Soluble CD163 and mannose receptor associate with chronic hepatitis B activity and fibrosis and decline with treatment

J Gastroenterol Hepatol. 2018 Feb;33(2):484-491. doi: 10.1111/jgh.13849.

Abstract

Background and aim: Liver macrophages are activated in chronic hepatitis B virus (CHB) infection and play a pivotal role in hepatic inflammation and fibrosis. However, their role during antiviral treatment is unclear. The soluble (s) macrophage activation markers, sCD163 and mannose receptor (sMR), are released during liver damage, and their serum levels reflect liver disease severity and portal hypertension. We aimed to investigate associations between sCD163 and sMR and histopathological activity and fibrosis and changes in sCD163, sMR, and hepatic CD163-expression following antiviral treatment in CHB patients.

Methods: We assessed Ishak histological necroinflammatory activity and fibrosis scores in liver biopsies from 254 CHB patients and serially in 71 patients before and after nucleoside-analogue treatment. Liver CD163-expression was semi-quantitatively determined by immunohistochemistry and serum sCD163 and sMR measured by enzyme-linked immunosorbent assays.

Results: Before treatment, the mean levels of sCD163 and sMR were 3.57 (SD 1.72) mg/L and 0.35 (0.12) mg/L. sCD163 and sMR increased with histological inflammatory activity (sCD163: r = 0.46, P < 0.00001; sMR: r = 0.48, P < 0.00001) and correlated positively with fibrosis (sCD163: OR 1.16, 95% CI:1.03-1.31; sMR: OR 1.34, 95% CI:1.13-1.59); both were markers of fibrosis independent of other biochemical parameters and risk factors. Antiviral treatment significantly reduced sCD163 (3.76 [1.46] vs 2.31 [0.95], P < 0.00001), sMR (0.37 [0.1] vs 0.29 [0.07], P < 0.00001) and hepatic CD163-expression (P = 0.0002).

Conclusion: The macrophage activation markers sCD163 and sMR were associated with activity and fibrosis in liver biopsies from CHB patients. Both serum markers decreased with antiviral treatment, along with decreased hepatic CD163 expression.

Keywords: antiviral treatment; fibrosis; hepatitis B; macrophages; soluble CD163; soluble mannose receptor.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / blood*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Female
  • Fibrosis
  • Hepatitis B, Chronic / diagnosis*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology
  • Humans
  • Lectins, C-Type / blood*
  • Liver / metabolism
  • Liver / pathology*
  • Macrophage Activation
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / blood*
  • Middle Aged
  • Receptors, Cell Surface / blood*
  • Receptors, Cell Surface / metabolism
  • Severity of Illness Index
  • Solubility

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antiviral Agents
  • Biomarkers
  • CD163 antigen
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface