Overall Bottom Line
- The prevention of bacterial, fungal and viral infections after LT is essential to successful outcomes.
- Early recognition of infection is essential for implementing the appropriate treatment strategy and improving outcomes.
- Early consultation with a transplantation infectious diseases specialist is recommended.
Section 1: Background
Disease classification
- Infections in the LT recipient can be classified by community vs hospital acquisition; newly acquired vs reactivation of latent infection; or the type of pathogen (e.g. bacteria, fungi, virus, etc.).
Incidence/prevalence
- Incidence and prevalence of infectious complications can vary depending on type of donor (deceased vs living); type of immunosuppression; local and regional epidemiologic factors; and other donor factors. Bacterial infections are the most frequent infectious complication.
Etiology
- Hospital-acquired.
- Community-acquired.
- Reactivation of latent viral, fungal and mycobacterial pathogens.
- Donor-derived.
Pathology/pathogenesis
- In the first month after transplantation, the pathogenesis of infectious complications is similar to other post-surgical patients and is predominantly healthcare-associated infections. From approximately 1–6 months following transplantation, immunosuppression is most intense and during this period, opportunistic infections in the setting of weak cell-mediated immunity can occur. Following this period, infectious complications are significantly reduced and are similar to community-acquired infections in the general population.
Predictive/risk factors
| Type of infection | Risk factors |
|---|---|
| Bacterial |
|
| Fungal |
|
| CMV |
|
Section 2: Prevention
Bottom Line/Clinical Pearls
- Prophylaxis strategies to prevent bacterial, fungal and viral infections after LT are considered standard of care.
- Although studies to support peri-operative antibacterial prophylaxis are lacking, it is widely accepted as standard practice in LT.
- Clinical studies support strategies to prevent CMV disease in LT recipients.
- Clinical studies support targeted antifungal prophylaxis in high-risk LT recipients.
Screening
- Blood tests to identify patients at risk for infections are routinely performed in LT candidates:
- CMV IgG.
- EBV IgG.
- Varicella IgG.
- HIV-1/2 ELISA.
- Hepatitis A IgG.
- HBsAg.
- Antibody to HBsAg (anti-HBs).
- Anti-HBc.
- Antibody to hepatitis C.
- Rapid plasma reagin.
- Strongyloides stercoralis IgG (for patients from endemic regions only).
- CMV IgG.
Primary and secondary prevention
- The following vaccines are recommended for any susceptible LT candidate as early as possible prior to transplantation. It should be noted that vaccine response is poor in patients with advanced liver disease:
- Influenza (and annually thereafter).
- Pneumococcal polysaccharide vaccine.
- Hepatitis A.
- Hepatitis B.
- Varicella (should not be administered after transplantation).
- Tetanus.
- Polio (inactivated).
- Influenza (and annually thereafter).
- Bacterial prophylaxis is provided to all patients peri-operatively for 24 hours. Ampicillin/sulbactam is acceptable in most cases. A modified regimen should be considered in the setting of penicillin allergy or colonization with resistant pathogens.
- Viral prophylaxis is provided to all patients for approximately 3 months to prevent CMV and other herpes viruses. Oral valganciclovir is given if the donor or recipient is CMV seropositive. Oral valacyclovir is given if the donor and recipient are seronegative.
- Antifungal prophylaxis is recommended in high-risk situations such as re-transplantation, fulminant hepatic failure and renal failure. Fluconazole is generally used at least until the patient is clinically stable for up to 3 months after transplantation.
- Pneumocystis jiroveci pneumonia (PCP) prophylaxis is provided to all patients for at least 3 months after transplantation and should be considered lifelong, particularly in patients with ongoing rejection or graft dysfunction. Trimethoprim-sulfamethoxazole is the preferred agent. Dapsone and atovaquone are alternative agents.
- Testing for latent tuberculosis with tuberculin skin testing or IFN-γ-release assays should be performed in all LT candidates and recipients. Treatment should be considered either early prior to transplantation or once the patient is stable after transplantation.
Section 3: Diagnosis
Bottom Line/Clinical Pearls
- The diagnosis of infections in LT recipients is guided by three time periods after LT: 0–1 month, 1–6 months, and after 6 months.
- Most patients will present with fever but sometimes these clinical signs of infection are masked by immunosuppression.
- In the first period (0–1 months), the majority of infections are typical healthcare-associated infections in a surgical patient.
- In the second period (1–6 months), opportunistic infections can emerge in the absence of or after discontinuation of prophylaxis.
- In the third period (>6 months) the majority of infections will be typical community-acquired infections. However, in the setting of rejection and/or graft dysfunction, the risk for healthcare-associated and opportunistic infections can persist.
Clinical diagnosis
0–30 days (Algorithm 50.1)
- The majority of infections will be surgical site infections, pneumonia, catheter-related bloodstream infections, catheter-associated urinary tract infections and Clostridium difficile colitis. Although a detailed physical examination should always be performed, examination of the lungs, abdomen, wound and intravascular catheter sites are particularly essential.
- In the absence of targeted signs or symptoms, the initial evaluation should consist of at least blood cultures and chest X-ray. If there is a high clinical suspicion for pneumonia, a CT scan should be obtained if the chest X-ray is negative. Urinalysis and urine cultures should be obtained in patients with urinary symptoms or patients with an indwelling urinary catheter and unexplained fever and/or leukocytosis. Stool C. difficile PCR should be obtained in patients with diarrhea or unexplained abdominal pain.
- If there is no evidence for pneumonia, bacteremia, UTI, or C. difficile colitis and signs of infection (e.g. fever and/or leukocytosis) persist, then a CT scan of the chest, abdomen and pelvis should be obtained to identify a deeper surgical site infection or occult pleuro-pulmonary infection.
31–180 days (Algorithm 50.2)
- In addition to any of the infections that are commonly seen during the first month after LT, there should be a heightened suspicion for opportunistic infections during this period.
- CMV disease commonly occurs after prophylaxis has been discontinued particularly in donor positive, recipient negative (D+R-) patients.
- Fungal infections such as Aspergillus and Cryptococcus may be seen. Other miscellaneous opportunistic infections include Nocardia and tuberculosis.
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