The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients

Abstract

SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA⁺ donors and none have reported quality of life (QOL).

Methods: This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA⁺ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center.

Results: Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA⁺ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA⁺ lung recipients versus matched comparators.

Conclusions: SHELTER adds important evidence regarding the safety of transplanting HCV-RNA⁺ lungs into uninfected recipients and suggests QOL benefits.

Graphical abstract

FIGURE 1.

Flowchart. HCV, hepatitis C virus.

FIGURE 2.

Recipient HCV viral load over time among 10 recipients of lung transplants from HCV-RNA⁺ donors. HCV, hepatitis C virus.

FIGURE 3.

Physical and mental health QOL scores from pretransplant (N = 9)* and at 12 mo posttransplant using HCV-RNA⁺ donor lungs (N = 10), assessed with the RAND-36 instrument. *One participant was too ill to complete pretransplant survey. HCV, hepatitis C virus; MCS, Mental Component Score; PCS, Physical Component Score; QOL, quality of life.

FIGURE 4.

ALT (A) and AST (B) over time among 10 recipients of lung transplants from HCV-RNA⁺ donors versus matched comparator recipients of HCV-negative donor lungs. Ten SHELTER lung transplants were matched to 30 HCV-negative lung transplants. ALT and AST levels of >250 IU/L were replaced with 250 IU/L to facilitate data presentation. Solid lines represent SHELTER trial participants; dashed lines represent matched comparator recipients of HCV-negative lungs. ALT, alanine transaminase; AST, aspartate transaminase; HCV, hepatitis C virus.

FIGURE 5.

PFTs among 10 recipients of lung transplants from HCV-RNA⁺ donors versus comparator recipients of HCV-negative donor lung transplants. FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; HCV, hepatitis C virus; PFT, pulmonary function test.