Soluble CD163 and mannose receptor as markers of liver disease severity and prognosis in patients with primary biliary cholangitis

Bossen, Lars; Rebora, Paola; Bernuzzi, Francesca; Jepsen, Peter; Gerussi, Alessio; Andreone, Pietro; Galli, Andrea; Terziroli, Benedetta; Alvaro, Domenico; Labbadia, Giancarlo; Aloise, Chiara; Baiocchi, Leonardo; Giannini, Edoardo G.; Abenavoli, Ludovico; Toniutto, Pierluigi; Marra, Fabio; Marzioni, Marco; Niro, G.A.; Floreani, Annarosa; Møller, Holger Jon; Valsecchi, Maria Grazia; Carbone, Marco; Grønbæk, Henning; Invernizzi, Pietro

doi:10.1111/liv.14466

Cited by 23 publications

(20 citation statements)

References 32 publications

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“…Further, a dual CCR2/CCR5 antagonist (cenicriviroc) treatment improves fibrosis and inflammation in the liver in PBC mouse model. Serum macrophage activation markers, soluble CD163 and mannose receptor, are reported to be biomarkers of severity and prognosis in patients with PBC [53]. Taken together, the results of these reports suggest the important roles of macrophages and monocytes in patients with PBC.…”

Section: Discussionmentioning

confidence: 72%

Association between serum ficolin-1 level and disease progression in primary biliary cholangitis

et al. 2020

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Pattern recognition molecules (PRMs) in the complement system contribute to homeostasis as mediators of complement activation. The contribution of PRMs to primary biliary cholangitis (PBC) is unknown. In the current study, we aimed to assess the association between PRMs and the clinical findings of PBC. A total of 122 PBC patients and 20 healthy controls were enrolled. We measured four different PRMs (mannose-binding lectin [MBL], ficolin-1, ficolin-2 and ficolin-3) using stored sera, and retrospectively analyzed the associations between PRMs and laboratory findings, histological findings, and the development of cirrhosis-related conditions. Ficolin-1 levels were significantly higher in the PBC patients than in the healthy controls (152 ng/mL vs 102 ng/mL, P = 0.034), but no significant differences were observed regarding MBL, ficolin-2, and ficolin-3 levels. Ficolin-1 was significantly correlated with alkaline phosphatase (ALP). Low ficolin-1 levels were significantly associated with the development of cirrhosis-related conditions independent for histological stage and ALP levels (hazard ratio: 0.933; 95% confidence interval: 0.875-0.994; P = 0.032). Patients with low levels of ficolin-1 (< 77 ng/mL) had a significantly increased rate of developing cirrhosis-related conditions. Low ficolin-1 levels were associated with disease progression independent of histological stage and ALP levels in patients with PBC.

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Section: Discussionmentioning

confidence: 72%

Association between serum ficolin-1 level and disease progression in primary biliary cholangitis

et al. 2020

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“…Macrophage activation, as measured by sCD163, is associated with liver fibrosis and cirrhosis, liver disease severity (Child-Pugh-and MELD scores), and portal hypertension (Holland-Fischer et al, 2011;Gronbaek et al, 2012;Rode et al, 2013;Kazankov et al, 2014Kazankov et al, , 2015Kazankov et al, , 2016Grønbaek et al, 2020). Furthermore, sCD163 levels are associated with prognosis, predict the risk of variceal bleeding (Rode et al, 2013;Waidmann et al, 2013) and correlates to disease severity and treatment response in patients with non-alcoholic fatty liver disease (Kazankov et al, 2015), alcoholic hepatitis (Sandahl et al, 2014), hepatitis B and C virus infection (Dultz et al, 2015;Laursen et al, 2018Laursen et al, , 2019 and autoimmune liver diseases (Gronbaek et al, 2016a;Bossen et al, 2020Bossen et al, , 2021. The magnitude of macrophage activation and corresponding elevated plasma markers depends on the underlying pathogenesis, being more pronounced in conditions with a high hepatic inflammatory load and fibrosis like acute liver failure and advanced cirrhosis (Hiraoka et al, 2005;Moller et al, 2007;Gronbaek et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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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“…In this review, when discussing nonalcoholic fatty liver disease (NAFLD), we will use the recently introduced and more appropriate consensus nomenclature of metabolic associated fatty liver disease (MAFLD) (35,36). As previously summarized and illustrated in (22,37,38) plasma levels of sCD163 are moderately elevated in MAFLD (39), chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections (40), Wilson's disease (41,42), and primary biliary cholangitis (43), and clearly reflects disease severity in MAFLD, HBV and HCV (39,40,(44)(45)(46)(47). In further support of a correlation between sCD163 concentrations and liver disease severity sCD163 levels show significant reductions after lifestyle interventions in MAFLD (48,49) and after antiviral therapy in HBV and HCV (46,50,51).…”

Section: Macrophage Activation Markers In Liver Diseasesmentioning

confidence: 99%

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

et al. 2021

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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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Soluble CD163 and mannose receptor as markers of liver disease severity and prognosis in patients with primary biliary cholangitis

Cited by 23 publications

References 32 publications

Association between serum ficolin-1 level and disease progression in primary biliary cholangitis

Association between serum ficolin-1 level and disease progression in primary biliary cholangitis

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

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

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