Liver transplantation infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Liver trasnsplantation Microchapters
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Patient Information
Overview
Historical Perspective
Indications
Pre-surgical management
Choice of donor
Epidemiology and Demographics
Techniques
Complications
Acute rejection
Immune therapy
Post-surgical infection
Prognosis

Overview

Infection is the most frequent cause of death following liver transplantation. According to the timing, infection can be divided into three sections; First month after transplantation, 1 to 6 months after transplantation, and more than 6 to 12 months after transplantation. Prevention of infection includes Screening potential liver donors and recipients for infection, certain vaccines such as pneumococcal and influenza vaccines should be repeated after transplantation in an attempt to lower the risk for these diseases. Empiric broad-spectrum antibiotics should be initiated if a bacterial infection is suspected in a liver transplant recipient until the specific bacterium and its sensitivities can be identified. Antibiotic regimens should include coverage for gram-positive cocci, gram-negative bacilli and anaerobes. In patients without sulfonamide allergy, trimethoprim-sulfamethoxazole is generally administered for 6 to 12 months after liver transplantation to reduce the risk of pneumocystis jirovecii pneumonia, listeria monocytogenes, nocardia, and toxoplasma gondii. Prophylaxis of CMV includes Ganciclovir and valganciclovir are used to prevent CMV infection in patients at risk of CMV reactivation for three to six months. Prophylaxis of candida includes Fluconazole 400 mg orally daily is the drug of choice for one to four weeks or for as long as risk factors persist. Prophylaxis of aspergillosis includes Fluconazole prophylaxis decreased invasive fungal infections by 75 percent.

Liver transplantation infection

• Infection is the most frequent cause of death following liver transplantation.
• The most common types of infection were bacterial, fungal, and viral.
• Infections that are derived from donor organ tissues and activated in the recipient are among the most important exposures in transplantation.
• Infection associated with organ transplantation include mycobacterium tuberculosis, candida, aspergillus, herpes simplex virus, human herpes virus 8, lymphocytic choriomeningitis virus, rabies virus, trypanosoma cruzi, balamuthia mandrillaris, encephalitozoon cuniculi, HIV, and hepatitis C virus.

Timing of infection

First month after transplantation

• Endemic infections should be considered in the differential diagnosis of post-transplant infection.

• Liver transplant recipients develop many of the common postoperative infections such as aspiration pneumonia, surgical site infections, or urinary tract infection.
• These patients are at increased risk for infection associated with indwelling vascular access catheters, urinary catheters, and surgical drains.
• The organisms responsible for such postoperative complications are often the bacteria and fungi of the local flora of the hospital.
• Infections acquired before transplantation include relatively resistant nosocomial pathogens and pathogens such as aspergillus spp that are resistant to the usual prophylactic agents.
• Patients at particular risk of nosocomial infection are:
• Patients with prolonged ventilation
• Persistent ascites
• Patients with ischemic graft tissue
• Patients receiving antimicrobial agents are at increased risk for C. difficile colitis

1 to 6 months after transplantation

Major infections due to opportunistic pathogens include:

• Bacterial: tuberculosis and nontuberculous mycobacteria

• Protozoal disease: toxoplasmosis, leishmaniasis, and Chagas disease
• Fungal infections: histoplasma capsulatum, coccidioides and cryptococcus
• Viral infection: herpes virus, hepatitis B and hepatitis C
• Respiratory viruses: influenza, parainfluenza, respiratory syncytial virus, adenovirus, and metapneumovirus.

More than 6 to 12 months after transplantation

• LT patients are susceptible for community-acquired pneumonias due to respiratory viruses, pneumococcus, legionella, influenza, or listeria monocytogenes.
• Colonization with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus can lead to posttransplant infection with these organisms.

Prevention and treatment

Methods of infection prevention in LT patients:

• Screening potential liver donors and recipients for infection
• Appropriate vaccinations before transplantation
• Certain vaccines such as pneumococcal and influenza vaccines should be repeated after transplantation in an attempt to lower the risk for these diseases.
• Live vaccines should be avoided in transplant recipients due to the risk of disseminated disease.

Bacterial infection

• Empiric broad-spectrum antibiotics should be initiated if a bacterial infection is suspected in a liver transplant recipient until the specific bacterium and its sensitivities can be identified.
• Antibiotic regimens should include coverage for gram-positive cocci, gram-negative bacilli and anaerobes.
• The bloodstream, surgical wounds, and the urinary tract are common sites for primary infection, which may then disseminate.
• Clostridium difficile colitis can also occur, particularly in the early period following transplantation and in patients requiring prolonged hospitalization. Liver transplantation has been identified as a significant risk factor for C. difficile infection in the hospital.
• Pseudomonas aeruginosa and enterobacter species may be recovered from bronchoalveolar lavage specimens.
• Other common bacterial pathogens associated with pneumonia include Staphylococcus aureus, Klebsiella pneumonia, Stenotrophomonas maltophilia, and Citrobacter freundii.

Pneumocystis jirovecii

• Antibiotics are administered at transplantation in an attempt to prevent SSIs, including wound and intraabdominal infection.

• In patients without sulfonamide allergy, trimethoprim-sulfamethoxazole is generally administered for 6 to 12 months after liver transplantation to reduce the risk of pneumocystis jirovecii pneumonia, listeria monocytogenes, nocardia, and toxoplasma gondii.
• One single-strength tablet is taken daily or one double-strength tablet is taken three times weekly.
• The most common side effect of trimethoprim-sulfamethoxazole is allergy and myelosuppression.

Cytomegalovirus (CMV)

• Liver transplant recipients who are seronegative for CMV and receive an organ from a CMV-seropositive donor have the highest risk for developing CMV disease.
• CMV-seropositive recipients have a modest risk.
• CMV-seronegative recipients have the lowest risk.
• CMV infection has been associated with an accelerated course of hepatitis C virus recurrence.
• As a result, the incidence of CMV disease in the post-transplant setting has declined.
• Prophylaxis: Ganciclovir and valganciclovir are used to prevent CMV infection in patients at risk of CMV reactivation for three to six months.
• CMV prophylaxis reduced the risk of biopsy-proven rejection in liver transplant recipients.
• Treatment: Valganciclovir, at doses of 900 mg daily is the main drug for treatment.

Candida

• Candida is the predominant fungal infection encountered after liver transplantation.
• Candida prophylaxis for adult liver transplant recipients with ≥2 of the following risk factors include:
• Prolonged or repeat operation
• Retransplantation
• Renal failure
• High transfusion requirement
• Choledochojejunostomy
• Candida colonization during the perioperative period
• Prophylaxis: Fluconazole 400 mg orally daily is the drug of choice for one to four weeks or for as long as risk factors persist.

Aspergillus

• Aspergillus infections occur in patients with certain risk factors.
• Risk factors for Aspergillus infection after liver transplantation include fulminant hepatic failure, reoperation, retransplantation, renal or hepatic failure, cytomegalovirus infection, hepatitis C infection, and high-dose glucocorticoids.
• Mortality of aspergillosis in early series of liver transplant recipients approached 100 percent.
• Nosocomial pneumonias are particularly frequent in patients who require prolonged mechanical ventilation.
• The most common site of aspergillosis is the lung.
• It is the most common cause of CNS infection in liver transplant recipients, accounting for 55 percent of brain abscesses.
• Prophylaxis: Fluconazole prophylaxis decreased invasive fungal infections by 75 percent.

After six months

• Opportunistic infections are uncommon beyond six months post-transplant in patients who have good graft function since immunosuppression usually get tapered.
• These patients usually develop the same types of community-acquired infections seen in the general population, although at an increased rate.
• Transplant recipients may be more susceptible to some pathogens such as Legionella [103] and may experience more severe manifestations of certain infections such as West Nile virus infection.
• Patients on chronic immunosuppression often initially have only subtle findings of infection due to attenuation of inflammatory responses by immunosuppressants, but this may be followed by a precipitous decline in status and severe manifestations of infection. Respiratory infections due to pathogens such as Streptococcus pneumoniae and Haemophilus influenzae can be life threatening if not promptly treated. Patients who have chronic rejection are also more susceptible to chronic viral infections, possibly from the increased immunosuppressive regimens.
• Chronic or recurrent viral infections including those due to EBV, CMV, hepatitis B (HBV), hepatitis C (HCV), and human herpesviruses 6 and 7 also can lead to complications in the late posttransplant period.
• Chronic viral infections such as HBV and HCV can also produce damage to the liver allograft.
• Secondary tumors can occur also, especially posttransplant lymphoproliferative disease due to EBV and hepatocellular carcinoma due to HBV or HCV.
• Hepatitis E virus can also cause chronic hepatitis in liver transplant recipients and should be considered in patients with unexplained liver enzyme elevations.