Obesity and Steatosis Influence Serum and Hepatic
Inflammatory Markers in Chronic Hepatitis C
Julie R. Jonsson,1Helen D. Barrie,1Peter O’Rourke,2Andrew D. Clouston,1and Elizabeth E. Powell1,3
(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 in-
flammatory 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
was a significant correlation between serum protein and hepatic CRP mRNA levels (rs?
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 (rs? 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
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 activ-
in liver injury in chronic HCV. (HEPATOLOGY 2008;48:80-87.)
diators of inflammation.1In obese subjects, this low-
grade, chronic inflammatory response is indicated by
increased plasma levels of c-reactive protein (CRP), inter-
leukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?)
and other acute phase reactants. In comparison with lean
controls, adipose tissue from obese subjects and rodent
models of obesity has increased expression of various in-
flammatory mediators and cytokines. These factors are
produced by adipocytes and by macrophages infiltrating
adipose tissue. In addition, rodent models of obesity are
accompanied by increased hepatic expression of pro-in-
flammatory cytokines, including IL-6 and TNF-?.2
Accumulating data suggest that this inflammatory re-
sponse has a causal relationship with obesity-related co-
morbidities such as insulin resistance3and cardiovascular
disease.4It has also been postulated that the increased
production of pro-inflammatory cytokines may have a
besity is often accompanied by activation of
pro-inflammatory signaling pathways that lead
to production of biochemical markers and me-
Abbreviations: BMI, body mass index; cDNA, complementary DNA; CRP, c-
reactive protein; HCV, hepatitis C virus; HOMA, homeostasis model of assessment;
IL-6, interleukin-6; mRNA, messenger RNA; qPCR, semiquantitative real-time
polymerase chain reaction; TNF-?, tumor necrosis factor-alpha.
land, Brisbane, Australia;2Cancer and Population Studies, Queensland Institute
of Medical Research, Brisbane, Australia; and the3Department of Gastroenterology
and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Received December 17, 2007; accepted February 27, 2008.
Supported by the National Health and Medical Research Council, the Queens-
land Government’s Smart State Health and Medical Research Fund, the Princess
Alexandra Hospital Research and Development Foundation, and the Sasakawa
Foundation (Royal Children’s Hospital).
Address reprint requests to: Elizabeth Powell, Department of Gastroenterology
and Hepatology, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Bris-
bane 4102, Australia.E-mail: firstname.lastname@example.org;
Copyright © 2008 by the American Association for the Study of Liver Diseases.
Published online in Wiley InterScience (www.interscience.wiley.com).
Potential conflict of interest: Nothing to report.
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