Single-centre experience of the macrophage activation marker soluble (s)CD163 - associations with disease activity and treatment response in patients with autoimmune hepatitis

Aliment Pharmacol Ther. 2016 Nov;44(10):1062-1070. doi: 10.1111/apt.13801. Epub 2016 Sep 28.

Abstract

Background: Autoimmune hepatitis (AIH) is characterised by liver inflammation with reversibility upon anti-inflammatory treatment. Soluble (s)CD163, a specific macrophage activation marker, is associated with inflammation in other liver diseases, but never investigated in AIH.

Aim: To investigate sCD163 in patients with acute AIH and in complete and incomplete responders to standard anti-inflammatory pharmacotherapy, and during follow-up in treatment naive patients.

Methods: In a cross-sectional design, we studied 121 AIH patients (female/male 89/32, median age 49 years); of these, we prospectively studied 10 treatment naïve AIH patients during prednisolone treatment and tapering. Twenty patients had variant syndromes of AIH and primary biliary cholangitis or primary sclerosing cholangitis. sCD163 was compared with markers of disease activity, severity and treatment response.

Results: In the patients with acute AIH (n = 21), sCD163 was sixfold increased compared with the normalised levels in patients (n = 32) with complete response to standard treatment [9.5 (3.3-28.8) vs. 1.6 (0.8-3.2) mg/L, P < 0.01)], while the patients (n = 27) with incomplete response had higher sCD163 [2.2 (1.3-7.9), P < 0.05] than the complete responders. sCD163 was positively associated with ALAT, IgG and bilirubin (rho: 0.45-0.59, P < 0.001, all), and negatively to external coagulation factors (rho:-0.34, P < 0.001). In the treatment naïve patients, sCD163 fell during high-dose prednisolone treatment and tapering. Immunohistochemical staining confirmed increased CD163 expression in liver biopsies from patients with acute AIH.

Conclusions: sCD163 was markedly elevated in AIH in the acute phase, normalised by successful treatment in complete responders, but remained higher in the incompletely responding cases. Our results demonstrate macrophage activation in AIH paralleling disease activity, severity and treatment response, suggesting a role for macrophage activation in AIH.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Biomarkers / blood
  • Cholangitis, Sclerosing / blood
  • Cholangitis, Sclerosing / drug therapy
  • Cross-Sectional Studies
  • Female
  • Glucocorticoids / therapeutic use
  • Hepatitis, Autoimmune / blood*
  • Hepatitis, Autoimmune / drug therapy
  • Humans
  • Macrophage Activation
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Receptors, Cell Surface / blood*
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • Glucocorticoids
  • Receptors, Cell Surface
  • Prednisolone