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Volume: 22 Issue: 4 April 2024

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CASE REPORT
Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient’s condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in liver transplant recipients.


Key words : Fungal infections, Immunocompromised, Opportunistic mycoses

Introduction

Fungal infections after liver transplant are becoming increasingly common, with reported incidence between 6% and 38%.1 Among these infections, mucormycosis accounts for approximately 2% to 4% of cases.1-3 Mucormycosis is a type of opportunistic mycosis caused by filamentous fungi of the Mucorales group. These fungi are characterized by broad, thin-walled hyphae that are sparsely septate and resemble ribbons.1 Mucormycosis primarily affects immunocompromised patients and poses a significant clinical challenge.

Case Report

We present the case of a 57-year-old man with a history of secondary biliary cirrhosis resulting from inadvertent bile duct injury during cholecystectomy and treated with a Y-en-Roux hepaticojejunostomy 1 week later. Subsequently, he experienced multiple episodes of cholangitis necessitating prolonged hospitalizations, percutaneous procedures, and transhepatic biliary drainages. The patient was then referred to our center where he underwent liver transplant. The liver graft was obtained from a 17-year-old male donor who had brain death as a result of trauma. The cold ischemia time was 10 hours, warm ischemia time was 39 minutes, and 6 units of packed red blood cells were transfused during the surgery. Basiliximab and steroids were used for induction.

Twelve hours after liver transplant, the patient underwent exploratory laparotomy and abdominal packing due to severe coagulopathy, requiring multiple transfusions. The patient subsequently exhibited recovery with satisfactory liver function and improving liver test results. However, on postoperative day 8, the patient developed fever. A computed tomography scan revealed a substantial area of hypoperfusion with gas bubbles in the liver dome (Figure 1). The finding was followed by a percutaneous biopsy, and preliminary results from a potassium hydroxide wet mount indicated the presence of a filamentous fungus, a diagnosis later confirmed through Grocott’s methenamine silver stain.

Liposomal amphotericin B was initiated because of high suspicion of mucormycosis. The patient remained afebrile and asymptomatic during the initial treatment period. However, after 5 days of antifungal therapy, follow-up imaging revealed the progressive nature of the lesion (Figure 2A). Consequently, the decision was made to proceed with surgical debridement. The patient was submitted to a surgical debridement, revealing the extensive involvement of the liver dome and diaphragm (Figure 2, B and C). A nonanatomic hepatectomy was performed (Figure 3). Despite surgery and intensive supportive measures, the patient’s condition worsened, requiring escalating doses of vasopressors. Tragically, the patient succumbed to multiple organ failure. Histopathological examination, including hematoxylin and eosin staining and periodic acid-Schiff staining of the resected liver, confirmed the diagnosis of mucormycosis caused by Rhizopus species (Figure 4). In addition, the culture was positive for Rhizopus species and Candida parapsilosis.

Discussion

Mucormycosis, a mycosis caused by fungi in the order of Mucorales of the class Zygomycetes, predo-minantly affects immunocompromised patients. Among the identified subgroups, Rhizopus, Mucor, and Lichtheimia species stand as the primary agents responsible for mucormycosis.4-6 These saprotrophic fungi, commonly found in soil and decaying matter, enter the human body through inhalation of spores, ingestion of contaminated food, or direct inoculation into disrupted skin or wounds.4,6

Establishing a definitive diagnosis of mucormy-cosis presents a considerable challenge, necessitating direct identification of the causative organism from specimens procured at the infection site. A number of laboratory techniques are employed for this purpose, including direct examination, such as wet mount and calcofluor staining, histological examination techniques involving Periodic acid-Schiff and Grocott’s methenamine silver stains, immunohistochemistry analysis comprising culture and antigen detection, and molecular approaches, such as direct sequencing, fluorescent in situ hybridization, and quantitative polymerase chain reaction.4,7

Mucormycosis rarely affects liver allografts, but few cases have been reported.3 In a review that included 116 cases of mucormycosis in solid-organ transplant recipients, 87% of patients had localized infections, whereas 13% had disseminated infections.8 The most commonly affected sites were rhino-sino-orbital (31%), pulmonary (24.1%), cutaneous (15.5%), gastrointestinal (11.2%), and renal allografts (5.2%).8 Several risk factors have been identified, including diabetes mellitus, cholestasis, hypertransfusion, acute rejection, high-dose steroids or use of OKT3, renal failure, bacterial infection, retransplant, malnutrition, and Candida species and cytomegalovirus infections.9 Transmission can occur through inhalation, ingestion, and percutaneous introduction of spores.10 Treatment typically involves liposomal amphotericin B and complete excision of the affected area, although we found a report of successful treatment with amphotericin B alone.2,9

Despite efforts, our patient’s clinical condition deteriorated after surgery, highlighting the high mortality rate in liver transplant recipients, ranging from 50% to 100%.2 The kidney allografts from the donor had been transplanted at another hospital and presented no issues, raising the possibility that the infection may have been acquired at our center. This theory is further supported by the patient’s specific risk factors, including cholestasis, hypertransfusion, and Candida infection. Alternatively, it is plausible that the organism was previously acquired during the numerous percutaneous procedures and biliary drainages, becoming active subsequent to the immunosuppressive regimen initiated by induction therapy (basiliximab and steroids) and sustained by maintenance immunosuppression (tacrolimus, cyclosporine, and steroids).

This case presents a rare instance of mucormy-cosis localized in the liver graft, which progressed despite medical and surgical treatment. Although surgical debridement is generally recommended for such infections, we question what might have occurred if we had pursued solely medical treatment, considering the patient’s clinical stability before surgery. The lesion was advancing on computed tomography scans, raising the possibility that surgery may have unintentionally exacerbated an already expected fatal outcome.


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Volume : 22
Issue : 4
Pages : 314 - 317
DOI : 10.6002/ect.2023.0142


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From the 1Ajmera Transplant Centre, University Health Network, Toronto General Hospital, Ontario, Canada; and the 2Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,” Mexico City, Mexico
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Mario Vilatobá, Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Avenida Vasco de Quiroga No. 15, Colonia Belisario Domínguez Sección XVI, Delegación Tlalpan, CP 14080, Ciudad de México, Mexico
E-mail: mvilatoba@hotmail.com