Pretreatment prediction of interferon-alfa efficacy in chronic hepatitis C patients.
OBJECTIVE
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.
Hayashida
Kazuhiro
K
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Higashi-ku, Fukuoka, Japan.
Daiba
Akito
A
Sakai
Akito
A
Tanaka
Takeshi
T
Kaji
Kyosuke
K
Inaba
Niro
N
Ando
Satoshi
S
Kajiyama
Naoki
N
Terasaki
Hiroshi
H
Abe
Aki
A
Ogasawara
Masanori
M
Kohara
Michinori
M
Harada
Mine
M
Okanoue
Takeshi
T
Ito
Satoru
S
Kaneko
Shuichi
S
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha