the severity of liver disease progresses. Thus, this measure can be used in the initial assessment of cirrhosis patients that needs urgent identification and correction to reduce morbidity and mortality. KEYWORDS Anaemia, Liver Cirrhosis, Model for End-Stage Liver Disease Score, Child-TurcottePugh Class


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