[alpha]-Fetoprotein is a surrogate marker for predicting treatment failure in telaprevir-based triple combination therapy for genotype 1b chronic hepatitis C Japanese patients with the IL28B minor genotype

• Published in: Journal of medical virology Vol. 86; no. 3; pp. 461 - 472
• Main Authors: Shimada, Noritomo, Tsubota, Akihito, Atsukawa, Masanori, Abe, Hiroshi, Ika, Makiko, Kato, Keizo, Sato, Yoshiyuki, Kondo, Chisa, Sakamoto, Choitsu, Tanaka, Yasuhito, Aizawa, Yoshio
• Format: Journal Article
• Language: English
• Published: London Wiley Subscription Services, Inc 01.03.2014
• Subjects: Antiviral drugs; Drug therapy; Genotype & phenotype; Hepatitis; Hepatitis C virus; Proteins; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.23824

Even when treated with telaprevir-based triple therapy, some patients fail to achieve a sustained virological response. This study identified factors related closely to treatment failure. A total of 146 Japanese genotype 1b chronic hepatitis C patients were enrolled in this prospective, multicenter study and received a 24-week regimen of triple therapy. The end-of-treatment response rate was significantly lower in patients with the interleukin 28B (IL28B) (rs8099917) non-TT genotype (85.2%) than in those with the TT genotype (100%, P=0.0002). Multiple logistic regression analysis identified high [alpha]-fetoprotein levels as an independent factor related to non-end-of-treatment response in patients with the non-TT genotype. A cut-off value of 20ng/ml was determined for a non-end-of-treatment response; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 75.0%, 95.7%, 75.0%, 75.0%, and 92.6%, respectively. Multiple logistic regression analysis for a sustained virological response identified the IL28B TT genotype, low [alpha]-fetoprotein levels, non-responders, and a rapid virological response. The sustained virological response rate was significantly lower in patients with the non-TT genotype (59.3%) than in those with the TT genotype (96.7%, P<0.0001). In patients with the non-TT genotype, [alpha]-fetoprotein was the most significant predictor for non-sustained virological response by univariate analysis. A cut-off value of 7.4ng/ml [alpha]-fetoprotein was determined for non-sustained virological response; sensitivity, specificity, PPV, NPV, and accuracy were 63.6%, 87.5%, 77.8%, 77.8%, and 77.8%, respectively. For the non-TT patients, serum [alpha]-fetoprotein levels may be a surrogate marker for predicting treatment failure in telaprevir-based therapy for genotype 1b chronic hepatitis C. J. Med. Virol. 86:461-472, 2014. © 2013 Wiley Periodicals, Inc. [PUBLICATION ABSTRACT]