scholarly journals Transcriptomics reveals immune-metabolism disorder in acute-on-chronic liver failure in rats

2021 ◽  
Vol 5 (3) ◽  
pp. e202101189
Author(s):  
Hozeifa M Hassan ◽  
Qun Cai ◽  
Xi Liang ◽  
Jiaojiao Xin ◽  
Keke Ren ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Failure ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Clinical Syndrome ◽  
Chronic Liver ◽  
Differentially Expressed ◽  
Chronic Liver Failure ◽  
Porcine Serum ◽  
Metabolism Disorder

Acute-on-chronic liver failure (ACLF) is clinical syndrome with high mortality rate. This study aimed to perform detailed transcriptomic analysis in liver cirrhosis–based ACLF rats to elucidate ACLF pathogenesis. ACLF was induced by combined porcine serum with D-galactosamine and lipopolysaccharide. Gene expression profile of liver tissues from ACLF rats was generated by transcriptome sequencing to reveal the molecular mechanism. ACLF rats successfully developed with typical characteristics. Total of 2,354/3,576 differentially expressed genes were identified when ACLF was compared to liver cirrhosis and normal control, separately. The functional synergy analysis revealed prominent immune dysregulation at ACLF stage, whereas metabolic disruption was significantly down-regulated. Relative proportions of innate immune–related cells showed significant elevation of monocytes and macrophages, whereas adaptive immune–related cells were reduced. The seven differentially expressed genes underlying the ACLF molecular mechanisms were externally validated, among them THBS1, IL-10, and NR4A3 expressions were confirmed in rats, patient transcriptomics, and liver biopsies, verifying their potential value in the ACLF pathogenesis. This study indicates immune-metabolism disorder in ACLF rats, which may provide clinicians new targets for improving intervention strategies.

Serum cholinesterase, an underestimated marker in the prediction of acute-on-chronic liver failure, organ failure and LTx-free survival in patients with liver cirrhosis?

2020 ◽  
Vol 73 ◽  
pp. S504
Author(s):  
Tammo Lambert Tergast ◽  
Abdul-Rahman Kabbani ◽  
Marie Schultalbers ◽  
Michael P. Manns ◽  
Markus Cornberg ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Failure ◽  
Organ Failure ◽  
Chronic Liver ◽  
Serum Cholinesterase ◽  
Chronic Liver Failure ◽  
Free Survival

scholarly journals Dysregulated Adaptive Immunity Is an Early Event in Liver Cirrhosis Preceding Acute-on-Chronic Liver Failure

2021 ◽  
Vol 11 ◽  
Author(s):  
Sabrina Rueschenbaum ◽  
Sandra Ciesek ◽  
Alexander Queck ◽  
Marek Widera ◽  
Katharina Schwarzkopf ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Cirrhosis ◽  
Liver Failure ◽  
Cd8 T Cells ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Decompensated Liver Cirrhosis ◽  
Tt Virus ◽  
Adaptive Immune ◽  
Acute Decompensation

IntroductionAcute-on-chronic liver failure (ACLF) is characterized by high levels of systemic inflammation and parallel suppression of innate immunity, whereas little is known about adaptive immune immunity in ACLF. We therefore aimed to characterize the development of the adaptive immune system during the progression of liver cirrhosis to ACLF. Patients with compensated/stable decompensated liver cirrhosis, acute decompensation of liver cirrhosis, or ACLF were recruited from a prospective cohort study. Comprehensive immunophenotyping was performed using high dimensional flow cytometry. Replication of Torque teno (TT) virus was quantified as a marker of immunosuppression. High frequencies of detectable TT virus were observed already in patients with compensated/stable decompensated liver cirrhosis compared to healthy controls (>50% vs. 19%), suggesting relatively early occurrence of immunosuppression in cirrhosis. In line, profoundly reduced numbers of distinct innate and adaptive immune cell populations were observed before ACLF development. These changes were accompanied by parallel upregulation of co-stimulatory (e.g. CD40L, OX40, CD69, GITR, TIM-1) and inhibitory immune checkpoints (e.g. PDPN, PROCR, 2B4, TIGIT) on CD4+ and CD8+ T cells, which again preceded the development of ACLF. On a functional basis, the capacity of CD4+ and CD8+ T cells to produce pro-inflammatory cytokines upon stimulation was strongly diminished in patients with acute decompensation of liver cirrhosis and ACLF.ConclusionImpaired innate and—in particular—adaptive cellular immunity occurs relatively early in the pathogenesis of liver cirrhosis and precedes ACLF. This may contribute to the development of ACLF by increasing the risk of infections in patients with liver cirrhosis.

scholarly journals Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival

Critical Care ◽  
2017 ◽  
Vol 21 (1) ◽  
Author(s):  
Annarein J. C. Kerbert ◽  
◽  
Hein W. Verspaget ◽  
Àlex Amorós Navarro ◽  
Rajiv Jalan ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Term Survival ◽  
Acute Decompensation ◽  
Short Term Survival
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