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Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study
Authors:Noritomo Shimada  Hidenori Toyoda  Akihito Tsubota  Tatsuya Ide  Koichi Takaguchi  Keizo Kato  Masaki Kondoh  Kazuhiro Matsuyama  Takashi Kumada  Michio Sata
Institution:1. Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, 1-380 Shinmatsudo, Matsudo, Chiba, 270-0034, Japan
2. Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
3. Institute of Clinical Medicine and Research, Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan
4. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan
5. Department of Hepatology, Kagawa Prefectural Central Hospital, 5-4-16 Bancho, Takamatsu, Kagawa, 760-8557, Japan
6. Department of Life Cycle Management, Roche Diagnostics K.K, 2-6-1 Shiba, Minato-ku, Tokyo, 105-0014, Japan
Abstract:

Background

Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a rapid virological response (RVR) have been reported as predictors for a sustained virological response (SVR) to telaprevir (TVR)-based triple combination therapy. However, the association between SVR and viral kinetics earlier than week 4 after initiation of therapy remains unclear. Thus, we evaluated the SVR prediction ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic hepatitis C (CHC) patients.

Methods

A total of 156 Japanese CHC patients received a 24-week regimen of TVR-based therapy. Baseline factors and reduction in HCV RNA levels at weeks 1 and 4 after the initiation of therapy were analyzed for SVR prediction.

Results

Multiple logistic regression analysis for SVR in TVR-based therapy identified the IL28B TT genotype, a reduction of ≥4.7 log10IU/mL in HCV RNA levels at week 1, RVR, and treatment-naïve/relapse. Whereas the SVR rate was higher than 90 % regardless of the reduction in HCV RNA levels at week 1 in patients with the TT genotype, a reduction of ≥4.7 log10IU/mL in HCV RNA levels at week 1 was the strongest predictor of SVR in patients with the non-TT genotype, as determined by multiple logistic regression analysis (P = 0.0043).

Conclusions

The IL28B TT genotype is the most important baseline factor for predicting SVR, and a ≥4.7 log10IU/mL reduction in HCV RNA at week 1 is a useful very early on-treatment predictor of SVR, especially in the non-TT genotype.
Keywords:
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