B-cell compartment abnormalities are associated with ACLF and mortality in patients with liver cirrhosis

Cardoso, Chandra Chiappin; Matiollo, Camila; Pereira, Carolina Hilgert Jacobsen; Fonseca, Janaína Sant'Ana; Alves, Helder Emmanuel Leite; Silva, Otávio Marcos da; Menegassi, Vivian de Souza; Schiavon, Leonardo de Lucca; Santos-Silva, Maria Cláudia

doi:10.1016/j.clinre.2021.101698

Cited by 8 publications

(6 citation statements)

References 44 publications

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“…In this study, CIBERSORT and xCell were used to assess the richness of member cell types in a mixed cell population with gene expression data. It has been reported that B‐cell subsets are markedly altered in cirrhotic patients, and the compartment abnormalities are associated with mortality in patients with liver cirrhosis 31 . In the present study, both naive and memory B cells were found to be significantly different between the two subclasses using a different algorithm.…”

Section: Discussionmentioning

confidence: 42%

“…It has been reported that B-cell subsets are markedly altered in cirrhotic patients, and the compartment abnormalities are associated with mortality in patients with liver cirrhosis. 31 In the present study, both naive and memory B cells were found to be significantly different between the two subclasses using a different algorithm. T cells are the important effector cells in adaptive immunity that fight viral infections.…”

Section: Discussionmentioning

confidence: 45%

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Classification and survival prediction in early‐stage cirrhosis by gene expression profiling

Wang

Chen

et al. 2022

Journal of Viral Hepatitis

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Liver cirrhosis has been increasingly diagnosed at an early stage owing to the noninvasive diagnostic techniques. However, it is difficult to identify patients at high risk of disease progression. Screening cirrhotic patients with poor prognosis who are most in need of surveillance is still challenging. Gene expression data GSE15654 and GSE14520 were downloaded for performing unsupervised clustering analysis. The prognostic differences between the different clusters were explored by Cox regression. Integrative analysis of gene expression signature, immune cell enrichments and clinical characterization was performed for different clusters. Two distinctive subclasses were identified in HCV-related GSE15654, and Kaplan-Meier analysis indicated that subtype 2 had lower survival rates than subtype 1 (p = 0.0399). Further analysis revealed subtype 2 had a higher density of follicular T helper cells, resting natural killer cells and M0, M2 macrophages while subtype 1 with a higher fraction of naive B cells, memory B cells, resting memory CD 4 T cells, activated natural killer cells and monocytes. 226 differentially expressed genes were identified between the two subtypes, and Reactome analysis showed the mainly enriched pathways were biological oxidations and fatty acid metabolism. Five hub genes (AKT1, RPS16, CDC42, CCND1 and PCBP2) and three significant modules were extracted from the PPI network. The results were validated in HBV-related GSE14520 cohort. We identified two subtypes of patients with different prognosis for hepatitis C-related early-stage liver cirrhosis. Bioinformatics analysis of the gene expression and immune cell profile may provide fresh insight into understanding the prognosis difference. K E Y W O R D Simmune cells, liver cirrhosis, microarray analysis, prognosis, unsupervised clustering | INTRODUC TI ONCirrhosis results from many forms of chronic liver damage and hepatitis C virus (HCV) infection is one of the major aetiologies. 1 HCV-related cirrhosis is a common and growing public health problem globally. 2 The wide use of non-invasive diagnostic techniques promises to increase the number of newly identified patients with early-stage liver cirrhosis. 3 Clinical management of this growing patient population poses challenges for current medical resources. Despite a sustained virologic response being achieved after antiviral therapy, HCV eradication is not generally sufficient to eliminate the risk of the cirrhosis complications. 4 The mortality is mainly

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Section: Discussionmentioning

confidence: 42%

Section: Discussionmentioning

confidence: 45%

Classification and survival prediction in early‐stage cirrhosis by gene expression profiling

Wang

Chen

et al. 2022

Journal of Viral Hepatitis

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“…In line, the presence of sepsis was associated with an almost twofold increased risk of death in our multivariate regression analysis. On a molecular level, both monocyte and neutrophil dysfunctions [38,39], as well as B-cell compartment abnormalities [40], have been described as a pathophysiological link for this observation.…”

Section: Variablementioning

confidence: 99%

Clinical determinants of hospital mortality in liver failure: a comprehensive analysis of 62,717 patients

et al. 2023

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Background Liver failure (LF) is characterised by a loss of the synthetic and metabolic liver function and is associated with a high mortality. Large-scale data on recent developments and hospital mortality of LF in Germany are missing. A systematic analysis and careful interpretation of these datasets could help to optimise outcomes of LF. Methods We used standardised hospital discharge data of the Federal Statistical Office to evaluate current trends, hospital mortality and factors associated with an unfavourable course of LF in Germany between 2010 and 2019. Results A total of 62,717 hospitalised LF cases were identified. Annual LF frequency decreased from 6716 (2010) to 5855 (2019) cases and was higher among males (60.51%). Hospital mortality was 38.08% and significantly declined over the observation period. Mortality significantly correlated with patients’ age and was highest among individuals with (sub)acute LF (47.5%). Multivariate regression analyses revealed pulmonary (ORARDS: 2.76, ORmechanical ventilation: 6.46) and renal complications (ORacute kidney failure: 2.04, ORhepatorenal syndrome: 2.92) and sepsis (OR: 1.92) as factors for increased mortality. Liver transplantation reduced mortality in patients with (sub)acute LF. Hospital mortality significantly decreased with the annual LF case volume and ranged from 47.46% to 29.87% in low- or high-case-volume hospitals, respectively. Conclusions Although incidence rates and hospital mortality of LF in Germany have constantly decreased, hospital mortality has remained at a very high level. We identified a number of variables associated with increased mortality that could help to improve framework conditions for the treatment of LF in the future.

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“…[68] B-cell compartment abnormalities are found as the hallmark of ACLF, [96] and especially decreased proportions of memory lymphocytes [27] and higher frequencies of double-negative (DN) B cells. [96] A study use next generation sequencing (NGS) to investigate B-cell receptor (BCR) heavy chain repertoires in ACHBLF patients. They found a dramatically higher extent of clonal expansion for B cells and abnormally expressed BCR heavy chain CDR3 of the V, D, J and V-J combinations of subfamily genes in ACHBLF patients.…”

Section: B Cellsmentioning

confidence: 99%

“…B cell frequencies are decreased in ACLF patients than healthy controls and compensated cirrhosis patients [68] . B-cell compartment abnormalities are found as the hallmark of ACLF, [96] and especially decreased proportions of memory lymphocytes [27] and higher frequencies of double-negative (DN) B cells [96] . A study use next generation sequencing (NGS) to investigate B-cell receptor (BCR) heavy chain repertoires in ACHBLF patients.…”

Section: Innate Immune Cells In Achblfmentioning

confidence: 99%

Current Advances of Innate and Adaptive Immunity in Acute-on-Chronic Hepatitis B Liver Failure

Wang

Fan

2022

Infectious Diseases &Amp; Immunity

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Acute-on-chronic hepatitis B liver failure (ACHBLF) is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis. The specific pathogenesis of ACHBLF is still not completely understood. Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure (ACLF). Meanwhile, a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis. Deregulation in both the innate and adaptive immunity is the notable feature of ACLF. The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF. In this review, we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.

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B-cell compartment abnormalities are associated with ACLF and mortality in patients with liver cirrhosis

Cited by 8 publications

References 44 publications

Classification and survival prediction in early‐stage cirrhosis by gene expression profiling

Classification and survival prediction in early‐stage cirrhosis by gene expression profiling

Clinical determinants of hospital mortality in liver failure: a comprehensive analysis of 62,717 patients

Current Advances of Innate and Adaptive Immunity in Acute-on-Chronic Hepatitis B Liver Failure

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