1). For example, 25.4% of patients in the lowest quintile of GGT had SVR, compared with only 6.9% in the highest quintile. In multivariate

analysis increased GGT activity remained strongly associated with poorer treatment response when controlling for other independent predictors of response. For example, at week 20 of therapy the odds ratio selleck kinase inhibitor for virological response per quintile increase in GGT activity was 0.63 (95% CI = 0.55-0.72, P < 0.0001) when controlling for cirrhosis, previous ribavirin use, AST/ALT, AST, albumin, platelet count, IL28B genotype rs12979860, HCV genotype 1, and log HCV RNA level of ≥6. Among the covariates associated with treatment response, only IL28B genotype rs12979860 demonstrated a statistically significant interaction with GGT activity at all timepoints (P < 0.05). Therefore, the combined effect of GGT and IL28B genotype rs12979860 with treatment outcome was further examined (Fig. 2). As expected, CC homozygote patients had high rates of virological response. However, in this group there was not a statistically significant association Galunisertib chemical structure of GGT activity with virological response. In contrast, CT heterozygote and TT homozygote patients had lower rates of virological response with increasing

quintile of GGT. At the extremes, SVR occurred among 30% (74 of 250) of CC homozygote patients and in just 1 of 56 TT homozygote patients in the highest quintile of GGT activity. Of the 999 patients who entered the randomized phase and had GGT measured, enzyme activity was associated with the same variables as the patients who entered the lead-in (data not shown). In univariate Cox regression

analyses, GGT quintile was associated with any clinical endpoint (hepatic decompensation, HCC, or death; P < 0.0001) as well as with death or liver transplantation (P = 0.0003) and with HCC (P = 0.027). The cumulative incidence for each clinical outcome after 7 years of observation is shown in Fig. 3. There were 518 patients in the randomized phase with GGT measured who were eligible to have a 2-point increase Ishak fibrosis score (baseline 上海皓元 score of <5 and at least one follow-up biopsy). Among these patients, GGT activity was associated with a 2-point increase in Ishak fibrosis score on paired biopsies (P < 0.0001) (Fig. 3). In multivariate Cox regression analyses, increasing GGT quintile was associated with increased risk of any clinical endpoint, death or transplantation, 2-point increase in Ishak fibrosis score (Table 3), and death alone (not shown) when controlling for features previously found to be associated with any endpoint (platelet count, AST/ALT, albumin, total bilirubin, and fibrosis stage) or with fibrosis progression (body mass index [BMI], platelet count, and hepatic steatosis). Association with HCC was not statistically significant (P = 0.46).