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IL28B -3176(C/T)

The combined therapy with pegylated interferon (PegIFN-alpha-2a) and ribavirin (RBV) is the current standard for the treatment of chronic HCV infections, but its outcome is influenced by a number of factors including the viral genotype and certain genetic polymorphisms of the host. Patients infected with HCV genotype 2 or 3 have 2-3 times more likely to respond to interferon-based therapy compared with those who are infected with genotype 1. One SNP in the promoter sequence (position -3176 C / T) upstream of the human gene (IL28B) that encodes for the protein Interferon-λ-3 (rs12979860), located on chromosome 19 (19q13.13), whose expression is induced and activated by viral infection, appears to be strongly associated with sustained virological response (SVR) in all groups of patients. In addition, some studies indicate that this genetic polymorphism is strongly associated with a greater probability of a spontaneous clearance (elimination) as a result of a viral acute HCV infection.

The CC genotype is associated with a value of two to three times higher SVR compared to the TT genotype in the Caucasian-American population and African-Americans and Hispanics groups, and it seems plausible that the IL28B polymorphism has a role in the expression of the gene stimulated intra-hepatic by IFN, with consequences for both the viral load, which for the response to drug treatment. The test allows the differentiation of the following genotypes: homozygous (C / C), heterozygous (C / T), homozygous (T / T) for possible use at the clinical level to customize and optimize the administration of anti-HCV. Polymorphism not only strongly influences the response within each of the main groups of the population, but also seems to explain many of the differences in treatment response between different population groups (European-Americans than African-Americans) as a function of frequency.

In addition, there was a higher frequency of C in patients from East Asia. In conclusion, the genetic polymorphism rs12979860 seems to be the most suitable predictive marker of the outcome of anti-HCV potentially allowing to divide the patients into two groups: one with a genotype favorable response to standard therapy, which must be customized for duration, and the one with less favorable genotype in the response that the decision to give the standard of care should be evaluated on the basis also of the potential use of antiviral drugs emerging.

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