Divergences in Macrophage Activation Markers Soluble CD163 and Mannose Receptor in Patients With Non-cirrhotic and Cirrhotic Portal Hypertension

IntroductionMacrophages are involved in development and progression of chronic liver disease and portal hypertension. The macrophage activation markers soluble (s)CD163 and soluble mannose receptor (sMR), are associated with portal hypertension in patient with liver cirrhosis but never investigated in patients with non-cirrhotic portal hypertension. We hypothesized higher levels in cirrhotic patients with portal hypertension than patients with non-cirrhotic portal hypertension. We investigated sCD163 and sMR levels in patients with portal hypertension due to idiopathic portal hypertension (IPH) and portal vein thrombosis (PVT) in patients with and without cirrhosis.MethodsWe studied plasma sCD163 and sMR levels in patients with IPH (n = 26), non-cirrhotic PVT (n = 20), patients with cirrhosis without PVT (n = 31) and with PVT (n = 17), and healthy controls (n = 15).ResultsMedian sCD163 concentration was 1.51 (95% CI: 1.24–1.83) mg/L in healthy controls, 1.96 (95% CI: 1.49–2.56) in patients with non-cirrhotic PVT and 2.16 (95% CI: 1.75–2.66) in patients with IPH. There was no difference between non-cirrhotic PVT patients and healthy controls, whereas IPH patients had significantly higher levels than controls (P < 0.05). The median sCD163 was significantly higher in the cirrhotic groups compared to the other groups, with a median sCD163 of 6.31 (95% CI: 5.16–7.73) in cirrhotics without PVT and 5.19 (95% CI: 4.18–6.46) with PVT (P < 0.01, all). Similar differences were observed for sMR.ConclusionSoluble CD163 and sMR levels are elevated in patients with IPH and patients with cirrhosis, but normal in patients with non-cirrhotic PVT. This suggests that hepatic macrophage activation is more driven by the underlying liver disease with cirrhosis than portal hypertension.

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FRI-120-Structural liver disease rather than portal hypertension is the predominant factor for hepatic macrophage activation in patients with cirrhosis, portal vein thrombosis and idiopathic portal hypertension

Journal of Hepatology ◽

10.1016/s0618-8278(19)30865-5 ◽

2019 ◽

Vol 70 (1) ◽

pp. e439-e440

Author(s):

Nikolaj Worm Orntoft ◽

Michel Blé ◽

Anna Baiges ◽

Claudia Berbel ◽

Virginia Hernández-Gea ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Portal Vein ◽

Portal Vein Thrombosis ◽

Macrophage Activation ◽

Idiopathic Portal Hypertension ◽

Vein Thrombosis ◽

Predominant Factor ◽

Hepatic Macrophage

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The novel macrophage activation marker soluble Mannose Receptor, and soluble CD163, are elevated after acetaminophen intoxication in relation to liver disease severity

Journal of Hepatology ◽

10.1016/s0168-8278(17)31147-9 ◽

2017 ◽

Vol 66 (1) ◽

pp. S396-S397

Author(s):

C.B. Siggaard ◽

K. Kazankov ◽

H.J. Møller ◽

M.C. Donnelly ◽

K.J. Simpson ◽

...

Keyword(s):

Liver Disease ◽

Disease Severity ◽

Macrophage Activation ◽

Mannose Receptor ◽

The Novel ◽

Activation Marker ◽

Soluble Cd163 ◽

Acetaminophen Intoxication

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Contact System Activation and Neutrophil Extracellular Trap Markers: Risk Factors for Portal Vein Thrombosis in Patients With Hepatocellular Carcinoma

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618825310 ◽

2019 ◽

Vol 25 ◽

pp. 107602961882531 ◽

Cited By ~ 5

Author(s):

Jong Do Seo ◽

Ja-Yoon Gu ◽

Hye Soo Jung ◽

Yoon Jun Kim ◽

Hyun Kyung Kim

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Liver Disease ◽

Contact System ◽

Healthy Controls ◽

Activation Markers ◽

Thrombotic Risk ◽

Vein Thrombosis ◽

Factor Xiia ◽

System Activation

Although portal vein thrombosis (PVT) commonly occurs in patients with hepatocellular carcinoma (HCC), the hypercoagulability mechanism in patients with HCC is not entirely clear. Recently, tumor-induced formation of neutrophil extracellular traps (NET) has been shown to trigger contact system activation, and contact system activation has been shown to be a new mechanism of thrombosis. Therefore, we investigated whether contact system activation and NET formation occurred in relation to PVT in HCC patients. The circulating levels of NET formation markers (DNA–histone complex, double-stranded DNA, neutrophil elastase) and contact system activation markers (factor XIIa and high-molecular-weight kininogen) were measured in 177 patients who had been diagnosed with HCC and 48 healthy controls. Presence of PVT was confirmed in 77 HCC patients. The levels of NET formation and contact system activation markers were significantly higher in patients than in healthy controls and they increased significantly with the increase in the model for end-stage liver disease (MELD) scores. Of note, these markers were significantly higher in HCC patients with PVT than in those without PVT. These NET formation markers and the contact system activation markers were significant thrombotic risk factors in HCC patients. The well-known liver injury markers (alanine transaminase, prothrombin time) significantly contributed to factor XIIa level. Contact system activation and NET formation are well correlated with liver disease severity and the markers of these can be used as thrombotic risk factors in HCC patients. In addition, therapeutics inhibiting the contact system can be potentially used to manage PVT in HCC patients.

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Macrophage Activation Markers, Soluble CD163 and Mannose Receptor, in Liver Fibrosis

Frontiers in Medicine ◽

10.3389/fmed.2020.615599 ◽

2021 ◽

Vol 7 ◽

Author(s):

Rasmus Hvidbjerg Gantzel ◽

Mikkel Breinholt Kjær ◽

Tea Lund Laursen ◽

Konstantin Kazankov ◽

Jacob George ◽

...

Keyword(s):

Liver Diseases ◽

Macrophage Activation ◽

Mannose Receptor ◽

Host Immune System ◽

Activation Markers ◽

Soluble Cd163 ◽

Cytokines And Chemokines ◽

Essential Components ◽

Stimulation Of

Macrophages are essential components of the human host immune system, which upon activation facilitates a broad pallet of immunomodulatory events including release of pro- or anti-inflammatory cytokines and chemokines, restoration of immune homeostasis and/or wound healing. Moreover, some macrophage phenotypes are crucially involved in fibrogenesis through stimulation of myofibroblasts, while others promote fibrolysis. During the last decades, the role of resident liver macrophages viz. Kupffer cells and recruited monocytes/macrophages in acute and chronic liver diseases has gained interest and been extensively investigated. Specifically, the scavenger receptors CD163 and mannose receptor (CD206), expressed by macrophages, are of utmost interest since activation by various stimuli induce their shedding to the circulation. Thus, quantifying concentrations of these soluble biomarkers may be of promising clinical relevance in estimating the severity of inflammation and fibrosis and to predict outcomes such as survival. Here, we review the existing literature on soluble CD163 and soluble mannose receptor in liver diseases with a particular focus on their relationship to hepatic fibrosis in metabolic associated fatty liver disease, as well as in chronic hepatitis B and C.

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Development of Portal Vein Thrombosis Complicating Idiopathic Portal Hypertension

Gastroenterology ◽

10.1016/s0016-5085(85)80025-1 ◽

1985 ◽

Vol 88 (4) ◽

pp. 1034-1040 ◽

Cited By ~ 12

Author(s):

Kunihiko Ohnishi ◽

Masayuki Saito ◽

Hidetaka Terabayashi ◽

Fumio Nomura ◽

Kunio Okuda

Keyword(s):

Portal Hypertension ◽

Portal Vein ◽

Portal Vein Thrombosis ◽

Idiopathic Portal Hypertension ◽

Vein Thrombosis

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Covered TIPS versus endoscopic band ligation plus propranolol for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: a randomised controlled trial

Gut ◽

10.1136/gutjnl-2017-314634 ◽

2017 ◽

Vol 67 (12) ◽

pp. 2156-2168 ◽

Cited By ~ 38

Author(s):

Yong Lv ◽

Xingshun Qi ◽

Chuangye He ◽

Zhengyu Wang ◽

Zhanxin Yin ◽

...

Keyword(s):

Portal Hypertension ◽

Adverse Events ◽

Portal Vein ◽

Portal Vein Thrombosis ◽

Decompensated Cirrhosis ◽

Covered Stents ◽

Band Ligation ◽

Vein Thrombosis ◽

Cirrhotic Patients ◽

Endoscopic Band Ligation

ObjectiveLimited data are available on the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis (PVT). This study aimed to compare transjugular intrahepatic portosystemic shunt (TIPS) with covered stents versus endoscopic band ligation (EBL) plus propranolol for the prevention of variceal rebleeding among patients with cirrhosis and PVT.DesignConsecutive cirrhotic patients (94% Child-Pugh class A or B) with PVT who had variceal bleeding in the past 6 weeks were randomly assigned to TIPS group (n=24) or EBL plus propranolol group (EBL+drug, n=25), respectively. Primary endpoint was variceal rebleeding. Secondary endpoints included survival, overt hepatic encephalopathy (OHE), portal vein recanalisation and rethrombosis, other complications of portal hypertension and adverse events.ResultsDuring a median follow-up of 30 months in both groups, variceal rebleeding was significantly less frequent in the TIPS group (15% vs 45% at 1 year and 25% vs 50% at 2 years, respectively; HR=0.28, 95% CI 0.10 to 0.76, p=0.008), with a significantly higher portal vein recanalisation rate (95% vs 70%; p=0.03) and a relatively lower rethrombosis rate (5% vs 33%; p=0.06) compared with the EBL+drug group. There were no statistically significant differences in survival (67% vs 84%; p=0.152), OHE (25% vs 16%; p=0.440), other complications of portal hypertension and adverse events between groups.ConclusionCovered TIPS placement in patients with PVT and moderately decompensated cirrhosis was more effective than EBL combined with propranolol for the prevention of rebleeding, with a higher probability of PVT resolution without increasing the risk of OHE and adverse effects, but this benefit did not translate into improved survival.Trial registration numberClinicalTrials.gov: NCT01326949.

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P824 SOLUBLE CD163, A MACROPHAGE ACTIVATION MARKER, IS INDEPENDENTLY ASSOCIATED WITH STEATOHEPATITIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Journal of Hepatology ◽

10.1016/s0168-8278(14)60985-5 ◽

2014 ◽

Vol 60 (1) ◽

pp. S345-S346

Author(s):

K. Kazankov ◽

F. Barrera ◽

H.J. Møller ◽

H. Vilstrup ◽

J. George ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Macrophage Activation ◽

Alcoholic Fatty Liver ◽

Activation Marker ◽

Soluble Cd163 ◽

Alcoholic Fatty Liver Disease

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Portal Vein Thrombosis in a 21-Year-Old Man with Membranoproliferative Glomerulonephritis and Nephrotic Syndrome

Case Reports in Nephrology ◽

10.1155/2019/3409832 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3

Author(s):

Ilya Seleznev ◽

Dinara Jumadilova ◽

Assiya Naushabayeva ◽

Kairat Kabulbayev ◽

Gulaiym Karashasheva ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Portal Hypertension ◽

Liver Disease ◽

Kidney Disease ◽

Portal Vein ◽

Membranoproliferative Glomerulonephritis ◽

Microscopic Haematuria ◽

Vein Thrombosis ◽

Increased Risk ◽

Portosystemic Collaterals

Membranoproliferative glomerulonephritis, one of the main causes of nephrotic syndrome, is associated with a state of hypercoagulability that leads to increased risk of thrombotic events. Portosystemic collaterals may reopen due to reversal of the flow within the existing veins and be a presenting feature of thrombosis. We describe a patient who presented with large portosystemic collaterals and signs of portal hypertension and was subsequently found to be affected by membranous proliferative glomerulonephritis. Proteinuria and microscopic haematuria in a patient with signs of portal hypertension and no pre-existing liver disease should raise the suspicion of an underlying kidney disease.

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A Comparative Study of the Diagnostic and Prognostic Value of Macrophage Activation Marker Soluble CD163 and Alpha Fetoprotein in Cirrhotic Patients with Hepatitis C Virus-related Hepatocellular Carcinoma treated by Loco-Regional Therapy

QJM ◽

10.1093/qjmed/hcaa052.011 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

K A Mohamed ◽

E S Mohamed ◽

A M Hussein ◽

M H A Fouad ◽

A S Allam ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Prognostic Marker ◽

Prognostic Value ◽

Macrophage Activation ◽

Activation Marker ◽

Soluble Cd163 ◽

Cirrhotic Patients

Abstract Background hepatocellular carcinoma (HCC) shows an increasing incidence and represents the third most common cause of cancer-related death. Aim of the Work is to evaluate the diagnostic value of serum level of Macrophage activation marker soluble CD163 as a tumor marker for HCC and its prognostic value after transarterial chemo-embolization (TACE) or radiofrequency ablation (RFA), in comparison to alpha-feto protein (AFP). Patients and Methods this study was performed on 60 subjects from the outpatient Hepatology clinic and inpatient Gastroenterology and Hepatology Department at Ain Shams University Hospital. Group I includes 40 randomly selected cirrhotic patients with hepatitis C virus-related hepatocellular carcinoma (excluding BCLC class D) who underwent either RFA or TACE. Group II includes 20 patients with liver cirrhosis without hepatocellular carcinoma considered as control. Results soluble CD163 expression did not differ significantly between HCC group and liver cirrhosis group. This proves that soluble CD163 is not suitable for diagnostic use. On the other hand, soluble CD163 was associated with the severity of liver disease. Baseline soluble CD163 was significantly associated with disease progression independent of other risk factors known to be associated with an unfavorable course in HCC. Also the marked significant reduction of serum soluble CD163 levels in HCC patients subjected to either RF ablation or TACE proved that soluble CD163 may play a prognostic marker in HCC monitoring. Conclusion soluble CD163 is not suitable as a diagnostic marker for HCC but can be used as a prognostic marker for HCC.

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