A Clinical Trial Evaluating the Effects of Ultra-Violet C treatment (UVC) during Ex Vivo Lung Perfusion (EVLP) as a Method of Inactivating Hepatitis C Infection in Donor Lungs

Purpose In pre-clinical studies we have demonstrated the ability of light-based therapies - UVC and photodynamic therapy (PDT) during EVLP to inactivate HCV in donor lungs. In a step-wise application of this technology to clinical transplantation, we designed a clinical trial to evaluate to effects of UVC treatment using NAT+ HCV donor lungs followed by transplantation. Methods Twenty patients receiving NAT+ HCV lungs were included in the study. In the control group, lungs were subjected to 5-6h of EVLP whereas in UVC group, lungs were subjected perfusate irradiation with UVC (254 nm, 31mW/cm²) followed by transplantation. Results 11 patients received lungs subjected to EVLP alone, and 9 patients received lungs subjected to EVLP+UVC. Donor viral loads were similar between the 2 groups (3585000 IU/ml vs. 3480000 IU/mL, p=0.56). During EVLP, lung function was stable and similar between the 2 groups. 19/20 patients developed viremia. Perfusate and tissue levels of HCV by PCR during EVLP were not significantly affected by UVC treatment (Fig.1A), however, the UVC group showed a marked delay in developing viremia post-transplantation (Fig 1B). Median day 7 viral loads were 4390 vs. 168 IU/ml; p=0.27 in control vs. UVC group respectively. The proportion of patients with viral loads less than 3-log copies at day 7 was 2/11 (18%) in control vs. 5/8 (62.5%) in UVC group; p=0.07. Survival post lung transplantation is 100% in both groups with a mean follow up of 162 (14-385) days. Conclusion This is the first clinical trial evaluating a therapeutic intervention during EVLP. As in our pre-clinical studies, UVC does not alter virus quantities measured by PCR (virus fragments) during EVLP, however it does appear to confer impairment in virus infectivity. The combination of UVC therapy with an ultra-short course of direct anti-virus agents may provide the ability to prevent transmission altogether, allowing expansion of transplantation using HCV+ organs.