PURPOSE: Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative. Interestingly, it has been demonstrated that a combination of specific genotypes may be a more significant and powerful approach for predicting disease risk. AIM: This study is aimed at investigating the combined effect of single nucleotide polymorphism (SNP) in IL-18 (-607C/A, -137G/C), interferon (IFN)-γ (+874T/A) and IL-10 (-1082G/A) genes on cirrhosis risk in HCV-infected patients. METHODS: Seventy-seven chronic hepatitis C Tunisian subjects were included in this study. The patients were divided into two groups: the first included 31 non-cirrhotic patients, and the second included 46 liver cirrhosis patients. IL-18 genotyping was performed using the PCR amplification and the restriction fragment length polymorphism analysis (RFLP). IFN-γ and IL-10 polymorphisms were analyzed using the allele-specific PCR (AS-PCR). RESULTS: The combined high-risk genotype (IL-18 -607C/*, IL-18 -137G/*, IFN-γ +874T/*, IL-10 -1082A/A) frequency was compared between patients with and those without cirrhosis. Individuals were classified according the number of high-risk genotypes as follows: (0-2), patients with at most two high-risk genotypes; (3-4), patients with at least three of the high-risk genotypes. The logistic regression analysis showed that patients harboring 3-4 putative high-risk genotypes have a fivefold higher risk for developing cirrhosis in comparison to those harboring at most two high-risk genotypes (OR = 5.19; 95% CI = 1.49-18.05; p = 0.009). CONCLUSION: Our study showed that the co-inheritance of IL-18, IFN-γ and IL-10 specific high-risk genotypes is associated with a greater risk for liver cirrhosis.
PURPOSE:Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative. Interestingly, it has been demonstrated that a combination of specific genotypes may be a more significant and powerful approach for predicting disease risk. AIM: This study is aimed at investigating the combined effect of single nucleotide polymorphism (SNP) in IL-18 (-607C/A, -137G/C), interferon (IFN)-γ (+874T/A) and IL-10 (-1082G/A) genes on cirrhosis risk in HCV-infectedpatients. METHODS: Seventy-seven chronic hepatitis C Tunisian subjects were included in this study. The patients were divided into two groups: the first included 31 non-cirrhotic patients, and the second included 46 liver cirrhosispatients. IL-18 genotyping was performed using the PCR amplification and the restriction fragment length polymorphism analysis (RFLP). IFN-γ and IL-10 polymorphisms were analyzed using the allele-specific PCR (AS-PCR). RESULTS: The combined high-risk genotype (IL-18 -607C/*, IL-18 -137G/*, IFN-γ +874T/*, IL-10 -1082A/A) frequency was compared between patients with and those without cirrhosis. Individuals were classified according the number of high-risk genotypes as follows: (0-2), patients with at most two high-risk genotypes; (3-4), patients with at least three of the high-risk genotypes. The logistic regression analysis showed that patients harboring 3-4 putative high-risk genotypes have a fivefold higher risk for developing cirrhosis in comparison to those harboring at most two high-risk genotypes (OR = 5.19; 95% CI = 1.49-18.05; p = 0.009). CONCLUSION: Our study showed that the co-inheritance of IL-18, IFN-γ and IL-10 specific high-risk genotypes is associated with a greater risk for liver cirrhosis.
Authors: T A Fehniger; M H Shah; M J Turner; J B VanDeusen; S P Whitman; M A Cooper; K Suzuki; M Wechser; F Goodsaid; M A Caligiuri Journal: J Immunol Date: 1999-04-15 Impact factor: 5.422
Authors: G S Baroni; A Pastorelli; A Manzin; A Benedetti; L Marucci; L Solforosi; A Di Sario; E Brunelli; F Orlandi; M Clementi; G Macarri Journal: Liver Date: 1999-06
Authors: Xiao-Hong Wang; Dale M Netski; Jacquie Astemborski; Shruti H Mehta; Michael S Torbenson; David L Thomas; Stuart C Ray Journal: J Virol Date: 2007-02-28 Impact factor: 5.103
Authors: Manuela G Neuman; Jean-Pierre Benhamou; Patrick Marcellin; Dominique Valla; Izabella M Malkiewicz; Gad G Katz; Cristhian Trepo; Marc Bourliere; Ross G Cameron; Lawrence Cohen; Mary Morgan; Hemda Schmilovitz-Weiss; Ziv Ben-Ari Journal: Transl Res Date: 2007-03 Impact factor: 7.012
Authors: A Bertoletti; M M D'Elios; C Boni; M De Carli; A L Zignego; M Durazzo; G Missale; A Penna; F Fiaccadori; G Del Prete; C Ferrari Journal: Gastroenterology Date: 1997-01 Impact factor: 22.682