scholarly journals Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chandra Chiappin Cardoso ◽  
Camila Matiollo ◽  
Carolina Hilgert Jacobsen Pereira ◽  
Janaina Santana Fonseca ◽  
Helder Emmanuel Leite Alves ◽  
...  

AbstractLiver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.

2019 ◽  
Vol 28 (5) ◽  
pp. 432-441 ◽  
Author(s):  
Alexandru Radu Mihailovici ◽  
Ionuț Donoiu ◽  
Dan Ionuț Gheonea ◽  
Oana Mirea ◽  
Georgică Costinel Târtea ◽  
...  

Objective: Liver cirrhosis is associated with several cardiovascular abnormalities including a hyperdynamic splanchnic and systemic circulation related to arterial vasodilatation, finally leading to sodium retention, central hypovolemia, and increased intravascular volume. The objective of this study was to evaluate the relationship between NT-proBNP and echocardiographic parameters and liver disease stage in patients with cirrhosis. Method: This prospective study included 82 consecutive patients diagnosed with liver cirrhosis and 120 healthy, age- and sex-matched subjects. Standard transthoracic echocardiography was performed in all patients. Plasma NT-proBNP levels were determined. Liver disease severity in patients with cirrhosis was established by Child-Pugh class, MELD score and presence/absence of ascites. Results: Plasma levels of NT-proBNP were significantly higher in cirrhotic patients than the corresponding levels in the healthy subjects. NT-proBNP levels were also significantly elevated in Child-Pugh class C patients compared to those in class B and A. Left atrium (LA) size, diastolic function, left ventricular (LV) wall thickness, and LV ejection fraction were significantly altered in cirrhotic patients compared to controls. Advanced cirrhosis and high levels of NT-proBNP were significantly associated with increased LA volume and signs of cardiac diastolic dysfunction. We also observed significant differences between quartile groups of MELD score for the following: NT-proBNP, Troponin I, LA volume, left ventricle wall thickness, lateral wall and septum systolic tissue Doppler velocities and global longitudinal strain. Conclusion: NT-proBNP is increased in patients with cirrhosis and is correlated with the severity of liver disease as established by Child-Pugh class, MELD score, and the presence of ascites.


Author(s):  
Ahmed Abdelrahman Mohamed Baz ◽  
Rana Magdy Mohamed ◽  
Khaled Helmy El-kaffas

Abstract Background Liver cirrhosis is a multi-etiological entity that alters the hepatic functions and vascularity by varying grades. Hereby, a cross-sectional study enrolling 100 cirrhotic patients (51 males and 49 females), who were diagnosed clinically and assessed by model for end-stage liver disease (MELD) score, then correlated to the hepatic Doppler parameters and ultrasound (US) findings of hepatic decompensation like ascites and splenomegaly. Results By Doppler and US, splenomegaly was evident in 49% of patients, while ascites was present in 44% of them. Increased hepatic artery velocity (HAV) was found in70% of cases, while 59% showed reduced portal vein velocity (PVV). There was a statistically significant correlation between HAV and MELD score (ρ = 0.000), but no significant correlation with either hepatic artery resistivity index (HARI) (ρ = 0.675) or PVV (ρ =0.266). Moreover, HAV had been correlated to splenomegaly (ρ = 0.000), whereas HARI (ρ = 0.137) and PVV (ρ = 0.241) did not significantly correlate. Also, ascites had correlated significantly to MELD score and HAV (ρ = 0.000), but neither HARI (ρ = 0.607) nor PVV (ρ = 0.143) was significantly correlated. Our results showed that HAV > 145 cm/s could confidently predict a high MELD score with 62.50% and 97.62 % sensitivity and specificity. Conclusion Doppler parameters of hepatic vessels (specifically HAV) in addition to the US findings of hepatic decompensation proved to be a non-invasive and cost-effective imaging tool for severity assessment in cirrhotic patients (scored by MELD); they could be used as additional prognostic parameters for improving the available treatment options and outcomes.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Mohamed Abd Ellatif Afifi ◽  
Ahmed Mohamed Hussein ◽  
Mahmoud Rizk

Background. Patients with liver cirrhosis experience a large variety of metabolic disorders associated with more hepatic decompensation. Hepatic encephalopathy (HE) is a significant complication in liver cirrhosis patients, presenting a wide spectrum of neuropsychological symptoms. A deficiency of 25-hydroxy vitamin D (25-OHD) in the general population is associated with a loss of cognitive function, dementia, and Alzheimer’s disease. Aim of the Study. Our study aims to check the relationship between low serum 25-OHD and HE in patients with HCV-related liver cirrhosis and assess its link with patient mortality. Patients and Methods. This study was observationally carried out on 100 patients with HCV-related liver cirrhosis. The patients were divided into 2 groups: Group A—included 50 HCV-related cirrhotic patients with HE, and Group B—included 50 HCV-related cirrhotic patients without HE. Assessment of disease severity using the end-stage liver disease (MELD) model and Child Turcotte Pugh (CTP) scores were done, and 25-OHD levels were measured. Comparison of vitamin D levels in different etiologies and different CTP categories was made using one-way ANOVA. Pearson’s correlation between the level of vitamin D and other biomarkers was applied. Results. There was a statistically significant Vitamin D level difference between the two groups. A lower level of vitamin D was observed in the HE group where the severe deficiency was 16%, while it was 6% in the other group and the moderate deficiency was 24% in HE group as compared to 10% in the other group. The insufficient vitamin D level represented 46% of the non-HE group while none of the HE group falls in this category. Vitamin D level was statistically higher in Grade 1 HE than in Grade 2 which is higher than in Grades 3 to 4. Vitamin D level was also significantly higher in those who improved from HE as compared to those who died. Conclusion. The lower levels of 25-OHD were associated with the higher incidence of HE in cirrhotic HCV patients. The worsening vitamin D deficiency was associated with increased severity of the liver disease, so vitamin D may be considered a prognostic factor for the severity of liver cirrhosis and high mortality rate in HE patients.


1977 ◽  
Author(s):  
S. Coccheri ◽  
G. Palareti ◽  
M. Poggi ◽  
G. Oca

Positivity of paracoagulation tests in a previously studied group of 80 patients with chronic active liver disease did not exceed 5-10% of the cases. In the present study, plasma samples from 20 cases of decompensated liver cirrhosis, assessed by liver biopsy, were investigated by means of agarose cromatography. Fibrinogen related materials were measured immunologically and by Staphylococcal Clumping Test.First appearance of fibrinogen-like materials occurred at earlier fractions in cirrhotic patients in comparison with normal controls. The relative amount of soluble fibrin monomer complexes (SFMC) as referred to total fibrinogen was significantly increased. No correlation was found between the amount of SFMC and the severity of fibrinogen polymerisation defect.Circulating SFMC are therefore present in severe liver cirrhosis. However, DIC may not be the only proposed explanation for this finding.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S344-S344
Author(s):  
Patricia Saunders-Hao ◽  
Sumeet Jain ◽  
Bruce Hirsch ◽  
Pranisha Gautam-Goyal

Abstract Background Remdesivir is a nucleotide analogue antiviral that was FDA approved for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Remdesivir has been associated with elevations in serum aminotransferase levels but most cases being mild to moderate and reversible upon discontinuation. Although national COVID-19 guidelines and the American Association for the Study of Liver Diseases (AASLD) currently recommend remdesivir for use in hospitalized patients requiring supplemental oxygen, data is limited using remdesivir in patients with chronic liver disease. Here, we describe our experience with remdesivir in patients with liver cirrhosis. Methods Patients with liver cirrhosis who received remdesivir were identified either prospectively or retrospectively by primary or secondary ICD-10 codes indicating liver disease. Data collected included patient demographics, underlying cause of cirrhosis, co-morbidities, Child-Pugh score, laboratory values (serum aminotransferase levels, serum creatinine) during and following remdesivir, adverse reactions attributed to remdesivir, and mortality (in-hospital, 30-day, and 90-day). Results A total of 4 patients with underlying liver cirrhosis completed a 5-day course of remdesivir treatment. On admission, Child-Pugh class was A for 1 patient, B for 2 patients, and C for 1 patient. Causes for cirrhosis were nonalcoholic steatohepatitis (NASH), hepatic amyloidosis, and chronic hepatitis B. There were no acute elevations in aminotransferase levels or adverse events attributed to remdesivir therapy. Mortality was high with 50% in-hospital mortality. Of the 2 other patients who survived to discharge, one was discharged to home hospice and the other was readmitted within 30 days and expired during that admission. Conclusion Since there is limited data available using remdesivir in patients with advanced liver disease, we did not identify any safety concerns related to remdesivir in our cirrhotic patients. Mortality was high illustrating the poor outcomes of patients with advanced liver disease and COVID-19. Patients with cirrhosis should be offered remdesivir if clinically appropriate. Disclosures All Authors: No reported disclosures


2021 ◽  
Author(s):  
Sara Konstantin Nissen ◽  
Kristine Farmen ◽  
Mikkel Carstensen ◽  
Claudia Schulte ◽  
David Goldeck ◽  
...  

AbstractBackgroundAlpha-synuclein aggregates and accumulation are associated with immune activation and neurodegeneration in Parkinson’s disease. The immune activation is not only dependent on the brain-resident microglial cells but also involves peripheral immune cells, such as mononuclear phagocytes including monocytes and dendritic cells, found in the blood as well as infiltrated into the brain. Understanding the involvement of the peripheral immune component in Parkinson’s disease is essential for the development of immunomodulatory treatment, which might modify disease progression. We aimed to study the profile of circulating mononuclear phagocytes in early- and late-stage Parkinson’s disease by analyzing surface-expressed molecules related to phagocytosis, alpha-synuclein sensing, and tissue-migration.MethodsMulti-color flow cytometry on peripheral mononuclear cells from cross-sectional samples of 80 gender-balance individuals with early- and late-stage sporadic Parkinson’s disease, and 29 controls, as well as longitudinal samples from seven patients and one control. Cells were delineated into natural killer cells, monocyte subtypes, and dendritic cells with cell frequencies and surface marker expressions compared between patients and controls, and correlated with standardized clinical motor and non-motor scores.ResultsOverall, we found elevated frequencies and surface levels of markers related to migration (CCR2, CD11b) and phagocytosis (CD163) particularly on the elevated classical and intermediate monocytes in patients with Parkinson’s disease for less than five years. This corresponded to a decrease of non-classical monocytes and dendritic cells. We observed an increased HLA-DR expression late in disease and sexual-dimorphism with TLR-4 expression decreased in women with PD but not in males. The disease-associated immune changes on TLR4, CCR2, and CD11b were correlated with non-motor symptoms such as olfaction or cognition. While many alterations were normalized at late disease stage, other changes remained, such as the increased HLA-DR and CD163 expressions.ConclusionsOur data highlight a role for peripheral CD163+ and migration-competent classical monocytes in Parkinson’s disease. The study further suggests that the peripheral immune system is dynamically altered in Parkinson’s disease stages and directly related to both non-motor symptoms and the sex-bias of the disease.


2021 ◽  
Author(s):  
Haruki Uojima ◽  
Xue Shao ◽  
Taeang Arai ◽  
Yuji ogawa ◽  
Toru Setsu ◽  
...  

Patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6-superfamily member 2 (TM6SF2) polymorphisms have major impact for fibrosis due to steatohepatitis. However, there are scant data about correlations between cirrhosis-related complications and the polymorphisms of these genes. Therefore, we aimed to determine the role of the PNPLA3 and TM6SF2 polymorphisms in fibrosis progression for patients with liver cirrhosis. A multicenter study was performed at six hospitals in Japan enrolling 400 patients with liver cirrhosis caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33). These cirrhotic patients included those with complications of variceal bleeding, hepatic ascites, and/or hepatic encephalopathy and those without. To assess the role of the PNPLA3 and TM6SF2 polymorphisms in patients with cirrhosis related complications, we calculated the odds ratio and relative risk for the rs738409 and rs58542926 polymorphisms. We also accessed whether or not the interaction between these two polymorphisms contributed to cirrhosis related complications. As a result, the odds ratio for complications in the NAFLD group significantly increased in the presence of the rs738409 GG genotype when the CC genotype was used as the reference. There were no significant risks between complications and the presence of the rs738409 G allele in the virus or alcohol groups. There were no significant risks of complications in the frequency of the rs58542926 T polymorphism regardless of the etiology of liver cirrhosis. The interaction between the trs738409 and rs58542926 polymorphisms had the highest odds ratio of 2.415 for complications in the rs738409 GG + rs58542926 (CT+TT) group when rs738409 (CC+CG) + TM6SF2 CC was used as the reference in the NAFLD group.


Author(s):  
Cláudia Debona Mocelin ◽  
Filipe Bissoli ◽  
Rafaella De Nadai ◽  
Ana Paula Hamer Sousa Clara ◽  
Felipe Bertollo Ferreira ◽  
...  

Introdução: A cirrose hepática é uma doença crônica que cursa com diversas repercussões sistêmicas, uma delas é a disfunção cardiovascular, caracterizada pela queda da resistência vascular periférica e pelo aumento compensatório do débito cardíaco. Tal disfunção manifesta-se principalmente em situações de estresse hemodinâmico, estando muitas vezes normal no repouso. Objetivo: Avaliar a aplicabilidade do Teste de Caminhada de 6 minutos (TC6min) como instrumento sugestivo de disfunção cardiovascular nos pacientes cirróticos, através da correlação entre o desempenho no teste e o status funcional do paciente. Material e Métodos: Trata-se de estudo observacional e transversal do tipo inquérito, realizado em vinte e nove pacientes cirróticos, submetidos ao TC6min. Foram avaliados a distância percorrida por eles e parâmetros clínicos antes e após o teste, sendo o resultado comparado de acordo com sua classificação funcional. Resultados: Dentre os pacientes classe A de Child-Pugh, 6 deles (26,09% do total dessa classe) não atingiram a distância mínima prevista para o TC6min. Ao se analisar a classe B de Child-Pugh, 5 deles (83,33% do total dessa classe) não atingiram a distância mínima. A média da distância percorrida para pacientes Child A foi de 631,5 m, enquanto o previsto foi de 587,2 m. Em relação aos pacientes Child B, a média da distância percorrida foi de 441,0 m, com distância prevista de 541,2m. Foi observada uma significativa correlação inversa entre a distância percorrida e o escore de Child-Pugh (p=0,001). Conclusão: A distância percorrida no teste de caminhada de 6 minutos apresentou correlação inversa com a classificação de Child-Pugh-Turcotte o que demonstra um prejuízo funcional paralelo à piora da doença hepática de base. Ao considerar que os pacientes do estudo não apresentavam comorbidades previamente diagnosticadas que pudessem justificar tal prejuízo, essa associação pode indicar disfunção cardiovascular. Esta, por sua vez, provavelmente está relacionada ao comprometimento sistêmico secundário à cirrose hepática.Descritores: Doenças cardiovasculares, Cardiomiopatias, Cirrose hepática. Triagem, Teste de caminhadaAbstractIntroduction: Hepatic cirrhosis is a chronic disease that has several systemic repercussions. One of them is the cardiovascular dysfunction, characterized by the decrease of the peripheral vascular resistance and the compensatory increase of the cardiac output. Such dysfunction manifests itself mainly in situations of hemodynamic stress, and is often normal at rest. Objective: To evaluate the applicability of the 6-minute walk test (6MinWT) as an instrument suggestive of cardiovascular dysfunction in cirrhotic patients, through correlation between the test performance and the functional status of the patient. Methods: This is an observational and cross-sectional study of the survey type, performed in twenty-nine cirrhotic patients submitted to 6MinWT. The distance walked by them and the clinical parameters before and after the test were evaluated, and  the results were compared according to their functional classification. Results: Among Child-Pugh A patients, 6 (26.09% of the total of this class) did not reach the minimum distance predicted for the 6MWT. Analyzing the Child-Pugh B, 5 of them (83.33% of the total of this class) did not reach the minimum distance. The mean distance performed by Child A patients was 631.5 m, while the predicted distance was 587.2 m. In relation to Child B patients, the average distance performed was 441.0 m, with an expected distance of 541.2 m. A significant inverse correlation was observed between the distance walked and the Child-Pugh score (p = 0.001). Conclusion: The distance walked in the 6-minute walk test showed an inverse correlation with the Child-Pugh-Turcotte classification, which demonstrates a functional impairment parallel to the worsening of the underlying liver disease. Considering that the studied patients did not present previously diagnosed comorbidities that could justify such impairment, this association may indicate cardiovascular dysfunction. This, in turn, is probably related to systemic involvement secondary to liver cirrhosis. Key words: Cardiovascular diseases, Cardiomyopathies, Liver cirrhosis, Triage, Walk test. 


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