Mini review
Vaccination in adult liver transplantation candidates and recipients

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Summary

In patients with chronic liver disease and liver transplant recipients, cirrhosis-associated immune dysfunction syndrome and immunosuppressant drug regimens required to prevent graft rejection lead to a high risk of severe infections, associated with acute liver decompensation, graft loss and increased mortality. In addition to maintain their global health status, vaccination represents a major preventive measure against specific infectious risks of particular concern in this population, such as invasive pneumococcal diseases, influenza or viral hepatitis A and B. However, immunization in this setting raises several issues: i) recommended vaccination schedules rely on sparse immunogenicity data without clinical efficacy and effectiveness trials designed for this specific population; ii) dynamics of immunosuppression makes timing of immunization challenging; iii) live attenuated vaccines are contraindicated after transplantation; and iv) vaccines tolerance is poorly known in cirrhotic patients. This review outlines the rational for vaccination in adult liver transplant candidates and recipients and available data regarding immunization in this specific population.

Introduction

Chronic liver disease is associated with an overall impairment of the immune system, referred as cirrhosis-associated immune dysfunction syndrome, leading to an increased risk of infections which represent a major cause acute liver decompensation and mortality [1], [2]. Liver transplantation (LT) currently represents the main therapeutic option for end-stage liver disease and localized hepatocellular carcinoma. The risk of infection increases in the pre-transplantation period with the severity of liver disease, and is maximal during the 6 first months post-LT due to intensive immunosuppressive drugs regimens used to prevent graft rejection [3]. In addition, to maintain the global health status of cirrhotic patients and LT recipients as in general population, vaccination represents a pivotal preventive measure against infections of particular concern in this population, including invasive pneumococcal diseases (IPD), influenza or viral hepatitis A (VHA) and B (VHB). However, current guidelines rely on very little data regarding vaccine efficacy and effectiveness in this specific population [4], [5], [6], [7]. Additionally, the establishment of immunization schedules is challenging, having to take into account the balance between a decreased efficacy of vaccines in immunosuppressed hosts, an accelerated loss of antibody titers, the dynamics of immunosuppression in the peri-transplantation period, and the contraindication of live attenuated vaccines after LT.

The present review summarizes the rational for immunization in the peri-LT period, focusing on risk evaluation and available data regarding vaccine efficacy in this specific population.

Section snippets

Immune status of patients with chronic liver disease and after transplantation

Cirrhosis–and a fortiori liver failure–is associated with an overall dysfunction of the immune response [2], responsible for an increased infection risk, related to:

  • a destruction and shunt of the intrahepatic reticuloendothelial system, impeding bacterial and toxin clearance;

  • a disturbed innate immunity, with impairment of mobilization, phagocytic functions and half-life of neutrophils and monomacrophagic cells, and of hepatic synthesis of the components of the complement system; and

  • a

General principles of vaccination in the setting of solid organ transplantation

With respect to vaccine-preventable diseases, patients awaiting LT share issues of all immunosuppressed hosts:

  • an increased incidence and severity of several vaccine-preventable infections requiring specific immunization recommendations;

  • a decreased immunogenicity of vaccines and an accelerated loss of protection, which may require specific vaccination schedules with additional booster doses; and

  • a contraindication of live attenuated vaccines after transplantation given the risk of active

Invasive pneumococcal diseases

IPD are more frequent and more severe in cirrhotic patients [23], [24]. Lower respiratory tract infections are the third leading cause of infection in this population, the main etiologic agent being Streptococcus pneumoniae. Community-acquired pneumonia during cirrhosis is more frequently bacteremic, multi-lobar, associated with neurological, renal or multi-organ failure, and complicated by septic shock [25]. Globally, the mortality rate is 2 times higher than in the general population. Beyond

Conclusion

Chronic liver disease patients and LT recipients are at increased risk of infections, some of them being preventable by vaccination, especially IPD, influenza, viral hepatitis A and B, measles and chickenpox and HZ. National and international guidelines have been released regarding immunization of LT candidates and recipients. However, knowledge on vaccine response in this specific population is scarce and there is a need for specific trials evaluating vaccine efficacy. While the tolerance of

Disclosure of interest

The authors declare that they have no competing interest.

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