Search

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty-six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25-35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment-naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25-35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25-35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1. [ABSTRACT FROM AUTHOR]

Pegylated interferon ( Peg- IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus ( HCV) infection and normal alanine aminotransferase levels ( NALT). However, it remains unclear whether the risk of hepatocellular carcinoma ( HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT ( ALT ≤ 40 IU/mL) treated with Peg- IFN alpha-2b and ribavirin for a mean observation period of 36.2 ± 16.5 months. The risk factors for HCC incidence were analysed by Kaplan- Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response ( SVR) or relapse compared with those showing nonresponse ( NR) ( SVR vs NR, hazard ratio ( HR): 0.16, P = 0.009, relapse vs NR, HR: 0.11, P = 0.037). Other risk factors were older age (≥65 years vs <60 years, HR: 6.0, P = 0.032, 60-64 vs <60 years, HR: 3.2, P = 0.212) and male gender (HR: 3.9, P = 0.031). Among 176 patients with PNALT ( ALT ≤ 30 IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT ( ALT ≤ 30 IU/mL) patients should be carefully determined. [ABSTRACT FROM AUTHOR]

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis ( P = 0.002), the timing of HCV RNA negativiation ( P < 0.001) and the mean doses of ribavirin ( P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given ≥12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 μg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (≥12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a body weight base from doses actually taken. From multivariate analysis, the mean dose of Peg-IFN α-2b during the first 12 weeks was the independent factor for c-EVR ( P = 0.02), not ribavirin. The c-EVR rate was 55% in patients receiving ≥1.2 μg/kg/week of Peg-IFN, and declined to 38% at 0.9–1.2 μg/kg/week, and 22% in patients given <0.9 μg/kg/week ( P < 0.0001). Even with stratified analysis according to ribavirin dose, the dose-dependent effect of Peg-IFN on c-EVR was observed, and similar c-EVR rates were obtained if the dose categories of Peg-IFN were the same. Furthermore, the mean dose of Peg-IFN during the first 12 weeks affected HCV RNA negativity at week 24 ( P < 0.0001) and SVR ( P < 0.0001) in a dose-dependent manner. Our results suggest that Peg-IFN was dose-dependently correlated with c-EVR, independently of ribavirin dose. Thus, maintaining the Peg-IFN dose as high as possible during the first 12 weeks can yield HCV RNA negativity and higher c-EVR rates, leading to better SVR rates in patients with CH-C genotype 1. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori)-related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults., Materials and Methods: This cross-sectional study included 14,716 subjects aged 20 years or more who underwent a health checkup between May 1997 and March 2013 in seven geographic areas throughout Japan. Relevant information on the demographics and status of H. pylori infection was retrieved from the electronic database. The univariate log-binominal regression model was used to estimate the prevalence of H. pylori infection, taking birth year into consideration. The multivariate log-binominal regression model was used to compare the prevalence of H. pylori infection between seven geographic areas., Results: The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Among seven geographic areas, Hokkaido showed the lowest prevalence (29.4%), while Yamagata Prefecture represented the highest (54.5%). The prevalence of H. pylori infection was highest in the 1940-1949 birth cohort and then decreased in the ensuing birth cohorts; the risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.84-0.87) for changes in the 10-year birth cohort. Individuals in Yamagata Prefecture had the highest RR of acquiring H. pylori infection in all three birth cohorts (RR = 1.53 for 1940, RR = 1.69 for 1950, and RR = 1.85 for 1960) when compared with those in Hokkaido., Conclusions: The prevalence of H. pylori infection increases with age and exhibits geographic variation in Japan. There has been a striking decrease in the prevalence of H. pylori infection, especially in younger Japanese populations., (© 2014 John Wiley & Sons Ltd.)