State of the art—Artificial liver in China

Zhang, Yimin; Li, Lanjuan

doi:10.1111/aor.13448

Cited by 3 publications

(3 citation statements)

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“…The pairwise differential expression analysis illustrated that the ACLF and ACHD groups had a small number of DEGs (13), and thus they were significantly different from the other groups (>297 DEGs) (figure 1D and online supplemental tables [5][6][7][8][9][10][11][12][13][14]. Although ACHD did not manifest the clinical features of ACLF, it was transcriptionally considered a precursor stage of ACLF.…”

Section: Transcriptomic Characteristics Of Pbmcs From Patients With Hmentioning

confidence: 97%

“… 5 6 As mentioned earlier, the two largest prospective multicentre studies of ACLF to date, CANONIC and COSSH, revealed regional phenotypic specific differences in the disease aetiology and precipitating events of ACLF. 7 Nevertheless, immune cells appear to play a crucial role in ACLF; however, the ongoing processes in these cells may be different and have not been investigated in depth to date. In the present study, we aim to provide a transcriptomic-based dataset from circulating immune cells (peripheral blood mononuclear cells, PBMCs) collected at the different stages of disease progression in patients with HBV-ACLF to clarify the detailed molecular mechanisms underlying disease development and their effects on the liver tissue and prognosis of patients with HBV-ACLF, as well as to develop and validate potential biomarkers to improve the diagnosis and prognosis of HBV-ACLF.…”

Section: Introductionmentioning

confidence: 99%

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PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF

Jiang

Liang

Jiang³

et al. 2021

Gut

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ObjectiveHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics.MethodsFour hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs).ResultsThe functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis.ConclusionsThis study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

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Section: Transcriptomic Characteristics Of Pbmcs From Patients With Hmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF

Jiang

Liang

Jiang³

et al. 2021

Gut

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“…Both conditions lead to successive multiple organ dysfunction syndrome (MODS), which increases the risk of death and poor functional outcomes 4 , 5 , resulting in high short -term (28-day) mortality (15%) 6 , 7 . Generally, both syndromes possess a poor prognosis and remain a significant challenge worldwide, resulting in high mortality and placing a heavy burden on society 8 . Significant progress has been made in the care of patients with LF in recent years, attributed to earlier diagnosis of LF and improvements in supportive and therapeutic measures, reflected in improved survival rates 9 .…”

Section: Introductionmentioning

confidence: 99%

Outcomes of Multiple Organ Dysfunction Syndrome in Patients with Acute and Acute-on-Chronic Liver Failure in China: A Single Center Retrospective Cohort Study

Guo,

Yin,

Tan

et al. 2024

Preprint

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Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) pose significant threats to patient prognosis, often leading to multiple organ dysfunction syndrome (MODS), which is characterized by simultaneous dysfunction of two or more organ systems and significantly heightens the risk of mortality. Standard strategies for managing organ complications in critical illness may not always be suitable for patients with liver failure (LF).This study aims to investigate the outcomes of MODS in patients with ALF and ACLF in China, while also identifying factors influencing mortality and prognosis. We conducted a retrospective cohort study at a specialized tertiary hospital for liver diseases in Beijing, China, spanning from June 1, 2009, to May 31, 2022.Risk factors were assessed through univariate and multivariate analyses using logistic regression. Cumulative 90-day mortality rates between the ACLF and ALF groups were compared using Cox Analysis. 195 patients with ALF and 318 patients with ACLF were included in this study. The primary outcome of interest was 90-day mortality. This study enrolled a total of 513 patients. Of these, 119 patients (61%) with ALF and 140 patients (44%) with ACLF experienced MODS. Patients with ALF exhibited a higher number of organ failures compared to those with ACLF (2 vs. 1, P = 0.006). Additionally, patients with ALF demonstrated higher median admission critical illness scores.Multivariate logistic analysis indicated that GIB (OR = 3.112, 95% CI 1.4–6.916, P = 0.005), MELD-Na scores (OR = 1.079, 95% CI 1.033–1.127, P = 0.001), Age (OR = 1.056, 95% CI 1.025–1.088, P < 0.001), NLR (OR = 1.073, 95% CI 1.014–1.132, P = 0.014), ICU admission (OR = 4.319, 95% CI 1.347–13.851, P = 0.014), and Clif-SOFA (OR = 1.147, 95% CI 1.022–1.287, P = 0.02) were independent influential factors in predicting 90-day mortality, with an AUCROC of 0.881. Multivariate logistic analysis revealed that SOFA score (OR = 1.255, 95% CI 1.166–1.351, P = 0.001), GCS scores (OR = 0.674, 95% CI 0.606–0.881, P = 0.001), Age (OR = 1.048, 95% CI 1.022–1.076, P < 0.001), and ICU admission (OR = 0.258, 95% CI 0.075–0.885, P = 0.031) were independent influential factors in predicting 90-day mortality, with an AUCROC of 0.872.Cox analysis for cumulative 90-day mortality indicated that patients with ALF had higher mortality rates compared to those with ACLF (33.8% vs. 27%, P = 0.026) and compared to patients with cirrhosis ACLF and non-cirrhosis ACLF (33.8% vs. 31% vs. 25.9%, P = 0.018).Patients with ALF exhibited a higher incidence of MODS and consequently had a poorer 90-day prognosis.

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The Inhibition of Bruton Tyrosine Kinase Alleviates Acute Liver Failure via Downregulation of NLRP3 Inflammasome

Chen

Guo

et al. 2022

The Journal of Immunology

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There is no effective treatment for acute liver failure (ALF) except for an artificial liver support system (ALSS) and liver transplant. Bruton tyrosine kinase (Btk) plays important immunoregulatory roles in the inflammatory diseases, but its possible function in ALF remains to be characterized. In this study, we detected the phosphorylation level of Btk in ALF mouse liver and analyzed the protective effects of Btk inhibitor on survival rate and liver damage in ALF mouse models. We measured the expression levels of various inflammatory cytokines in the ALF mouse liver and primary human monocytes. In addition, we examined the expression of the NLRP3 inflammasome in mouse models with or without Btk inhibition. Clinically, we observed the dynamic changes of Btk expression in PBMCs of ALSS-treated patients. Our results showed that Btk was upregulated significantly in the experimental ALF mouse models and that Btk inhibition alleviated liver injury and reduced the mortality in these models. The protective effect of Btk inhibitors on ALF mice partially depended on the suppression of NLRP3 inflammasome signaling. Clinical investigations revealed that the dynamic changes of Btk expression in PBMCs could predict the effect of ALSS treatment. Our work shows that Btk inhibition is an effective therapeutic strategy for ALF. Moreover, Btk is a useful indicator to predict the therapeutic effect of ALSS on liver failure, which might have great value in clinical practice.

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State of the art—Artificial liver in China

Cited by 3 publications

References 38 publications

PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF

PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF

Outcomes of Multiple Organ Dysfunction Syndrome in Patients with Acute and Acute-on-Chronic Liver Failure in China: A Single Center Retrospective Cohort Study

The Inhibition of Bruton Tyrosine Kinase Alleviates Acute Liver Failure via Downregulation of NLRP3 Inflammasome

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