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Pretreatment prediction of interferon-alfa efficacy in chronic hepatitis C patients.
Authors:Kazuhiro Hayashida  Akito Daiba  Akito Sakai  Takeshi Tanaka  Kyosuke Kaji  Niro Inaba  Satoshi Ando  Naoki Kajiyama  Hiroshi Terasaki  Aki Abe  Masanori Ogasawara  Michinori Kohara  Mine Harada  Takeshi Okanoue  Satoru Ito  Shuichi Kaneko
Affiliation:Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-ku, Fukuoka, Japan.
Abstract:BACKGROUND & AIMS: Interferon has been used widely to treat patients with chronic hepatitis C infections. Prediction of interferon efficacy before treatment has been performed mainly by using viral information, such as viral load and genotype. This information has allowed the successful prediction of sustained responders (SR) and non-SRs, which includes transient responders (TR) and nonresponders (NR). In the current study we examined whether liver messenger RNA expression profiles also can be used to predict interferon efficacy. METHODS: RNA was isolated from 69 liver biopsy samples from patients receiving interferon monotherapy and was analyzed on a complementary DNA microarray. Of these 69 samples, 31 were used to develop an algorithm for predicting interferon efficacy, and 38 were used to validate the precision of the algorithm. We also applied our methodology to the prediction of the efficacy of interferon/ribavirin combination therapy using an additional 56 biopsy samples. RESULTS: Our microarray analysis combined with the algorithm was 94% successful at predicting SR/TR and NR patients. A validation study confirmed that this algorithm can predict interferon efficacy with 95% accuracy and a P value of less than .00001. Similarly, we obtained a 93% prediction efficacy and a P value of less than .0001 for patients receiving combination therapy. CONCLUSIONS: By using only host data from the complementary DNA microarray we are able to successfully predict SR/TR and NR patients for interferon therapy. Therefore, this technique can help determine the appropriate treatment for hepatitis C patients.
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