Investigation of the factors associated with circulating soluble CD36 levels in patients with HCV-related chronic liver disease

Abstract

Background: CD36, a class B scavenger receptor, participates in the pathogenesis of metabolic dysregulation such as insulin resistance, hepatic steatosis, and atherosclerosis. Persistent hepatitis C virus (HCV) infection often evokes these metabolic abnormalities. The primary purpose of this study was to investigate the role of CD36 in the pathogenesis of insulin resistance and hepatic steatosis caused by chronic HCV infection.

Methods: Forty-five patients with HCV-related chronic liver disease (CLD-C) were enrolled in this study. CD36 expression in the liver specimen was examined by an immunohistochemical procedure. The concentrations of circulating soluble form of CD36 (sCD36) and oxLDL were determined by the enzyme-linked innunosorbent assay. Insulin resistance was estimated by the values of HOMA-IR.

Results: Moderate to extensive hepatic CD36 expression was observed in the sinusoids of all enrolled CLD-C patients. CD36-positive sinusoids appeared to be identical to Kupffer cells. The severity of CD36 expression in the hepatic sinusoids was significantly correlated with the sCD36 level in sera of patients with CLD-C. The serum sCD36 levels were significantly correlated with body mass index and serum oxLDL levels in those patients. However, the serum sCD36 concentrations were independent of the values of HOMA-IR and the severity of hepatic steatosis.

Conclusions: These data suggest that the serum sCD36 levels reflect the severity of CD36 expression on the Kupffer cells in patients with CLD-C, and that the serum sCD36 levels were associated with obesity, although the levels were independent of insulin resistance and hepatic steatosis in those patients.

Figure 1

Representative figures of the hepatic CD36 expression by an immunohistochemical staining. (a) Moderate and (b) extensive degrees of CD36 protein were observed in the sinusoids. (original magnification × 100).

Figure 2

Representative figures of dual staining with anti-CD14 and anti-CD36 in the liver specimens. (a) immunohistochemical staining with anti-CD36 (b) immunohistochemical staining with anti-CD14, (c) nuclear staining with DAPI, (d) dual staining of anti-CD14 with anti-CD36 (original magnification × 100).

Figure 3

Relationship between hepatic CD36 expression and serum sCD36 level. Mean serum sCD36 level in the group with extensive hepatic expression of CD36 was significantly higher than that in the group with moderate hepatic expression of CD36.

Figure 4

Relationship between circulating sCD36 level and BMI, serum oxLDL level, severity of hepatic steatosis, serum ALT level, HCV-genotype or load of HCV-RNA. (a,b) Serum sCD36 levels were roughly correlated with BMI or serum oxLDL levels. (c,e) Serum sCD36 levels were not associated with the severity of the hepatic steatosis or HCV-genotypes. The bars represent the maximum and minimum levels. The boxes represent the values within the 25th and 75th percentiles. The horizontal bars represent the medians. (d,f) Serum sCD36 levels were independent of serum ALT levels and loads of HCV-RNA.

Figure 5

Comparisons of serum sCD36 and oxLDL levels between patients with CLD-C and NHCs. (a) The serum sCD36 levels were significantly higher in obese patients with CLD-C than in NHCs. Obese patients also had significantly higher serum sCD36 levels than non-obese patients. (b) The serum oxLDL levels were similarly higher in obese patients than in NHCs. However, no significant difference in the serum oxLDL level was found between obese and non-obese patients.

Figure 6

Relationship between the values of HOMA-IR and serum (a) sCD 36 levels or (b) oxLDL levels in patients with CLD-C. The values of HOMA-IR were not associated with serum sCD36 and oxLDL levels.

Figure 7

Changes in the serum (a) sCD36 and (b) oxLDL levels by the antiviral treatments. Serum sCD36 and oxLDL levels tended to be decreased by antiviral treatments. The horizontal bars represent the averages.

Figure 8

Representative figure of CD36 deficiency type 2 by flow cytometry. (a) A lack of CD36 expression on the surface of peripheral platelets was observed. (b) CD36 was normally expressed on the peripheral monocytes.