Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C

• Published in: Journal of gastroenterology Vol. 49; no. 12; pp. 1548 - 1556
• Main Authors: Fujino, Hatsue, Imamura, Michio, Nagaoki, Yuko, Kawakami, Yoshiiku, Abe, Hiromi, Hayes, C. Nelson, Kan, Hiromi, Fukuhara, Takayuki, Kobayashi, Tomoki, Masaki, Keiichi, Ono, Atsushi, Nakahara, Takashi, Honda, Youji, Naeshiro, Noriaki, Urabe, Ayako, Yokoyama, Satoe, Miyaki, Daisuke, Murakami, Eisuke, Kawaoka, Tomokazu, Hiraga, Nobuhiko, Tsuge, Masataka, Hiramatsu, Akira, Hyogo, Hideyuki, Aikata, Hiroshi, Takahashi, Shoichi, Miki, Daiki, Ochi, Hidenori, Ohishi, Waka, Chayama, Kazuaki
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.12.2014; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Age Factors; Aged; Aged patients; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Biliary Tract; Biological response modifiers; Care and treatment; Colorectal Surgery; Comparative analysis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastroenterology; Genetic aspects; Genotype; Hemoglobin; Hepacivirus - genetics; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Hepatology; Humans; Interferon; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Interleukins - genetics; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; Multivariate Analysis; Oligopeptides - administration & dosage; Oligopeptides - therapeutic use; Original Article—Liver; Pancreas; Patient outcomes; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - therapeutic use; Polymorphism, Single Nucleotide; Predictive Value of Tests; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Regression Analysis; Ribavirin; Ribavirin - administration & dosage; Ribavirin - therapeutic use; Surgical Oncology; Treatment Outcome; Young Adult; Older patients; Telaprevir; Hepatitis C virus; IFNL4; RVR
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-013-0924-9

Background Older patients with chronic hepatitis C have a lower virological response to interferon (IFN) treatment compared to younger patients. The efficacy of telaprevir (TVR) and PEG-IFN plus ribavirin combination therapy and the predictive value of recently identified IFN lambda (IFNL) 4 polymorphisms on the outcome of therapy for older patients have not been addressed. Methods We assessed predictive factors for sustained virological response (SVR) to triple therapy in 226 younger (≤65 years) and 87 older (>65 years) Japanese patients with chronic genotype 1 hepatitis C. IFNL4 polymorphism ss469415590 was analyzed by Invader assay. Results The SVR rate for older patients was slightly lower than for younger patients (69 vs. 82 %, P  = 0.043). In the older group, the SVR rate for patients with the IFNL4 TT/TT genotype was significantly higher than patients with TT/ΔG or ΔG/ΔG genotypes (81.8 and 42.9 %, P  = 0.003). In multivariate regression analysis, rapid virological response (OR 36.601, P  = 0.002) and IFNL4 TT/TT genotype (OR 19.502, P  = 0.009) were identified as significant independent predictors for SVR in older patients. Treatment-related decreases in hemoglobin and increases in serum creatinine were higher in older patients than younger patients. Reduction of initial TVR dose to 1,500 mg per day alleviated these adverse events without compromising SVR rate in older patients. Conclusions Analysis of IFNL4 polymorphisms is a valuable predictor in older patients receiving TVR triple therapy. 1,500 mg per day is a suitable initial TVR dose for older Japanese patients.