title: α-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.
abstract: 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 α-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 20 ng/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 α-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, α-fetoprotein was the most significant predictor for non-sustained virological response by univariate analysis. A cut-off value of 7.4 ng/ml α-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 α-fetoprotein levels may be a surrogate marker for predicting treatment failure in telaprevir-based therapy for genotype 1b chronic hepatitis C.
authors.affiliation: Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan.
authors.forename: Noritomo
authors.initials: N
authors.lastname: Shimada
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Masanori
authors.initials: M
authors.lastname: Atsukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.forename: Makiko
authors.initials: M
authors.lastname: Ika
authors.forename: Keizo
authors.initials: K
authors.lastname: Kato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Chisa
authors.initials: C
authors.lastname: Kondo
authors.forename: Choitsu
authors.initials: C
authors.lastname: Sakamoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination / Q000379:methods; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D017211:Treatment Failure; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D000509:alpha-Fetoproteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C486464:telaprevir
keywords: HCV; IL28B; telaprevir; α-fetoprotein