Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in both groups (Fig. 4). Fig. 4 Virologic response by inosine triphosphatase genotype. RVR, Rapid virologic response; EVR, Early virologic response; SVR, Sustained virologic selleckbio response. To determine whether ITPA variant affects virological response, logistic regression analysis was used. A total of 125 patients who completed the anti-viral treatment were analyzed. Initially 10 factors, that is, gender, age (<60 yr), BMI>23 kg/m2, liver cirrhosis, genotype 1, RVR, EVR, RBV dose reduction (<20%), CC genotype of ITPA variant, and the recently reported IL28B variant (rs8099917, TT), were examined individually by univariate analysis.

Stepwise forward multiple logistic regression analysis was performed to identify independent factors. ITPA variant (rs1127354) showed no significant association (P=0.907). However, age, EVR, and IL28B (rs8099917, TT) remained significant by multivariate analysis (Table 3). Table 3 Univariate and multivariate analyses of host and viral factors associated with sustained virologic response DISCUSSION Most HCV infections progress to chronic disease and if left untreated and can lead to liver cirrhosis and hepatocellular carcinoma (12, 27). Interferon-alfa monotherapy was first used to treat CHC patients, but the SVR rate achieved was only 15 to 20%. Because of this serious shortcoming, combination therapy with anti-viral or anti-inflammatory drugs was examined.

It was found that a combination of PEG-IFN and RBV was most effective, and that it achieved SVR in more than 50% of patients (7). Currently, the standard anti-viral treatment Cilengitide for CHC is a combination of PEG-IFN and RBV (13). RBV (1-b-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) is a synthetic nucleoside analogue. Although RBV monotherapy has little antiviral activity against HCV, it improves treatment response and when used in combination with IFN increases the SVR rate to over 56% (14, 15). However, RBV often causes reversible hemolytic anemia, which often makes treatment intolerable (16). The standard dose of RBV used is 1,000-1,200 mg/day, and at this level over 50% of patients experienced a decline in Hgb level (17). Anemia begins early after treatment initiation, and is most serious after 4 weeks of treatment. Associated symptoms, such as, fatigue, decreased quality of life, can also occur. Furthermore, anemia often necessitates treatment withdrawal or RBV dose reduction (18). In addition, some have reported that lowering the RBV dosage may reduce the chance of SVR and increase the rate of relapse (17, 19).