Unlike the reports on Caucasian and African American patients, it may be that overall adherence to RBV is important in Japanese patients. It was notable that adherence to peg-IFN-2b significantly influenced SVR in this study. demonstrated to be the main factors associated with SVR. CONCLUSION: Peg-IFN-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients ENTPD1 with CHC and resulted in a SVR rate of 44.3%. Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFN-2b is usually important in improving Amodiaquine hydrochloride the SVR rate. Keywords:Chronic hepatitis C, Pegylated interferon, Ribavirin == INTRODUCTION == In Japan, annual mortality due to liver cancer exceeds 30 000 and 75% of liver cancer is associated with hepatitis C computer virus (HCV) contamination[1]. The combination of pegylated interferon (peg-IFN) plus ribavirin (RBV) is one of the most effective therapies for chronic hepatitis C (CHC), and the effect of this combination is reported to be higher than standard interferon[2,3]. However, the majority of Japanese CHC patients are infected with HCV genotype Ib and have a high viral weight, and treatment with standard interferon has its troubles[4]. CHC patients in Japan tend to be older than CHC patients in other countries therefore, problems such as a higher incidence of liver malignancy and lower tolerability to treatment have been observed[4,5]. The HCV strain and the efficacy of interferon treatment vary between races and countries[6,7]. Identification of the factors associated with treatment efficacy is extremely important, however, few studies involving large populations have reported on the treatment of Japanese CHC patients with pegylated interferon alpha-2b (peg-IFN-2b) plus RBV[8,9]. In this study, we evaluated the efficacy and security of peg-IFN-2b plus RBV therapy in CHC genotype Ib patients with a high viral load. This treatment became available in Japan for health insurance approved treatment from December 2004. In addition, we attempted to identify predictive factors for treatment end result. == MATERIALS AND METHODS == == Study population == One hundred and thirty CHC genotype Ib patients with a high viral weight, who received peg-IFN-2b plus RBV therapy in our hospital or our affiliated institutions between December 2005 and November 2006 were enrolled in this study. The diagnosis of CHC was based on the following criteria; HCV antibody positive, HCV-RNA positive and elevation of serum alanine aminotransferase (ALT) activity (> 35 IU/L) within 6 mo of screening. Exclusion criteria were leucopenia [white blood cell (WBC) count number < 3000/L], Amodiaquine hydrochloride neutropenia [neutrophil (ne) count number <1500/L], thrombocytopenia [platelet (PLT) count number < 90 000/L], anemia [hemoglobin (Hb) < 12 g/dL], cirrhosis, creatinine clearance < 50 mL/min, uncontrolled mental disorder, severe heart Amodiaquine hydrochloride or lung disease, or autoimmune disease. The study was approved by the ethical committee of Tohoku University or college according to the Declaration of Helsinki. All patients gave written informed consent before enrollment. == Treatment regimen == The patients received peg-IFN-2b (Pegintron; Schering-Plough, Kenilworth, NJ, USA) at a dosage of 1 1.5 mg/kg every week subcutaneously for 48 wk. Daily RBV (Rebetol, Schering-Plough) was given orally for 48 wk and the dosage was adjusted according to excess weight (600 mg for 60 kg, 800 mg for 60 to 80 kg, 1000 mg for > 80 kg). Blood samples were obtained every four weeks and were analyzed for biochemical parameters including ALT and HCV RNA levels. The HCV genotype was decided using a kit. HCV genotype was determined by PCR using a mixed primer set derived from the nucleotide sequences of the NS5 region. HCV RNA levels were measured by quantitative RT-PCR (Amplicor, Roche Diagnostic Systems, CA, USA). HCV RNA negativity was evaluated by qualitative RT-PCR (Amplicor, Roche), which has a higher sensitivity than the quantitative method. The lower limit of the assay in the quantitative method was 5 KIU/mL (equivalent to 5000 copies/mL) and was 50 IU/mL (equivalent to 50 Amodiaquine hydrochloride copies/mL) in the qualitative method. Early virological response (EVR) was defined as undetectable HCV RNA after 12 wk. Sustained virological response (SVR) was defined as undetectable HCV RNA at 24 wk after completion of treatment. == Statistical analysis == Fishers exact test and the Mann-WhitneyUtest were used to evaluate the parameters [age, sex, excess weight, body mass index (BMI), EVR, peg-IFN adherence, RBV adherence, HCV RNA, ALT, WBC, Hb, and PLT] to determine SVR. Quantitative data were divided into two groups using the median to examine the differences. We conducted multivariate analysis using binary logistic regression around the parameters which achieved statistical significance (P< 0.05) using univariate analysis. All analyses were performed using a statistical software package (StatView-J version 5.0, SAS Institute Inc..