الفهرس 
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Abstract
SUMMARY
Invasive fungal infections have been reported in 5% to 42% of
liver transplant recipients with an associated mortality rate of 25% to
71%. Risk factors of fungal infection relate to transplantation factors, and
donor and recipient factors. Transplant factors include ischemiareperfusion
damage, amount of intra-operative blood transfusion, level
and type of immunosuppression, rejection, and complications, prolonged
intensive care stay with dialysis or ventilation, antibiotics, antiviral
regimen, and environment. Donor risk factors include infection,
prolonged intensive care, and viral status. For the recipient, the most
important are: model of end stage liver disease (MELD) score >30,
malnutrition, renal failure, acute liver failure, presence of infection or
colonisation, and immune status for viruses like cytomegalovirus. In
recent years, it has become clear that genetic polymorphisms in innate
immunity contribute to the infection risk after liver transplantation.
Therefore, the risk for infections after liver transplantation is a
multifactorial problem and all factors need attention to reduce this risk
Early diagnosis and treatment are critically important in terms of
obtaining a better outcome defined as a reduced morbidity and mortality.
The diagnosis of invasive fungal infections is difficult because of the lack
of specific signs and symptoms until late in the disease process. Also,
Fungal Infection in Liver Transplant Patients
there is a difficulty with documenting a diagnosis with current diagnostic
tools, obtaining infected tissue required to establish a specific diagnosis,
and in some cases defining the isolated agent’s sensitivity to the
therapeutic regimen being utilized.
Currently available diagnostic tools for establishing a diagnosis of
an invasive fungal infection include the following: galactomannan, (1,3)-
β-glucan, and C. albicans germ tube antibody detection. Each of these
procedures has its own set of problems that limit their widespread
application. The uses of polymerase chain reactions (PCR) to detect
fungal DNAs are available in research laboratories but are not
standardized or FDA approved.
No consensus exists on which patients should receive antifungal
prophylaxis, when prophylaxis should be given, which antifungal agents
should be used, and what duration is effective. In patients at high risk for
invasive fungal infections, antifungal prophylaxis improves the survival
rate and quality of life in liver transplant patients.
Despite the availability of new antifungal drugs, the overall
survival for immunocompromised patients with invasive fungal
infections remains too low, with large variations according to underlying
disease. Factors that affect the choice of antifungal agent include
characteristics of the patient, the clinical circumstances, and the presence
or absence of overt sepsis and/or hemodynamic instability. Antifungal
drugs include Polyenes, Azoles, Fluorocytosine and echinocandins.
Fungal Infection in Liver Transplant
Polyenes include Amphotericin which has been the principal agent
for the treatment of invasive fungal infections for more than half a
century. Amphotericin is an accepted antifungal agent for C. albicans, but
has reduced activity against C. glabrata, C. krusei, C. lusitaniae, and
molds. Polyenes have not been shown to be of any value in prophylaxis.
The limiting factor for its use is nephrotoxicity.
Azoles is less toxic than the polyenes and can be administered both
orally and intravenously. Fluorocytosine is a pyrimidine analog that
inhibits both DNA and protein synthesis. Its principal use is in
combination with other agents for the treatment of cryptococcal
infections.
Echinocandins are semisynthetic lipopeptides that were isolated
originally from various fungal agents and subsequently modified. The
echinocandins have been shown to enhance phagocytic activity of
macrophages, an action that may also contribute to their efficacy in
eliminating fungal infections.
Antifungals are associated with diverse types of toxicities,
most commonly hepatic, renal, hematologic, electrolyte abnormalities
and infusion related. Amphotericin B preparations are related to
nephrotoxicity and infusion related reactions and the azoles are more
closely related to liver toxicities so close monitoring of their
immunosuppressive agents will be required. After discontinuation of
Fungal Infection in Liver Transplant
azole therapy, dose adjustment of immunosuppressive therapy is required
to prevent rejection.
The echinocandins are very safe with solid organ transplantation.
However, caspofungin has some minor interactions that requires dosing
adjustments. Micafungin appears to be safe and effective, but sirolimus
monitoring is recommended. Hepatic enzymes monitoring with the
echinocandins, in liver transplantation is recommended. Drug interactions
with fluconazole should be monitored. However, long-term fluconazole
is a relatively safe drug for use in SOT recipients.