Obesity and steatosis influence serum and hepatic inflammatory markers in chronic hepatitis C

Abstract

Obesity and fatty liver are commonly observed among patients with chronic hepatitis C virus (HCV) and are risk factors for increased hepatic fibrosis. Obesity is accompanied by a low-grade, chronic inflammatory response that may contribute to pathogenesis of obesity-related comorbidities. To assess whether obesity and steatosis potentiate expression of inflammatory markers in chronic HCV, serum protein and hepatic messenger RNA (mRNA) levels of c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured in 171 patients with chronic HCV. The relationships of body mass index, steatosis, histological features of inflammation and fibrosis with serum and hepatic levels of these factors were determined. In comparison with lean patients, overweight and obese subjects had increased circulating (P < 0.001) and hepatic (P = 0.003) CRP, and there was a significant correlation between serum protein and hepatic CRP mRNA levels (r(s)= 0.51, P < 0.001). Obesity (P = 0.001) and steatosis (P < 0.001) were associated with increased circulating but not hepatic IL-6, and a weak correlation was seen between serum protein and hepatic IL-6 mRNA levels (r(s)= 0.29, P = 0.003). An independent relationship was seen between hepatic TNF-alpha mRNA levels and higher total inflammatory score (P < 0.001) and stage of fibrosis (P = 0.037). Subjects with HCV genotype 3 had lower hepatic TNF-alpha mRNA levels compared with subjects with genotype 1 (P = 0.017), but there was no relationship between serum TNF-alpha protein and hepatic TNF-alpha mRNA levels.

Conclusion: In patients with chronic HCV, obesity and steatosis are associated with increased expression of selected inflammatory markers; however, circulating levels of IL-6 and TNF-alpha do not reflect hepatic expression. Hepatic TNF-alpha was associated with both increased inflammatory activity and hepatic fibrosis, providing support for the key role of this pro-inflammatory cytokine in liver injury in chronic HCV.