Chapter 27: Infections in Liver Transplantation

INTRODUCTION: KEY POINTS

• Infections are an important cause of morbidity and mortality in liver transplant recipients. It is the leading cause of death in patients who have undergone liver transplantation.

Prior to transplantation:

• Identify potential infectious issues in both donors and recipients.

• Identify and evaluate both donors and recipients for past, present, and potential infections.

• Confirm that recipients are properly vaccinated.

Posttransplantation:

• Some early recipient infections may be donor derived.

• Recognizing the time course of infections provides useful information and should be carefully considered when predicting what infection may be present.

• Prophylaxis and treatment of acute rejection may alter or frame-shift the timeline of when specific infections are expected to occur.

• The severity of immunosuppression should be evaluated based on the patient’s:

  • Time from transplant

  • Type/dose of immunosuppression

  • Presence of recent rejection

  • Use of T-cell-inhibiting agents

  • Medical condition at the time of transplantation

DIAGNOSTIC POINTS

• Transplant recipients may present with altered inflammatory responses to infection.

• Common infections may present in uncommon ways.

• Clinicians must approach transplant patients with a high degree of suspicion for infection and consider that infection may be present until proven otherwise.

• Concurrent infections (more than one single pathogen) are more likely in transplant patients than in the general nonimmunocompromised population.

• The differential diagnosis of pathogens is more extensive in transplant patients than in nonimmunocompromised individuals.

• Have a low threshold for both enhanced imaging studies and biopsies. Imaging studies and biopsies should be obtained early in order to make a prompt definitive diagnosis and establish an adequate therapeutic approach—if in doubt, image and biopsy. Early diagnosis also helps limit the use of unnecessary empiric antimicrobials, some of which can be toxic and interact with other medications being used.

• It may be challenging to distinguish between colonization and active infection.

IMMUNOLOGIC DEFICIT: T-CELL INHIBITION LEADS TO INCREASED RISK OF OPPORTUNISTIC INFECTIONS

• Immunosuppression—although necessary to protect the transplanted liver from rejection—increases the risk of infections.

• Most immunosuppressive agents are associated with T-cell depletion, reduced T-cell activation, or inhibition of T-cell proliferation.

• The net result of immunosuppression is reduced cell-mediated immunity.

• Immunosuppression levels are generally greatest from month 1 to 6 posttransplant, as well as during any subsequent episodes of rejection that require intensified immunosuppression.

• Measurement of CD4+ T helper cells is not as predictive of opportunistic infections in transplant recipients as it is in patients with HIV/AIDS.

CLINICAL PREDICTORS OF POSTTRANSPLANT INFECTIONS

• Pretransplant variables that increase risk of infection posttransplant:

  • Age: older individuals are at greater risk of infections posttransplant.

  • Underlying liver disease: hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver cirrhosis, Child-Pugh score, Model for End-Stage Liver Disease (MELD) score.

  • Prior hepatobiliary surgery increases risk of infection in the early posttransplant period.

  • Intensive care unit (ICU) stay at any time prior to ...