Dataset Information

The soluble mannose receptor (sMR) is elevated in alcoholic liver disease and associated with disease severity, portal hypertension, and mortality in cirrhosis patients.

ABSTRACT:

Background and aims

Hepatic macrophages (Kupffer cells) are involved in the immunopathology of alcoholic liver disease (ALD). The mannose receptor (MR, CD206), expressed primarily by macrophages, mediates endocytosis, antigen presentation and T-cell activation. A soluble form, sMR, has recently been identified in humans. We aimed to study plasma sMR levels and its correlation with disease severity and survival in ALD patients.

Methods

We included 50 patients with alcoholic hepatitis (AH), 68 alcoholic cirrhosis (AC) patients (Child-Pugh A (23), B (24), C (21)), and 21 healthy controls (HC). Liver status was described by the Glasgow Alcoholic Hepatitis Score (GAHS), Child-Pugh (CP) and MELD-scores, and in AC patients the hepatic venous pressure gradient (HVPG) was measured by liver vein catheterisation. We used Kaplan-Meier statistics for short-term survival (84-days) in AH patients and long-term (4 years) in AC patients. We measured plasma sMR by ELISA.

Results

Median sMR concentrations were significantly elevated in AH 1.32(IQR:0.69) and AC 0.46(0.5) compared to HC 0.2(0.06) mg/L; p<0.001 and increased in a stepwise manner with the CP-score (p<0.001). In AC sMR predicted portal hypertension (HVPG ≥10 mmHg) with an area under the Receiver Operator Characteristics curve of 0.86 and a high sMR cut-off (>0.43 mg/l) was associated with increased mortality (p = 0.005).

Conclusion

The soluble mannose receptor is elevated in alcoholic liver disease, especially in patients with AH. Its blood level predicts portal hypertension and long-term mortality in AC patients.

SUBMITTER: Sandahl TD

PROVIDER: S-EPMC5728513 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

The soluble mannose receptor (sMR) is elevated in alcoholic liver disease and associated with disease severity, portal hypertension, and mortality in cirrhosis patients.

Sandahl Thomas Damgaard TD Støy Sidsel Hyldgaard SH Laursen Tea Lund TL Rødgaard-Hansen Sidsel S Møller Holger Jon HJ Møller Søren S Vilstrup Hendrik H Grønbæk Henning H

PloS one 20171213 12

<h4>Background and aims</h4>Hepatic macrophages (Kupffer cells) are involved in the immunopathology of alcoholic liver disease (ALD). The mannose receptor (MR, CD206), expressed primarily by macrophages, mediates endocytosis, antigen presentation and T-cell activation. A soluble form, sMR, has recently been identified in humans. We aimed to study plasma sMR levels and its correlation with disease severity and survival in ALD patients.<h4>Methods</h4>We included 50 patients with alcoholic hepatit ...[more]

PMID: 29236785

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Project description:Background and aimsThe liver plays a key role in the storage, metabolism and homeostasis of fat-soluble vitamins. We investigated the relation of Vitamin(Vit)A/D/E serum levels with severity of liver disease and portal hypertension (PHT).MethodsVitA/D/E serum levels were assessed in 234 patients with advanced chronic liver disease (ACLD, i.e. hepatic venous pressure gradient [HVPG] ≥ 6 mmHg). Patients with hepatocellular carcinoma, pre-/post-hepatic PHT, TIPS or liver transplantation were excluded.ResultsMost patients were male (n = 153; 65%) with a median age of 57.6 (49.7-64.5) years. Thirty-two (14%) patients had HVPG 6-9 mmHg, 66 (28%) 10-15 mmHg, and 136 (58%) ≥ 16 mmHg, respectively. VitD deficiency (25-OH-vitamin-D <50 nmol/L) was found in 133 (57%) with higher prevalence in Child-Turcotte-Pugh (CTP)-C: 85% vs. B: 66% vs. A: 47% (p < 0.001). VitD levels displayed significant but weak correlations with hepatic dysfunction and PHT. VitE levels were normal in 227 (97%) patients and displayed no relevant association with hepatic dysfunction or PHT. Only 63 (27%) patients had normal (>1.05 µmol/L) VitA levels, while 58 (25%) had mild (0.70-1.04 µmol/L), 71 (30%) moderate (0.35-0.69 µmol/L), and 42(18%) severe(<0.35 µmol/L) VitA deficiency. VitA correlated with HVPG (Rho = -0.409), CTP score (Rho = -0.646), and serum bile acid levels (Rho = -0.531; all p < 0.001). The prevalence of decompensated ACLD (dACLD) continuously increased with severity of VitA deficiency (no: 40% vs. mild: 51% vs. moderate: 67% vs. severe: 91% had dACLD; p < 0.001). CTP score (per point; OR 2.46; 95%CI 1.80-3.37; p <0.001), age (per year; OR 0.95; 95%CI 0.92-0.98; p = 0.001) and elevated bile acid levels(>10 µmol/L; OR 3.62; 95%CI 1.61-8.14; p = 0.002) were independently associated with VitA deficiency.ConclusionVitA and VitD but not VitE deficiencies are highly prevalent in ACLD. VitA deficiency strongly correlates with hepatic dysfunction, PHT and bile acid levels and is associated with decompensated ACLD.Trial registration numberNCT03267615.

Dataset Information

The soluble mannose receptor (sMR) is elevated in alcoholic liver disease and associated with disease severity, portal hypertension, and mortality in cirrhosis patients.

Background and aims

Methods

Results

Conclusion

Publications

The soluble mannose receptor (sMR) is elevated in alcoholic liver disease and associated with disease severity, portal hypertension, and mortality in cirrhosis patients.

Similar Datasets

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