European Association for the Study of the Liver (EASL) 2015
EASL 2015. Late-breaking Poster 17. Novel Approach for the Prevention of Recurrent Hepatitis C in Liver Transplant Recipients: Preliminary Results from Ongoing Phase III Trial with Civacir®
N. Terrault et al.
CARE Faculty Perspective:
Using a system dynamic model, we quantified the HCV-infected population in Canada (2014-2035). 36 age/gender-defined cohorts were tracked to define HCV prevalence, complications and mortality. Baseline assumptions, transition probabilities and SVR rates were extracted from the literature, and the availability of novel treatments (Rx) was based on expert opinion (2016: all-oral Rx for G1-3; 2018: pan-genotypic all-oral Rx). In the ‘base case', only patients with ≥F2 fibrosis were treated and no increase in Rx uptake over current levels (3,600 patients/yr) was assumed. Additional strategies modelled a stepwise increase in Rx due to the availability of novel agents (2015: 7,200 patients/yr; 2016-17; 10,800; and 2018-35: 20,000) and different fibrosis restrictions (≥F0, ≥F1, ≥F2 and ≥F3). Finally, a ‘progressive strategy' with a gradual decrease in fibrosis threshold (≥F2 until 2018; ≥F1 until 2022; ≥F0 from 2022-35) was modelled. A sensitivity analysis examined the impact of Rx volume increases (1- to 6-fold increase in Rx rates) on outcomes. The primary endpoint was disease elimination (>95% reduction in HCV infections, decompensated cirrhosis, hepatocellular carcinoma [HCC] and liver-related deaths).
63 patients were enrolled across 23 centres, with the majority of patients being Caucasian males. The majority of patients were infected with genotype 1 disease. The median pre-transplant MELD in the control group was higher in the control group (19.5) than in the low dose treatment group (12), but was comparable to the MELD in the high dose treatment group (23), although the median Child-Pugh score was similar across all three groups. The majority of patients were on a sofosbuvir-based regimen prior to treatment, and most patients had received at least 12 weeks of treatment, with the median duration of treatment averaging around 63.5 days. None of the patients in the high dose treatment arm had detectable viral loads at the time of transplant, whereas in the control and low dose arms, 14% and 33%, respectively, had detectable viral loads. Recurrence post-transplant was seen in the 32%, 30%, and 5% of the control, low dose, and high dose groups, respectively. In those patients who had detectable viral loads at the time of transplant, 1 of 3 patients in the control group and 4 of 6 patients in the low dose treatment arm had recurrence. Civacir was well tolerated, with the most common side effects being fever, shoulder pain and nausea. The interim results from this study suggest that, in G1 patients undergoing liver transplant, Civacir 300mg/kg can potentially prevent HCV recurrence post-transplant, although the final data will be of interest.
- CARE Liver Disease Faculty