DHCR7 rs12785878, CYP2R1 rs10741657, and GC rs7041 single nucleotide polymorphisms.Results: DHCR7 GG genotype (p=0.003) and the severity of fibrosis (p=0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis.Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (p=0.03),By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023-1.089,p=0.001), low cholesterol (OR, 0.984; 95% CI, 0.974-0.994,p=0.002), high triglycerides (OR, 1.008; 95% CI, 1.002-1.015,p=0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919-0.999,p=0.04),DHCR7 GG genotype (OR, 4.222; 95% CI, p=0.03), moderate-severe steatosis (OR, 2.588; 95% CI, 1.355-4.943;p=0.004), and moderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, p=0.001).No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. Conclusion:In G1CHC patients, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.

Background: Pegylated interferons (Peg-IFN) alpha 2a and alpha 2b show different pharmacokinetic properties, that affect absorption, serum half-life and excretion.Notwithstanding, both subtypes are still used indifferently for the treatment of hepatitis C in traditional dual combination as well as with newer agents.In this study, we assessed whether standard doses of Peg-IFN alpha 2a and 2b affect in a differential manner the early HCV viral kinetics.Methods: Patients with liver biopsy-proven, HCV-RNA+, chronic active hepatitis C undergone antiviral treatment with PR between 2007 and 2011 were studied.Histology grading and staging, IL28B status and viral genotype were analysed.HCV-RNA quantitation was performed by Cobas Taqman 5 minutes before treatment start and subsequently after 48/72 hours, 7, 14 and 28 days.Results: 187 patients were studied (median age 55 yrs, males 57%, cirrhosis 29%).85 patients (45%) received Peg-IFN alpha 2a, 102 (55%) Peg-IFN alpha 2b.The two groups were homogeneous for HCV genotype and well balanced for IL28B genotype distribution (Table 1).

Our results suggest that successful translation of this approach to humans could hold promise as one strategy to protect the liver graft from becoming infected with HCV.