In our patient population, the frequency of the C allele of rs12979860 was
69%, slightly higher than that reported in Americans of North European descent9, 13 and similar to that reported in a Spanish cohort of HCV-infected patients.16 The distribution of rs12979860 and rs8099917 genotypes were similar to an ethnically-matched control population, indirectly implying an absence of effect on natural clearance of HCV genotype 3. This is in contrast to the effect found in HCV genotype 1–infected cohorts and may explain why the CC genotype of rs12979860 is found more frequently in HCV genotype 2/3–infected GSK2126458 cell line patients compared to HCV genotype 1–infected patients.13 Furthermore, absence of association of SVR with the CC genotype of rs12979860 and differential distribution of CC genotype in HCV genotype 3–infected patients compared to HCV genotype 1–infected patients do not explain why IFN-based therapies are more effective in HCV genotype 3–infected patients compared to HCV genotype 1. Studies of Mangia et al.15 and Thomas et al.24 show a possible role of IL28B in natural clearance of HCV genotype check details 2 from infected patients, implying that the lack of an apparent effect on natural clearance might be specific to HCV genotype 3. Mathematical modeling of PEG-IFN/ribavirin therapy has pointed to the biphasic and/or triphasic nature
of therapy with ribavirin exerting its mutagenic effect in preventing viral rebound after a rapid initial drop in HCV RNA in response to PEG-IFN. Yet rs12979860 seems to be associated with natural clearance of HCV genotype 1 virus, high baseline viral load prior to therapy (presumably in patients selleck screening library who have not achieved natural clearance), an early response to therapy, and finally two opposite courses in the final stages, sustained response in HCV genotype 1–infected patients and relapse in HCV genotype 3–infected patients. The opposing effects of polymorphisms near the IL28B gene warrant further investigation with regard to their effect on natural immune response
to HCV infection and to their effects on HCV after PEG-IFN/ribavirin therapy. However, it does limit the utility of using these polymorphisms as indicators for treatment in HCV-genotype 1–infected patients. In HCV genotype 3–infected patients, rs12979860 and rs8099917 major genotypes may identify patients who are likely to relapse after RVR for prolonged therapy or for adjunct therapy. We thank the Norwegian Bone Marrow Donor Registry and Dr. Benedicte A. for making the control material available. We also thank the KBC and North-C study groups, as well as Schering Plough for their financial support that covered administrative costs for the two investigator initiated studies. “
“Background and Aim: Percutaneous radiofrequency ablation (RFA) has been shown to be a highly effective treatment for hepatocellular carcinoma (HCC).