Infections After Liver Transplant -Timeline, Management and Prevention

Abstract

Liver transplantation (LT) is the standard treatment for end- stage liver disease. Patient and graft survival have improved significantly in the last three decades owing to improvement in surgical technique, better perioperative management and better immunosuppressive regimens. However, LT recipients are at increased risk of infections, particularly in the first year after transplantation. The risk of infection is directly proportional to immunosuppressive regimen and graft function. In this review, we will briefly discuss the timeline of infections after liver transplant, preventive strategies and management of infectious complications.

Keywords: immunosuppression; infection; liver transplant; multi-drug-resistant infections; timeline.

Graphical abstract

Figure 1

Tacrolimus/Cyclosporin absorption, metabolism and disposition. Concentration of calcineurin inhibitors (Tacrolimus/ Cyclosporin A) is regulated by P-glycoprotein [P-gp] and cytochrome P 450 enzymes (CYP 3A4 and CYP 3A5). Efflux transporter P-glycoprotein plays a major role in pharmacokinetics of Tacrolimus and Cyclosporin. P-gp pumps both drugs out of enterocyte into intestinal lumen and lowers intracellular and systemic concentration of both drugs. Drugs which induce P- gp (Rifampicin) reduce bioavailability of both these agents. Inhibitors of P- glycoprotein (e.g. grapefruit juice) increase bioavailability both drugs. P-gp also transports drugs across membranes within hepatocytes. However, its role within the enterocyte is better characterized. CYP3A5 is the predominant enzyme for metabolism of Tacrolimus whereas Cyclosporin A is primarily metabolized by CYP 3A4. Both Tacrolimus and Cyclosporin A are extensively metabolized with less than 0.5 % and 1 % respectively, of the parent drug appearing unchanged in urine and feces. Enzyme inducers (Rifampicin, Rifabutin) decrease drug levels of Tacrolimus and Cyclosporin, whereas enzyme inhibitors (Azoles, Macrolides) increase drug levels [Table 5]. Genetic polymorphisms of the P-gp and CYP enzymes have been recently defined, and these define the C0/D [concentration to dose ratio] in a given patient. This may provide an opportunity to offer personalized immune-suppression to solid organ transplant recipients in future, thus mitigating side-effects.

Figure 2

Algorithm for antimicrobial use in post- LT patients. Infections in liver transplant recipients are a function of pre-operative risk factors, intra-operative and post-operative events. Antimicrobials therapy in post-LT period should be based on these factors.