Article

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

School of Medicine, Southern Clinical Division, University of Queensland, Brisbane, Australia.
Hepatology (Impact Factor: 11.06). 07/2008; 48(1):80-7. DOI: 10.1002/hep.22311
Source: PubMed

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.

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    • "Our study confirmed that the GG genotype of the TNF-α −238 gene promoter is implicated in the probability of liver cirrhosis, supporting our previous data [19] in a different and larger sample of HIV/HCV coinfected patients. Previous data have demonstrated the impact of TNF-α on liver fibrogenesis: increased concentrations of TNF-α have been detected in the liver of patients with chronic hepatitis C [45] and it has been observed that serum levels of this cytokine are correlated with the histological grading score of hepatitis [46]. Likewise, it has been observed that patients with increased serum levels of TNF-α or its receptors showed a reduced survival rate [47]. "
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    ABSTRACT: Objective To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism). Patients and Methods A sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, −238 TNF-α and −592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count. Results Patients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of −238 TNF-α genotype GG was detected in patients with significant liver fibrosis. Conclusions In HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a −238 TNF-α polymorphism in these patients.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "TNF-α can potentially affect liver fibrogenesis by stimulating hepatic stellate cells [9]. The pathogenic importance of TNF-α in liver disease has been previously demonstrated: besides the increased concentration of TNF-α in the liver of patients with chronic hepatitis C [10], it has been observed that serum levels of this cytokine are correlated with histological grading score of hepatitis [11]; moreover, patients with increased serum levels of TNF-α or their receptors showed a reduced survival [12]. "
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    Full-text · Article · Jun 2013 · PLoS ONE
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    • "Nonresponders were described as patients with a decrease less than 2 log in HCV RNA levels at the 12th week. Also patients with positive HCV RNA at the 24th week were accepted as nonresponders; treatment was continued up to 48th week for patients with negative HCV RNA at the 24th week.10-12 "
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