CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Berres, Marie‐Luise; Asmacher, Sonja; Lehmann, Jennifer; Jansen, Christian; Görtzen, Jan; Klein, Sabine; Meyer, Carsten H.; Strunk, H.; Fimmers, Rolf; Tacke, Frank; Strassburg, Christian P.; Trautwein, Christian; Sauerbruch, Tilman; Wasmuth, Hermann E.; Trebicka, Jonel

doi:10.1016/j.jhep.2014.09.032

Cited by 60 publications

(61 citation statements)

References 38 publications

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“…Our study reveals that the increase in Pro‐C3 in all patients after TIPS insertion might be due to an increase in collagen type III synthesis associated with deterioration of liver function with changes in liver perfusion after TIPS. This has been shown several times by us and other studies 4, 22, 32, 33. However, the cutoff for survival benefit is much lower than the cutoff for the discrimination of developing acute decompensation in patients receiving TIPS.…”

Section: Discussionmentioning

confidence: 58%

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Praktiknjo

Lehmann

Nielsen

et al. 2018

Hepatology Communications

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Patients with end‐stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute‐on‐chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III plays a role in the acceleration of liver cirrhosis after AD and analyzed its formation (Pro‐C3) and degradation (matrix metalloproteinase‐degraded type III collagen [C3M]) markers in animal models and human disease. Bile duct ligation induced different stages of liver fibrosis in rats. Fibrosis development (hydroxyprolin content, sirius red staining, α‐smooth muscle actin immunohistochemistry, messenger RNA of profibrotic cytokines), necroinflammation (aminotransferases levels), fibrolysis (matrix metalloproteinase 2 expression and activity, C1M, C4M), and Pro‐C3 and C3M were analyzed 2, 3, 4, 5, and 6 weeks after bile duct ligation (n = 5 each group). In 110 patients with decompensated liver cirrhosis who underwent a transjugular intrahepatic portosystemic shunt procedure for AD, clinical and laboratory parameters as well as Pro‐C3 and C3M were measured in blood samples from portal and hepatic veins and were collected just before the transjugular intrahepatic portosystemic shunt placement and 1‐3 weeks later. Animal studies showed increased markers of collagen type III deposition with fibrosis, necroinflammation, and decompensation of liver cirrhosis, defined as ascites development. Higher Pro‐C3 levels were associated with injury, disease severity scores (Model for End‐Stage Liver Disease, Child‐Pugh, chronic liver failure‐C AD), ACLF development, and mortality. C3M decreased with AD and the chronic liver failure‐C AD score. Collagen type III deposition ratio increased with the risk of ACLF development and mortality. Conclusion: We show for the first time that AD boosts collagen type III deposition in experimental and human cirrhosis, possibly contributing to the worsened outcome in patients with decompensated cirrhosis. (Hepatology Communications 2018;2:211–222)

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Section: Discussionmentioning

confidence: 58%

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Praktiknjo

Lehmann

Nielsen

et al. 2018

Hepatology Communications

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“…On the other hand, ascites formation, induced by PHT, seems to be another pathogenic condition of bacterial translocation. Bacterial translocation is of relevance as it is considered one -if not the most -important trigger of AD and ACLF, as it leads to continuous activation of the immune system and chronic systemic inflammation [14][15][16][17].…”

Section: Portal Hypertension and Acute Decompensationmentioning

confidence: 99%

“…Indeed, PHT predisposes and predicts survival in cirrhotic patients. However, while serum biomarkers of chronic inflammation will decrease in most patients after successful TIPS treatment of PHT, these proinflammatory biomarkers remain of independent predictive value for subsequent mortality in cirrhotic patients -even after successful lowering of the portal pressure by TIPS [17,30]. Thus, cirrhotic PHT predisposes to ACLF directly through hemodynamic derangements and indirectly through its complications.…”

Section: Portal Hypertension and Acute Decompensationmentioning

confidence: 99%

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

2018

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Acute-on-chronic liver failure (ACLF) is considered a distinct syndrome in patients with liver disease, with systemic inflammation playing a central role. Portal hypertension (PHT) is also aggravated by inflammation and may subsequently impact the course of ACLF. PHT is more than just an increase in portal pressure in the portal venous system; it aggravates the course of liver disease and, thus, also facilitates the development of acute decompensation and ACLF. A critical mechanistic link between PHT and ACLF might be the gut-liver axis, which is discussed in this review.

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“…Up-regulation of these chemokines are known to predict a worse prognosis in patients with various chronic liver diseases [12][13][14][15][16], such as viral hepatitis [13,18,20,31], alcoholic hepatitis or non-alcoholic steatohepatitis [19], liver transplantation [33], autoimmune hepatitis [34], liver cirrhosis [12,17], and so on. These studies revealed that the serum and intrahepatic levels of these chemokines are increased during liver injury, and therefore contributing to the development of clinically hepatic disease [7,[12][13][14][15][16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…The high levels of CXCL9-11 have been found to be independently related to the development of clinically hepatic disease [15,16]. According to some studies, elevated serum and intrahepatic CXCL9 and CXCL10 expression levels have been reported as important prognostic and predictive biomarkers of progressive liver injury [17][18][19][20], CXCL11, which is also expressed by hepatocytes, involves in pro-inflammatory T cells recruitment and differentiation [7]. Therefore, IFN-γ inducible chemokines have been reported as targets in anti-inflammatory therapy [21].…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Interferon-γ-Inducible Genes Expression in Hepatocytes through Down-Regulating Activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK and PI3K/Akt Signaling Pathways

Wu¹,

Xue²,

Yang³

et al. 2015

Cell Physiol Biochem

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Background & Aims: The high expression levels of interferon-γ (IFN-γ)-inducible genes correlate positively with liver diseases. The present study aimed to explore the effect of isoliquiritigenin (ISL) on the expression of genes induced by IFN-γ in vitro, and to elucidate the underlying molecular mechanisms. Methods: HepG2 and L02 cells were divided into control, ISL, IFN-γ, and IFN-γ plus ISL groups. The cytotoxicity of compounds to cells was evaluated by Cell Counting Kit 8 (CCK8) assay; the expression levels of chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, CXCL11, and interleukin-6 (IL-6) in cells and supernatant were measured by quantitative real time polymerase chain reaction (qRT-PCR) and ELISA, respectively. Moreover, western blot was used to examine the phosphorylated levels of janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1), nuclear factor (NF)-γB, interferon regulatory factor 3 (IRF3)/myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (Akt) in HepG2 and L02 cells exposed to ISL, IFN-γ and IFN-γ plus ISL. Results: The results showed that IFN-γ treatment induced the expression of CXCL9, CXCL10, CXCL11, and IL-6 in HepG2 and LO2 cells, which could be significantly and dose-dependently inhibited by ISL treatment (P < 0.05 or P < 0.01), but the inhibitory effect of ISL on IL-6 expression was not so good as on CXCL9, CXCL10, and CXCL11 expression. Furthermore, ISL treatment dose-dependently inhibited the activation of JAK1/STAT1, IRF3/MyD88, extracellular signal-regulated kinase (ERK)/MAPK, c-Jun N-terminal kinase (JNK)/MAPK, and PI3K/Akt signaling pathways (P < 0.05), but had no effect on the activation of JAK2/STAT1, NF-γB and p38/MAPK signaling pathways. Conclusion: We demonstrate that ISL inhibits IFN-γ-induced inflammation in hepatocytes via influencing the activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK, and PI3K/Akt signaling pathways.

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CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Cited by 60 publications

References 38 publications

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

Isoliquiritigenin Inhibits Interferon-γ-Inducible Genes Expression in Hepatocytes through Down-Regulating Activation of JAK1/STAT1, IRF3/MyD88, ERK/MAPK, JNK/MAPK and PI3K/Akt Signaling Pathways

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