Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

BACKGROUND: National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1 year following lung transplantation from HCV-viremic versus uninfected donors. METHODS: We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. RESULTS: We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12 weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12 weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1 year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. CONCLUSIONS: We demonstrate the feasibility and success of using HCV NAT + donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

Difference in immunosuppressant dose requirement when transitioning to isavuconazole from other azoles in thoracic transplant recipients.

The triazole antifungal isavuconazole (ISAVU) is used for prevention and treatment of fungal infections in solid organ transplant (SOT). SOT recipients commonly need to transition from one azole to another due to breakthrough infection, toxicity, or other reasons. The purpose of our study was to evaluate the effect of ISAVU on immunosuppressant concentrations in thoracic transplant recipients when ISAVU was started de novo or transitioned from another azole. We conducted a single-center retrospective cohort study including 68 patients (51 lung, 14 heart, and 3 heart/lung transplant). Concentration to dosage ratios (C/D) of immunosuppressants were assessed at baseline, day 3, and weekly for 9 weeks. When starting ISAVU de novo, we observed a temporary doubling of tacrolimus exposure. Cyclosporine and sirolimus required dose decreases. Tacrolimus C/D increased by 110% at day 3 in patients started on ISAVU de novo then returned to baseline C/D ± 17% weeks 2-9 (n = 8). One cyclosporine patient started on ISAVU de novo had variable C/D, and C/D increased by 219% ± 72% in 2 sirolimus patients. When transitioning from other azoles, tacrolimus and cyclosporine required about twice the initial dose. After week 1, tacrolimus C/D decreased by 53% ± 6% in patients transitioned from posaconazole (n = 33), voriconazole (n = 14), or fluconazole (n = 2). Cyclosporine C/D decreased by 45% ± 16% in patients transitioning from other azoles (posaconazole [n = 2], voriconazole [n = 2], fluconazole [n = 1]). Sirolimus C/D decreased by 73% ± 13% in patients transitioned from posaconazole (n = 7). Aside from the initial loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in adjustments for the 4-week period after initiating antifungal therapy with ISAVU or switching from another agent.

A Pilot Trial for Prevention of Hepatitis C Virus Transmission From Donor to Organ Transplant Recipient With Short-Course Glecaprevir/Pibrentasvir.

A 7-day course of glecaprevir/pibrentasvir started in the preoperative period prevented transmission of hepatitis C virus (HCV) from viremic donors to 10 HCV-negative recipients (2 heart, 1 lung, 6 kidney, 1 heart/kidney) with 100% sustained virological response at 12 weeks.

Low dose posaconazole delayed release tablets for fungal prophylaxis in lung transplant recipients.

In November 2013, posaconazole delayed release (DR) tablets were approved by the FDA with the labeled dose of 300 mg daily for fungal prophylaxis. There are no studies demonstrating the appropriate dose in lung transplant recipients (LTR). We performed a 2-center retrospective cohort study of LTR taking posaconazole DR tablets for prophylaxis between January 2014 and January 2017. Mean serum trough concentrations and percentage of measurements ≥0.7 mcg/mL were compared by daily dose. Forty-nine subjects with 156 steady state serum posaconazole concentrations were included. There was a significant difference in percentage of first measured concentration ≥0.7 mcg/mL by initial daily dose (P = .04). The mean serum posaconazole concentration by dose was 0.9 (±0.42) mcg/mL for 100 mg daily, 1.66 (±0.91) mcg/mL for 200 mg daily, 2.39 (±1.49) mcg/mL for 300 mg daily, and 1.75 (±0.21) mcg/mL for 400 mg daily (P < .001). Mean concentrations were at goal in 63.3%, 96.9%, 94.9%, and 100% of subjects taking 100 mg, 200 mg, 300 mg, and 400 mg daily respectively (P = .04). Our results suggest that doses less than 300 mg daily of posaconazole DR tablets may be adequate to achieve target serum concentrations in LTR. Larger studies are needed to confirm these findings.