High rates of sustained virological response at 12 weeks in a real-world hospital-based cohort of direct-acting antiviral-treated patients with hepatitis C virus (HCV): The observational, prospective epidemiological registry in Australia of HCV (OPERA-C).

Abstract

Background and Aim: Publicly funded hepatitis C virus (HCV) treatment became available in Australia in March 2016. The Observational, Prospective Epidemiological Registry in Australia of HCV (OPERA-C) is an ongoing prospective study evaluating clinical and virological outcomes in patients with HCV receiving direct-acting antiviral (DAA) therapy across 29 Australian hospitals. Method(s): Clinical, epidemiological, virological, and treatment history data, including sustained virological response at 12 weeks (SVR12), are collected for patients with HCV at baseline and at 6-month intervals for 2 years. Linkage to Australian universal health care data will occur for prescriptions, cancer, and death. Clinical factors associated with SVR12 were assessed by univariate and multivariable logistic regression. Result(s): A total of 3144 patients (mean age, 52 years; range, 18-90 years; 66% male; 88% Caucasian, 3% Indigenous) were recruited by February 2019. Of these, 1694 (54%) had HCV genotype (Gt) 1 (Gt 1a, 39.6%; Gt 1b, 11.8%), 842 (27%) had Gt 3, and 148 had Gt 2. The median liver stiffness of the cohort was 7.4 kPa (IQR, 5.4-12.8). At enrolment, 961 (31%) had cirrhosis, of whom 65 (2%) had decompensated cirrhosis. The median duration of HCV infection in the cohort was 21 years (IQR, 15-30) and was longer in those with cirrhosis (26 years; P < 0.05). Overall, 79% of patients were treatment-naive. Of the patients with Gt 1, 75% received sofosbuvir plus ledipasvir, while 77% of those with Gt 3 received sofosbuvir plus daclatasvir. Sixteen percent of patients had received one prior treatment and 5% had two or more prior treatments. The overall rate of SVR12 was 97%. Per protocol SVR12 data are available for 1354 patients (Table 1). SVR varied by genotype (7.5% relapse in Gt 3 vs 4.3% in Gt 2 and 1.3% in Gt 1; P < 0.001) and by cirrhosis status (7.0% relapse with vs 2.2% without cirrhosis; P < 0.001), with the lowest SVR seen in (Table presented) those with Gt 3 cirrhosis (89%). There was no difference by compliance, treatment regimen, or opiate prescription. On multivariable analysis, Gt 3 (odds ratio [OR], 4.27; 95% CI, 2.24-8.14; P < 0.005), albumin (OR, 0.94; 95% CI, 0.88-0.99; P = 0.033), and cirrhosis (OR, 2.15; 95% CI, 1.00-4.63; P = 0.050) were independently associated with lower SVR. Eighty-five patients had hepatocellular carcinoma (HCC) at enrolment and 26 patients developed HCC after enrolment; three before or during HCV treatment and 20 developed HCC less than 100 days after treatment commencement (missing data for three patients). Conclusion(s): OPERA-C is the largest cohort of liver patients assembled in Australia to date and is enriched for advanced liver disease. Overall SVR12 rates were high, confirming the real-world efficacy of DAA treatment. Higher failure rates were seen in patients with cirrhosis and Gt 3 HCV infection. This cohort will be used to define long-term clinical outcomes after DAA treatment in Australian patients, including the impact of virological response on HCC risk and liver-related mortality.