ABSTRACT FINAL ID: 1941
TITLE: Efficacy and safety of sofosbuvir-based therapies for cirrhotic and/or elder patients with hepatitis C virus in Japan
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Background and Aim: In Japan, sofosbuvir (SOF)-based therapies were approved for patients with hepatitis C virus (HCV) in May 2015. Now, elderly patients and those with advanced hepatic fibrosis, including those who have undergone curative treatment for liver cancer, are given interferon (IFN)-free therapy. We assessed the efficacy and tolerance of SOF-based therapies in Japan. Methods: The study enrolled 242 consecutive patients with HCV genotype 1 (G-1) beginning SOF/ledipasvir therapy, and 144 patients with HCV genotype 2 (G-2) beginning SOF/body-weight-adjusted ribavirin therapy. Resistance-associated variants (RAVs) were examined using direct sequencing. The G-1 cohort comprised 46 patients with compensated cirrhosis (108 males and 134 females; median age, 68 years; 16 patients >80 years old; baseline HCV viral load, 3.0-7.2 log copies/mL). 4 patients had a history of asunaprevir/daclatasvir treatment and 26 had failed treatment with an NS3/4 protease inhibitor plus Peg-IFN/ribavirin. 30 patients underwent curative treatment for HCC. The patients were treated with 400 mg of SOF and 90 mg of ledipasvir once daily for 12 weeks. The G-2 cohort comprised 16 patients with compensated cirrhosis (82 males and 62 females; median age, 64 years; 8 patients >80 years old; baseline HCV viral load, 2.1-7.3 log copies/mL). 7 patients underwent curative treatment for hepatocellular carcinoma (HCC) and 37 patients had failed IFN-based therapy. Clinical, biological, and virological data, including adverse effects, were recorded at baseline and during follow-up. Results: In G-1, 44 (18%) patients had RAVs in NS5A: L31M/F/I, Y93H, and both RAVs were detected in 13, 27, and 4 patients, respectively. RVR rate (HCV-RNA < 25 IU/mL at week 4) was 83% (172/206). HCV-RNA was under the detection level at the end of treatment in all 170 patients. No patient had developed HCV relapse after treatment as of 31 May 2016. Grade 3/4 AEs occurred in 11 patients. In G-2, RVR rate was 90% (112/124). At end of treatment, HCV-RNA was under the detection level in all 126 patients. The SVR4 and SVR12 rates were 99% (100/101) and 99% (85/86), respectively. One relapsed patient had hepatic cirrhosis; no S282 RAV was detected either pre- or post-treatment in this patient. No patients died during or after the SOF-based therapies. Grade 3/4 AEs were not associated with age, cirrhosis, and renal function. After the treatment, HCC recurred in three patients with G-1 and one patient with G-2. Conclusion: SOF-based therapies have high anti-viral effects and tolerability in the real world. It is still necessary to monitor the development of HCC after therapy.