Liver Transplantation in Patients With Pretransplant Aspergillus Colonization: Is It Safe to Proceed?

Abstract

Background. Patients with end-stage liver disease and pretransplant Aspergillus colonization are problematic for determining liver transplant candidacy and timing of transplantation because of concerns for posttransplant invasive aspergillosis. Methods. We performed a retrospective review of the medical and laboratory records of all adult patients (aged ≥18 y) who underwent liver transplantation with pretransplant Aspergillus colonization at the Ronald Reagan University of California, Los Angeles, Medical Center from January 1, 2010, to December 31, 2015. Results. A total of 27 patients who had Aspergillus colonization (respiratory tract 26, biliary tract 1) before liver transplantation were identified. Pretransplant characteristics included previous liver transplant (11 of 27, 40.7%), dialysis (22 of 27, 81.5%), corticosteroid therapy (12 of 27, 44.4%), intensive care unit stay (27 of 27, 100%), and median model for end-stage liver disease score of 39. Only 22.2% (6 of 27) received pretransplant antifungal agents (median duration, 5 d), whereas 100% (27 of 27) received posttransplant antifungal prophylaxis (voriconazole 81.4%, 22 of 27; echinocandin 14.8%, 4 of 27; voriconazole plus echinocandin 3.7%, 1 of 27) for median duration of 85 d. Posttransplant invasive fungal infection occurred in 14.8% (4 of 27; aspergillosis 3, mucormycosis 1). Both 6-month and 12-month survival were 66.7% (18 of 27), but only 1 death was due to fungal infection. Other causes of death were liver graft failure, intraabdominal complications, and malignancy. Conclusions. A substantial number of patients with pretransplant Aspergillus colonization can still undergo successful liver transplantation if they are otherwise suitable candidates and receive appropriate antifungal prophylaxis. Posttransplant outcome in these patients is determined mostly by noninfectious complications and not fungal infection. Pretransplant Aspergillus colonization alone should not necessarily preclude or delay liver transplantation.

Fungal Infections in Liver Transplant Recipients

“…Recently, a retrospective evaluation of Aspergillus -colonized liver transplant recipients, all of whom received Aspergillus -directed antifungal prophylaxis, predominantly with voriconazole, found only one death due to fungal infection, but also noted decreased survival from baseline, and breakthrough infections were identified. The median duration of prophylaxis was also prolonged, 85 days vs. typical 8 weeks [ 108 ]. This suggests that transplantation can be sought with Aspergillus colonization but carries increased risk, and that any pretransplant colonization demands prophylaxis and expert management.…”

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta‐analysis

“…Overall, 1725 enrolled patients were included. Three RCTs 6,7,20 and seven observational studies (two prospective and five retrospective) were included 8,21–26 . Half of the studies were multicentric.…”

“…Three RCTs 6 , 7 , 20 and seven observational studies (two prospective and five retrospective) were included. 8 , 21 , 22 , 23 , 24 , 25 , 26 Half of the studies were multicentric. Among the 10 included studies, five were conducted in USA, four in Europe and one in Asia.…”

“…Micafungin, caspofungin and anidulafungin were investigated in five, four, and three studies, respectively (in two studies different echinocandins were allowed for prophylactic use 8,21 ). Comparators…”

Invasive fungal infection before and after liver transplantation

“…Broad-spectrum antibiotic therapy, parenteral nutrition, prolonged neutropenia, ICU stay, diabetes, pre-LT colonization, renal replacement therapy, cytomegalovirus (CMV) infection, re-interventions and choledochojejunostomy are established risk factors for post-LT IC[ 34 , 35 ], whereas pre-LT steroid administration, ALF, and renal replacement therapy seem to be more frequently associated with IA[ 36 - 38 ]. Recently, pre-LT Aspergillus colonization has been considered not a contraindication to LT in a single-center cohort of 27 patients; although they received appropriate post-operative prophylaxis (voriconazole +/- echinocandin), post-LT IA occurrence was 11%[ 39 ]. Most of the abovementioned risk factors are associated with patient’s severity at time of transplantation.…”