Thus, the prediction
of the rate of disease progression at an individual level is still quite inaccurate, often making impossible the selection of patients selleckchem for anti-HCV treatment on the basis of the risk to progress to the advanced stages of hepatitis. Some evidences exist on the role of host genetics in modifying disease progression, because several single-nucleotide polymorphisms (SNPs) located in various genes, including interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β), among others, have been associated with progression of liver fibrosis.2 A recent article supported these findings, providing evidence that a seven-SNP signature was associated with fibrosis progression in a large cohort of HCV-infected patients in Italy.5 Among the SNPs identified to play a major role in HCV infection, those located in the IL28B region on chromosome 19 have been strongly associated with spontaneous and treatment-induced viral clearance in patients of different ethnicity.6-10 Thus, patients
with the T/T and C/T genotype at the rs12979860 SNP (nonresponder genotype) have been shown to exhibit a slower viral decline after pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, with the sustained virologic response (SVR) rates being significantly lower, compared to patients with the favorable C/C genotype.11 Although this discovery has radically changed the landscape of antiviral treatment for HCV patients, providing insights into the mechanisms of IFN hyporesponsiveness, the
precise mechanisms behind PD332991 this association still needs to be unraveled. In addition, whether there is a link between the clinical manifestation of chronic HCV infection and oxyclozanide the patient IL28B genotype is still an open question. Here, we asked whether a correlation between IL28B SNPs and fibrosis progression exists. To test this hypothesis, we studied 247 consecutive patients with a known date of HCV infection, whose liver fibrosis was staged by a percutaneous liver biopsy. We studied the effect of host and external factors on both fibrosis progression rate and advanced fibrosis stage. ALT, alanine aminotransferase; BMI, body mass index; CI, confidence interval; EDTA, ethylenediaminetetraacetic acid; FPR, fibrosis progression rate; gDNA, genomic DNA; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN-γ, interferon gamma; IL28B, interleukin-28B; PEG-IFN/RBV, pegylated interferon plus ribavirin; SNPs, single-nucleotide polymorphisms; SVR, sustained virologic response; TGF-β, transforming growth factor beta; TNFα, tumor necrosis factor alpha. A total of 247 participants with chronic HCV infection were included in this study. All participants were consecutively selected at the Center for Liver Disease at Maggiore Hospital (Milan, Italy).