A new finding concerned the associations with IL28B rs12979860 genotype and GGT activity with treatment outcome. IL28B rs12979860 is a noncoding single nucleotide polymorphism Bioactive Compound Library datasheet (SNP) residing 3 kb upstream of the IL28B gene, which encodes IFN-λ3.15 GGT was strongly associated with the T allele, whose presence reduces the likelihood of response to therapy. While this finding confirms that

of another study,16 it must be noted that previous nonresponse to prior treatment could have biased the distribution of patients towards an overrepresentation of patients with TT genotype and high GGT. Of greater significance, patients with at least one copy of the T allele had poorer virological response with increasing GGT. In fact, patients homozygous for the T allele and in the highest quintile of GGT had a very low on treatment response rate (Fig. 2) and almost no chance of sustained virological response. In contrast, CC homozygotes had a favorable response rate that was relatively unaffected by GGT activity. It is not clear why GGT activity appears to potentiate the effect of the rs12979860 genotype. Among patients with chronic HCV, higher GGT activity has been associated with more severe liver disease in a number

of cross-sectional studies.17-23 GGT is also a component of two scores that were constructed for noninvasive evaluation of fibrosis stage.24, 25 However, cross-sectional studies provide check details inconclusive evidence that GGT is associated with liver disease progression. There are far fewer studies that have evaluated GGT in disease progression, and they were conducted among smaller or more heterogeneous patient populations than HALT-C.26, 27 A common problem with studies of disease progression is that few included GGT in the evaluation learn more of risk factors,

perhaps because it was not measured routinely. Therefore, it is significant that the current study demonstrated a statistically robust, increased rate of fibrosis progression and of clinical outcomes among patients with higher GGT. In particular, GGT activity was independent of previously established predictors, including histological features, for fibrosis progression and liver disease outcomes in the HALT-C cohort.28 GGT activity was also associated with increased risk of death and of liver transplantation. The association was not seen for HCC, perhaps because of different pathways to development of HCC than for other outcomes. However, other studies found an independent association of GGT activity and HCC in the general population and among patients with HCV.27, 29, 30 It is uncertain why GGT is associated with poorer prognosis with chronic hepatitis C, as well as greater severity of other liver diseases and with a number of diverse conditions, such as cardiovascular disease, type 2 diabetes, various malignancies, and overall mortality.2-4, 30-37 One likely reason is that GGT is a marker of oxidative stress, especially in its relationship to GSH metabolism.