Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
Expert Rev Clin Pharmacol ; 14(4): 457-464, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1467264

ABSTRACT

INTRODUCTION: Galectin-3 (Gal-3) is a ß-galactoside binding protein associated with many disease pathologies, including chronic inflammation and fibrogenesis. It has been implicated in the disease severity of NASH, although its precise role is unknown. Inhibition of Gal-3 has shown to improve and prevent fibrosis progression and has now reached phase III clinical trial in NASH patients. AREAS COVERED: This discusses the role of Gal-3 in NASH. It brings together the current findings of Gal-3 in NASH and hepatic fibrosis by analyzing recent data from animal model studies and clinical trials. EXPERT OPINION: Gal-3 inhibitors, in particular, Belapectin (GR-MD-02), have shown promising results for NASH with advanced fibrosis. In a phase 2 trial, Belapectin did not meet the primary endpoint. However, a sub-analysis of Belapectin among a separate group of patients without esophageal varices showed 2 mg/kg of GR-MD-02 reduced HVPG and the development of new varices. A subsequent study is under way, aiming to replicate the positive findings in phase 2 and demonstrate greater efficacy. If Belapectin is shown to be effective, it will be coupled with other drugs that target steatohepatitis to maximize efficacy and disease reversal.


Subject(s)
Blood Proteins/antagonists & inhibitors , Galectins/antagonists & inhibitors , Liver Cirrhosis/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Animals , Disease Models, Animal , Disease Progression , Humans , Liver Cirrhosis/metabolism , Liver Cirrhosis/physiopathology , Non-alcoholic Fatty Liver Disease/physiopathology , Pectins/administration & dosage , Pectins/pharmacology , Severity of Illness Index
2.
Dig Liver Dis ; 53(5): 525-533, 2021 05.
Article in English | MEDLINE | ID: covidwho-1062311

ABSTRACT

BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.


Subject(s)
COVID-19 , Fatty Liver , Liver Cirrhosis , Liver , Respiration, Artificial/statistics & numerical data , Aspartate Aminotransferases/blood , Biomarkers/blood , Blood Platelets/pathology , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Fatty Liver/diagnosis , Fatty Liver/epidemiology , Fatty Liver/metabolism , Female , Humans , Liver/diagnostic imaging , Liver/metabolism , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/metabolism , Liver Function Tests/methods , Male , Mexico/epidemiology , Middle Aged , Prognosis , Research Design , Retrospective Studies , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed/methods
3.
Eur Rev Med Pharmacol Sci ; 24(23): 12609-12622, 2020 12.
Article in English | MEDLINE | ID: covidwho-995022

ABSTRACT

OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.


Subject(s)
Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Cardiomyopathies/metabolism , Cytokine Release Syndrome/metabolism , Endothelium, Vascular/physiopathology , Liver Cirrhosis/metabolism , Systemic Inflammatory Response Syndrome/metabolism , Thrombosis/metabolism , Angiotensin I/metabolism , Atrial Fibrillation/metabolism , Atrial Fibrillation/physiopathology , Blood Coagulation , COVID-19/pathology , COVID-19/physiopathology , Capillary Permeability , Cardiomyopathies/pathology , Cardiomyopathies/physiopathology , Cytokine Release Syndrome/physiopathology , Cytokines/metabolism , Fibroblasts/metabolism , Fibroblasts/pathology , Fibrosis , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/physiopathology , Myocarditis/metabolism , Myocarditis/pathology , Myocarditis/physiopathology , Receptors, Coronavirus/metabolism , Renin-Angiotensin System , SARS-CoV-2/metabolism , Systemic Inflammatory Response Syndrome/physiopathology , Thrombosis/physiopathology , Virus Internalization
5.
Int J Mol Sci ; 21(15)2020 Jul 24.
Article in English | MEDLINE | ID: covidwho-699380

ABSTRACT

Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.


Subject(s)
Bacterial Infections , Dysbiosis , Gastrointestinal Microbiome , Liver Cirrhosis , Sarcopenia , Bacterial Infections/etiology , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Infections/pathology , Dysbiosis/etiology , Dysbiosis/metabolism , Dysbiosis/microbiology , Dysbiosis/pathology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/metabolism , Liver Cirrhosis/microbiology , Liver Cirrhosis/pathology , Sarcopenia/etiology , Sarcopenia/metabolism , Sarcopenia/microbiology , Sarcopenia/pathology
SELECTION OF CITATIONS
SEARCH DETAIL