Risk factors for invasive aspergillosis in living donor liver transplant recipients

Abstract

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P ϭ 0.02) and preoperative steroid administration (P ϭ 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT. Liver Transpl 13:566-570, 2007 Living donor liver transplantation (LDLT) has been a predominant procedure in Asian countries. Increased indications and growing numbers of referrals for deceased donor liver transplantation (DDLT) have led to an increasing disparity between the number of patients waiting for transplantation and the number of donor organs, resulting in high mortality among candidates on the waiting list. Since the indications for LDLT were expanded from pediatric to adult liver diseases, such as hepatitis virus infections with or without hepatocellular carcinoma, LDLT has been accepted as a therapeutic alternative even in the United States and Europe. 1 Although small-for-size in LDLT leads to septic complications and higher mortality, 2 recent studies have shown comparable results in LDLT and DDLT for hepatitis C virus-positive patients. 3 Furthermore, the incidence of surgical site infections in LDLT was also similar to that reported in DDLT. 4 However, few studies have reported other infectious complications in LDLT.Aspergillus spp. is the second most common fungal pathogen responsible for infection of liver transplant recipients. The frequency of invasive aspergillosis (IA) among DDLT recipients ranges from 1 to 8%, 5 but the IA-related mortality rate for these patients exceeded 90% 6 and an estimated 16.9% of all deaths among DDLT recipients were due to Aspergillus infections.

Radiological and clinical findings of 25 patients with invasive pulmonary aspergillosis: retrospective analysis of 2150 liver transplantation cases

“…Ground-glass opacity surrounding the nodules, the halo sign, was common in our study (80%). Because the halo sign has also been reported in patients with IPA after HSCT and patients with other immunocompromised conditions, it is not a specific radiological finding of IPA after liver transplantation [9][10][11][12][13]. However, the halo sign is still a useful finding for early diagnosis of IPA and has been pathophysiologically characterised as a discrete nodule of angioinvasive aspergillosis with infarction and coagulative necrosis surrounded by alveolar haemorrhage [9].…”

“…The Aspergillus genus is one of the most common types of fungal disease in liver transplant patients. Although the radiological and clinical findings of invasive pulmonary aspergillosis (IPA) in patients with haematopoietic stem cell transplantation (HSCT), acquired immunodeficiency syndrome (AIDS), non-AIDS immunocompromised status and immunocompetent status have been studied, the radiological and clinical manifestations of IPA have rarely been reported in a large number of liver transplant patients [7][8][9][10]. Therefore, the purpose of our study was to assess the radiological and clinical findings of IPA in liver transplant recipients.…”

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“…Aspergillosis may occur in transplant recipients who have laparotomy after transplant, cytomegalovirus infection, prolonged hospitalization, or vascular complications and may occur concurrently with bacteremia. 2,10,11 Invasive aspergillosis in transplant recipients may present with pneumonia, disseminated disease, an intra-abdominal collection, meningitis, or a wound infection. Diagnosis of invasive aspergillosis may be difficult because the infected organ may be inaccessible, precluding histopathologic evaluation for tissue invasion.…”

Infections After Orthotopic Liver Transplantation

“…64 The identification of potential risk factors may reduce the morbidity and mortality rates of invasive aspergillosis are necessary but reports have been variable and conflicting in some instances with regards to the importance of immunosuppression. [64][65][66] Suspected risk factors for invasive aspergillosis including: renal insufficiency, the need for renal replacement therapy post-transplantation, retransplantation, CMV infection, repeated bacterial infections, preoperative ICU stay, preoperative steroid administration, fulminant hepatic failure, the presence of Aspergillus antigenemia, and the use of OKT3 monoclonal antibody. 65,67,68 Antifungal therapy should be instituted upon any clinical suspicion of aspergillosis without waiting for microbiology results.…”

“…[64][65][66] Suspected risk factors for invasive aspergillosis including: renal insufficiency, the need for renal replacement therapy post-transplantation, retransplantation, CMV infection, repeated bacterial infections, preoperative ICU stay, preoperative steroid administration, fulminant hepatic failure, the presence of Aspergillus antigenemia, and the use of OKT3 monoclonal antibody. 65,67,68 Antifungal therapy should be instituted upon any clinical suspicion of aspergillosis without waiting for microbiology results. For severely immunocompromised patients after liver transplantation, a heightened level of suspicion for invasive fungal infection development is needed as is a prompt and aggressive search for etiology.…”