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 obesityrelated 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-␣) 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-␣ 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-␣ mRNA levels compared with subjects with genotype 1 (P ‫؍‬ 0.017), but there was no relationship between serum TNF-␣ protein and hepatic TNF-␣ 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-␣ do not reflect hepatic expression. Hepatic TNF-␣ 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. (HEPATOLOGY 2008;48:80-87.)

Potential Role of Leptin, Adiponectin and Three Novel Adipokines—Visfatin, Chemerin and Vaspin—in Chronic Hepatitis

“…Petit et al (137) found a correlation between serum adiponectin concentration and hepatic steatosis, but in the study by Jonsson et al (139), such a relationship was found only in men with CHC. In the study by Durente-Mangoni et al (140), hypoadioponectinemia in CHC was associated with the grade of hepatic steatosis, and a changed balance between adiponectin and TNFα was suggested.…”

“…TNFα is a proinflammatory cytokine/adipokine that is elevated and positively associated with the inflammatory activity grade and fibrosis stage in CHC (47,48). Visfatin increases TNFα production in human peripheral blood mononuclear cells and in murine liver hepatocytes (25).…”

“…Alongside the direct effect of the virus, TNFα and IL-6 play an important role in IR development. Levels of both of these agents are significantly increased in CHC (47,48). The ability of visfatin to induce their synthesis might suggest its adverse effect on insulin sensitivity (25).…”

A Comparative Analysis of Serum Lipids in Patients with Chronic Hepatitis C, Nonalcoholic Fatty Liver Disease and Healthy Controls

“…The high prevalence of IR in CHC with steatosis has been reported to be due to the HCV infection and NAS independently or together [14]. Increased levels of proinfl ammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with CHC and visceral obesity also contribute to development of liver steatosis and IR [15]. A metaanalysis has shown that CHC patients have about 1.7-fold increased risk of development type 2 DM compared with noninfected controls [16].…”

Development and Evaluation of Nano‑scale Systems for Targeted Delivery to Treat Liver Fibrosis

“…Many studies have shown various cytokines, which are crucial indicators of inflammation, such as TGF-β1 and TNF-α, are very important activators during the process of liver fibrosis. [253][254][255] TNF-α has been reported closely related to liver fibrosis and cirrhosis. 255 We investigated the level of TNF-α after we treated HSCs with TGF-β1 shRNA.…”