EVLP as a treatment platform for Hepatitis C: could it radically expand donor lung availability?

Significant numbers of organ donors are Hepatitis C (HCV) positive. This may be as high as 20% in the current epidemic of overdose-deaths in the donor population⁽⁴⁾.

Successful use of organs from HCV-positive donors, with anti-viral treatment in the recipient, has been recorded, including for the lung⁽⁵⁾. But such treatment is expensive and lengthy. Any new and reliable means of inactivating the HCV viral load has the potential to significantly increase the availability of donor lungs.

Recently the Toronto group reported in Nature Communications⁽⁶⁾ their experience with anti-viral UVC light irradiation combined with ex-vivo lung perfusion (EVLP) in rejected, HCV-infected human and pig lungs. Previous work from the same group had shown EVLP alone to reduce the viral load in the Steen solution perfusate by up to 80%. But this was not sufficient to prevent recipient infection. Analogous reductions in bacterial load probably related to high antibiotic dosage in the perfusate, have previously been reported⁽⁷⁾.

Following integration of UV irradiation, however, into the EVLP circuitry in the Toronto Group´s 2019 study, perfusate viral load was reduced to zero after nine hours of EVLP. Pairs of HCV lungs were perfused: one lung from each pair was UV-irradiated whilst the other acted as control; i.e. both control and treated lungs came from the same donor and therefore had the same baseline viral load. Being a closed system, the same Steen solution perfusate passes through the UV tube several times during EVLP, resulting in a cumulative antiviral effect. As the authors point out, clearance or inactivation of the virus within the isolated organ prior to transplantation, not only increases the societal acceptance of using these organs but also avoids costs, toxicity and drug interactions related to systemic antiviral medication.

If this new approach, possibly with some supplementary anti-viral medication, is now shown clinically to reliably eliminate HCV, the authors predict that 1,000 new lung donors may well become available every year in North America alone!

This is a prime example of the potential for intervention during EVLP to restore previously unusable organs into the donor lung pool, with benefit of both more organs and simpler management in the recipient.

References:

4. Durand, C. M. et al. The drug overdose epidemic and deceased-donor transplantation in the united states: a national registry study. Ann. Internal Med. 168, 702–711 (2018) (link to abstract)
5. Khan, B. et al. Successful lung transplantation from hepatitis c positive donor to seronegative recipient. Am. J. Transplant. 17, 1129–1131 (2017) (link to abstract)
6. Galasso M, et al, Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion. Nat Commun. 2019 Jan 29;10(1):481. doi: 10.1038/s41467-018-08261-z (link to abstract)
7. Andreasson A, Karamanou D, Perry J et al, The effect of ex vivo lung perfusion on microbial load in human donor lungs. J Heart Lung Transplant 2014;33:910–916 (link to abstract)

Xvivo Insights PB-2019-03-26