Final challenges: real-world experience with sofosbuvir, velpatasvir and voxilaprevir in patients with advanced cirrhosis.

Background and Aims: In clinical trials, salvage therapy including Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of 96% in NS5A-experienced participants. An extended access program (EAP) for SOF/VEL/VOX was sponsored by Gilead Pharmaceuticals for Australian patients with advanced liver disease or prior liver transplantation (LT), who had relapsed. We determined the real-world efficacy and safety of this regimen in this cohort with advanced liver disease. Method(s): In this Australian multicentre EAP study, adult patients with chronic HCV infection genotype(GT)1-6 with prior failure on a DAA NS5A inhibitor containing regimen were eligible to access 12 weeks of SOF/VEL/VOX 400 mg/100 mg/100 mg. Other eligibility criteria included compensated liver disease with at least one of the following i) Child Pugh (CP)A cirrhosis with clinically significant portal hypertension or platelets <100 x 109/L, ii) prior LT, or iii) severe extra hepatic manifestations. Hospitals with >1 EAP recipient were invited to participate. Clinical characteristics and treatment outcomes were recorded at baseline, end-of-treatment (EOT) and SVR12. HCV NS5A RAS testing was performed prior to retreatment, where serum was available. The primary outcomes was SVR12 rate. Result(s): To date, baseline data is available for 89 patients from 24 participating hospitals. 85 have reached end-of-treatment (EOT), and 80 have SVR12 data available for analysis. Four patients have incomplete data due to early discontinuation of therapy (n = 2), loss to follow up (n = 1) and death (n = 1). 74 (83%) were male and the median age was 53. GT3 was the most common (n = 64), then GT1a (n = 18), GT1b (n = 4), GT6 (n = 2) and GT4 (n = 1). The median platelet count was 127. 68 (75%) had cirrhosis and of these, 35 (51%) had portal hypertension. 14 (16%) had prior hepatoma and 15 (17%) prior LT. All participants were NS5A-experienced and 8 (9%) had received?>1 DAA course (1-4). Three participants were