Effects of the CCR5-Δ32 mutation on antiviral treatment in chronic hepatitis C

CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

“…This is in line with previous, substantially smaller studies that have not shown a direct effect of CCR5-∆32 on treatment response to IFN/RBV treatment [21][22][23][24][25][26][27] . As we have previously shown in a small cohort of patients, the outcome of IFN monotherapy, but not dual therapy, may be affected by CCR5-∆32 21 . The lack of a CCR5-∆32 association in that and the current cohort may be due to a RBV effect.…”

“…In order to examine if the combination of the CCR5-∆32 deletion with the IL28B SNPs, rs12979860 and rs8099917, improves prediction of treatment-induced HCV clearance, we used logistic regression modelling as previously described 14,21 . We found no evidence for any two-way interactions between either of the two IL28B SNPs individually or in combination with CCR5-∆32 for NSVR, even though both the IL28B SNPs individually were significantly associated with treatment response (Table 3).…”

“…The presence of the CCR5-∆32 deletion might result in a reduced expression of CCR5 in these patients, impairing their activation and migration to the infected liver. These mechanisms may be the reason why CCR5-∆32 deletion may be involved in spontaneous clearance and possibly in response to IFN monotherapy 21 . RBV, however, has been postulated to exploit a novel innate mechanism to potentiate the antiviral effects of IFN-α 33 which could potentially also involve a bias favouring the Th1 immune response 34 .…”

Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis

“…Indeed, several reports showed that CCR5 polymorphisms could be host genetic factors predicting anti-viral treatment success, suggesting that this chemokine rece ptor could be involved in interferon therapy response [11,30,31] . In the present paper, we did not observe any influence of the studied polymorphisms on anti-viral treatment response.…”

Haplotype-taggingRANTES gene variants influence response to antiviral therapy in chronic hepatitis C

“…3,4 Furthermore, expression of full-length HCV complementary DNA induces the expression of RANTES in hepatocyte cell lines, 5 possibly mediated through activation of nuclear factor B. 6 Interestingly, a 32-base pair deletion in the gene of the CC chemokine receptor 5 (CCR5 ⌬32), which results in decreased receptor expression, 7 has recently been linked to a negative response to interferon monotherapy in hepatitis C. 8 Because the CCR5 ligand RANTES preferentially attracts T helper 1 lymphocytes, 9 RANTES might also be associated with treatment response to antiviral therapy, which is thought to depend on a sufficient proinflammatory cytokine response. 10,11 The human RANTES gene spans 8.5 kb on chromosome 17q11-q12 and has the characteristic three exons/ two introns organization of the CC chemokine family.…”