Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery.

Abstract

Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS). Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS < 5 (2.4(2.0-3.1) vs 1.9(1.5-2.3) mg/L, P < 0.001) and in patients with bridging fibrosis (F ≥ 3) compared with lower fibrosis stages (2.6(2.0-4.9) vs 2.0(1.5-2.4) mg/L, P = 0.001). Preoperative sCD163 was independently associated with both the NAS (P = 0.002) and the fibrosis score (P = 0.024). sCD163 decreased after BS and was greatly reduced after 12 months, more rapidly so in patients with NAS ≥ 5 (P < 0.001) and non-alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P = 0.03). Immunohistochemistry showed CD163-positive macrophages aligning fat-laden hepatocytes and forming microgranulomas in patients with NASH. CD163 mRNA expression did not vary with NAS. sCD163 increased in parallel with the severity of NAFLD in morbid obesity, indicating macrophage activation. BS reduced sCD163 even in patients with severe liver injury and fibrosis, suggesting full reversibility of macrophage activation associated with improved insulin sensitivity.