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Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1
Authors:Tsugiko Oze  Naoki Hiramatsu  Takayuki Yakushijin  Masanori Miyazaki  Sadaharu Iio  Masahide Oshita  Hideki Hagiwara  Eiji Mita  Yoshiaki Inui  Taizo Hijioka  Masami Inada  Shinji Tamura  Harumasa Yoshihara  Atsuo Inoue  Yasuharu Imai  Takuya Miyagi  Yuichi Yoshida  Tomohide Tatsumi  Tatsuya Kanto  Akinori Kasahara  Norio Hayashi  Tetsuo Takehara
Institution:1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
2. Higashiosaka City Central Hospital, Higashiosaka, Japan
3. Osaka Police Hospital, Osaka, Japan
4. Kansai Rousai Hospital, Amagasaki, Japan
5. National Hospital Organization Osaka National Hospital, Osaka, Japan
6. Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan
7. National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan
8. Toyonaka Municipal Hospital, Toyonaka, Japan
9. Minoh City hospital, Minoh, Japan
10. Osaka Rousai Hospital, Sakai, Japan
11. Osaka General Medical Center, Osaka, Japan
12. Ikeda Municipal Hospital, Ikeda, Japan
13. Department of General Medicine, Osaka University Hospital, Suita, Japan
Abstract:

Background

HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.

Methods

Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.

Results

The sustained virologic response (SVR) rate was 53 % for all patients, 60 % for those with genotype TT, and 19 % for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4 % (2/56) with <1 log10 decrease, 13 % (7/56) with 1–2 log10 decrease, 51 % (44/87) with 2–3 log10 decrease, 64 % (56/87) with 3–4 log10 decrease, 88 % (72/82) with more than 4 log10 decrease but with detectable HCV RNA and 100 % (33/33) with undetectable HCV RNA (p < 0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p = 0.005) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p = 0.004) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with non-response.

Conclusions

The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.
Keywords:
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