title: High tumor necrosis factor-α/interleukin-10 ratio is associated with hepatocellular carcinoma in patients with chronic hepatitis C.
abstract: Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk for the development of HCC increases with the severity of liver inflammation and fibrosis. The hepatic inflammation caused by HCV involves host regulatory immune response, which is mediated by cytokines with anti-viral role upon the interaction of viral polypeptides with innate and adaptive immunity. Two cytokines; tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) play key roles in the regulation of cellular immune response in HCV infection. The aim of the present study was to determine the levels of IL-10 and TNF-α, as well as the ratio of TNF-α and IL-10 serum levels in patients with HCV and HCC caused by HCV (HCC-HCV). The study included 173 patients with chronic HCV. TNF-α and IL-10 serum levels were measured by ELISA (R&D Systems, Inc.). In the present study, 54 patients presented liver mild fibrosis, 68 had severe fibrosis and 51 patients had HCC. After adjustment in the multivariate regression analysis, the following variables remained significantly associated with HCC-HCV occurrence: diabetes (p=0.012 OR 10.44 CI 1.66-65.60), IL-10 lower levels (p<0.0001 OR 0.83 CI 0.78-0.89) and TNF-α higher levels (p<0.0001 OR 1.19 CI 1.11-1.28). Individuals with HCC presented higher TNF-α/IL-10 ratio than those with fibrosis grade F4, F3 or F0+F1+F2 (p=0.0003, p<0.0001, p<0.0001, respectively). Patients with HCC were associated to higher index TNF-α/IL-10 ratio, suggesting that the unbalanced production of these cytokines may represent progression to the liver disease severity in HCV infected patients.
authors.affiliation: Universidade Federal de Pernambuco UFPE, Recife, Brazil.
authors.forename: D C B L
authors.initials: DC
authors.lastname: Aroucha
authors.forename: R F
authors.initials: RF
authors.lastname: do Carmo
authors.forename: P
authors.initials: P
authors.lastname: Moura
authors.forename: J L A
authors.initials: JL
authors.lastname: Silva
authors.forename: L R S
authors.initials: LR
authors.lastname: Vasconcelos
authors.forename: M S M
authors.initials: MS
authors.lastname: Cavalcanti
authors.forename: M T C
authors.initials: MT
authors.lastname: Muniz
authors.forename: M L
authors.initials: ML
authors.lastname: Aroucha
authors.forename: E R F
authors.initials: ER
authors.lastname: Siqueira
authors.forename: G G O M
authors.initials: GG
authors.lastname: Cahú
authors.forename: L M M B
authors.initials: LM
authors.lastname: Pereira
authors.forename: M R C D
authors.initials: MR
authors.lastname: Coêlho
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000150:complications* / Q000235:genetics; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications* / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: C508609:IL10 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10