Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

Basili, Stefania; Carnevale, Roberto; Nocella, Cristina; Bartimoccia, Simona; Raparelli, Valeria; Talerico, Giovanni; Stefanini, Lucia; Romiti, Giulio Francesco; Perticone, Francesco; Corazza, Gino Roberto; Piscaglia, Fabio; Pietrangelo, Antonello; Violi, Francesco

doi:10.1002/hep4.1317

Cited by 65 publications

(61 citation statements)

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“…Finally, we found independent inverse correlation of MCP-1 levels in the portal and the hepatic vein and systemic albumin levels. This correlation may also be due to the fact that albumin binds MCP-1 (28,29).…”

Section: Discussionmentioning

confidence: 99%

Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

et al. 2020

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Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl 4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl 4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).Queck et al. MCP-1 in Decompensated CirrhosisConclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.

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Section: Discussionmentioning

confidence: 99%

Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

et al. 2020

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“…The impact of cfDNA and NETs in hemostasis in LC remains unstudied. Fourth, albumin (89) and bilirubin (90) act in an antioxidative manner, with potential effect on hemostasis in LC.…”

Section: Phospholipids Cell-free Dna Neutrophil Extracellular Trapsmentioning

confidence: 99%

Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis

et al. 2020

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In the setting of liver cirrhosis (LC), profound hemostatic changes occur, which affect primary hemostasis, coagulation, and fibrinolysis. They involve prohemorrhagic and prothrombotic alterations at each of these steps. Patients with cirrhosis exhibit multifactorial thrombocytopenia and in vitro thrombocytopathy, counterbalanced by increased von Willebrand factor. The resultant shift is difficult to assess, but overall these changes probably result in a rebalanced primary hemostasis. Concerning coagulation, the reduced activity of coagulation factors is counterbalanced by an increase in factor VIII (produced by liver sinusoidal endothelial cells), a decrease of the natural anticoagulants, and complex changes, including changes in circulating microparticles, cell-free DNA, and neutrophil extracellular traps. Overall, these alterations result in a procoagulant state. As for fibrinolysis, increased tissue-type and urokinase-type plasminogen activators, a relatively decreased plasminogen activator inhibitor 1, and decreased levels of thrombin-activatable fibrinolysis inhibitor and α2-antiplasmin are counterbalanced by decreased plasminogen and a decreased fibrin clot permeability. Whether and how these changes shift fibrinolysis remains to be determined. Overall, the current consensus is that in patients with cirrhosis, the hemostasis is shifted toward a procoagulant state. We review the published evidence for the concept of LC as a prothrombotic state, discuss discordant data, and highlight the impact of the underlying cause of LC on the resultant imbalance. (Hepatology 2020;71:2135-2148). Primary HemostasisChanges of primary hemostasis in patients with LC are shown in Table 1.Abbreviations: ADAMTS13, a disintegrin and metalloprotease with thrombospondin type 1 repeats 13;Hepatology, June 2020 ZERMATTEN ET AL. 2136pRoHeMoRRHagIC CHaNgeS thrombocytopenia Thrombocytopenia (platelets <150 × 10 9 /L) occurs in up to 78% (1) of patients with LC, moderate thrombocytopenia (platelets 50-75 × 10 9 /L) occurs in approximately 13%, (2) and severe thrombocytopenia (platelets <50 × 10 9 /L) occurs in 1% to 2%. (3) Decreased production and increased clearance of platelets are both involved in LC-associated thrombocytopenia ( Fig. 1). Indeed, reticulated/immature platelets and glycocalicin (proteolytic extracellular fragment of glycoprotein 1b), which are markers of platelet production, are decreased in LC. (4) However, reticulated/ immature platelet fraction and glycocalicin index, which are markers of platelet turnover, are increased in patients with LC versus healthy donors (4,5) and in thrombocytopenic versus non-thrombocytopenic patients with LC. (4,6) Moreover, the mean platelet survival is decreased in LC, (7) indicating an increased platelet turnover. Differences across LC causes are possible. Indeed, reticulated platelets are increased in hepatitis C virus (HCV)-induced LC and decreased in alcohol-induced LC and hepatitis B virus (HBV)induced LC. (5) DeCReaSeD pRoDUCtIoN oF plateletSDecreased production is due to decre...

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“…Furthermore, lower albumin levels were shown to be associated with increased risks of developing portal vein thrombosis in cirrhosis [52]. Whether similar effects may take place at a microvascular level leading to accelerated liver dysfunction remains a purely speculative hypothesis [53].…”

Section: Plos Onementioning

confidence: 99%

The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

et al. 2020

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Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm 3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cutoff value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12-76.3) and 6.8 months (95% CI 2.7-24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3

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Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

Cited by 65 publications

References 18 publications

Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis

The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

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