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.