A total cohort consisting of 731 Spanish individuals were included in this study. They were selected by using surnames and by having grandparents born in Spain. This cohort included 284 subjects

with persistent infection, 69 individuals who naturally cleared the virus, and 378 noninfected subjects. The persistent infection group included selleck chemical 166 males and 118 females suffering from biopsy-proven chronic hepatitis C (CHC) with compensated liver disease followed in the outpatient clinic of the Hospital Universitario Virgen del Rocío and Hospital Universitario de Valme (Sevilla, Spain) from 2001 to 2004. All CHC patients were hepatitis B surface antigen and human immune deficiency virus negative, anti-HCV positive, and HCV RNA positive in serum. Anti-HCV, HbsAg, and human immune deficiency virus were determined by commercially available methods (HCV 3.0 test, ORTHO, and Enzygnost hepatitis B surface antigen 5.0 and anti-human immune deficiency

virus-1/2 plus; DADE, Behring, respectively). PI3K inhibitor Percutaneous liver biopsies were performed under ultrasonographic control. A portion of the biopsy specimen was used for the histology diagnosis. Disease staging was defined according to Scheuer,8 with ranking from F0 (absence of fibrosis) to F4 (cirrhosis stage). Patients were stratified into two groups: F0-F2, absence of fibrosis to moderate fibrosis; and group F3-F4, with advanced fibrosis-cirrhosis. Data of response to treatment (51.4% received IFN-α, and 48.6% IFN-α 上海皓元医药股份有限公司 plus RVB) were available in 219 patients;

113 of them had a sustained response (SR), HCV RNA levels remained undetectable during 6 months after therapy discontinuation) and 106 had a nonsustained response (NSR), including nonresponder patients (HCV RNA levels detectable during the completed period of the treatment) and relapsed responder patients (undetectable HCV RNA during the therapy but detectable after discontinuation). The group with spontaneous viral clearance comprised 29 men and 40 women who were anti-HCV positive and HCV-RNA negative. Most of these subjects were blood donors with anti-HCV positive in the routine screening of viral antibodies; these subjects are referred to the hepatology unit and, according to the established protocol, HCV-RNA detection is performed. Lastly, a group of 223 male and 155 female blood and bone marrow donors (noninfected subjects [NIS]) were considered as representative of the “normal” frequencies of the SNP studied in the Spanish population. Patients and controls agreed to a blood examination according to the guidelines of the Hospital Bioethic Committee. DNA from patients and controls was extracted from peripheral blood using standard methods.