Norio Akuta1, Joji Toyota2, Yoshiyasu Karino2, Fusao Ikeda3, Akio Ido4, Katsuaki Tanaka5, Koichi Takaguchi6, Atsushi Naganuma7, Eiichi Tomita8, Kazuaki Chayama9, Shigetoshi Fujiyama10, Yukiko Inada11, Hitoshi Yoshiji12, Hideaki Watanabe13, Hiroki Ishikawa13, Fiona McPhee14, Stephanie Noviello15, Hiromitsu Kumada16. 1. Toranomon Hospital, Tokyo, Japan. norioakuta@toranomon.gr.jp. 2. Sapporo-Kosei General Hospital, Sapporo, Japan. 3. Okayama University, Okayama, Japan. 4. Kagoshima University, Kagoshima, Japan. 5. Yokohama City University Medical Center, Yokohama, Japan. 6. Kagawa Prefectural Central Hospital, Takamatsu, Japan. 7. Takasaki General Medical Center, Takasaki, Japan. 8. Gifu Municipal Hospital, Gifu, Japan. 9. Hiroshima University, Hiroshima, Japan. 10. Kumamoto Shinto General Hospital, Kumamoto, Japan. 11. Miyazaki Medical Center Hospital, Miyazaki, Japan. 12. Nara Medical University, Kashihara, Japan. 13. Bristol-Myers Squibb K.K., Tokyo, Japan. 14. Bristol-Myers Squibb, Wallingford, CT, USA. 15. Bristol-Myers Squibb, Princeton, NJ, USA. 16. Toranomon Hospital, Tokyo, Japan.
Abstract
BACKGROUND: In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3. METHODS: Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment. RESULTS: Of 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 107 IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP < 6 μg/L remained < 6 μg/L and 51% with baseline AFP ≥ 6 μg/L were < 6 μg/L post-treatment. CONCLUSIONS: DCV-TRIO administered for 12 weeks to Japanese patients with primarily GT-1b infection achieved a high SVR12 rate and resulted in improved measures of hepatic fibrosis and serum AFP that may reduce the risk of future liver disease progression and hepatocellular carcinoma, particularly in those with compensated cirrhosis.
BACKGROUND: In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3. METHODS: Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment. RESULTS: Of 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 107 IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP < 6 μg/L remained < 6 μg/L and 51% with baseline AFP ≥ 6 μg/L were < 6 μg/L post-treatment. CONCLUSIONS:DCV-TRIO administered for 12 weeks to Japanese patients with primarily GT-1b infection achieved a high SVR12 rate and resulted in improved measures of hepatic fibrosis and serum AFP that may reduce the risk of future liver disease progression and hepatocellular carcinoma, particularly in those with compensated cirrhosis.
Authors: Fred Poordad; William Sievert; Lindsay Mollison; Michael Bennett; Edmund Tse; Norbert Bräu; James Levin; Thomas Sepe; Samuel S Lee; Peter Angus; Brian Conway; Stanislas Pol; Nathalie Boyer; Jean-Pierre Bronowicki; Ira Jacobson; Andrew J Muir; K Rajender Reddy; Edward Tam; Grisell Ortiz-Lasanta; Victor de Lédinghen; Mark Sulkowski; Navdeep Boparai; Fiona McPhee; Eric Hughes; E Scott Swenson; Philip D Yin Journal: JAMA Date: 2015-05-05 Impact factor: 56.272
Authors: Fiona McPhee; Amy K Sheaffer; Jacques Friborg; Dennis Hernandez; Paul Falk; Guangzhi Zhai; Steven Levine; Susan Chaniewski; Fei Yu; Diana Barry; Chaoqun Chen; Min S Lee; Kathy Mosure; Li-Qiang Sun; Michael Sinz; Nicholas A Meanwell; Richard J Colonno; Jay Knipe; Paul Scola Journal: Antimicrob Agents Chemother Date: 2012-08-06 Impact factor: 5.191
Authors: Julie A Lemm; Mengping Liu; Robert G Gentles; Min Ding; Stacey Voss; Lenore A Pelosi; Ying-Kai Wang; Karen L Rigat; Kathleen W Mosure; John A Bender; Jay O Knipe; Richard Colonno; Nicholas A Meanwell; John F Kadow; Kenneth S Santone; Susan B Roberts; Min Gao Journal: Antimicrob Agents Chemother Date: 2014-04-14 Impact factor: 5.191