**9.6. Graft versus host disease**

be considered. Evisceration is a potential life-saving option for ITx patients who developed severe rejection, and has similar survival rates with patients who underwent simultaneous enterectomy with re-transplantation; however, high sensitization may prevent re-transplan-

Preformed and de-novo DSAs have been associated with acute rejection and may be implicated in chronic rejection and graft loss [46, 57]. Five-year graft survival of less than 30% was noted in ITx patients who developed de-novo DSA, whereas survival rates of more than 80% were observed in recipients without DSA [44]. Yet, others have not found a statistically significant trend towards worsening outcomes [58] between those with or without de-novo

The use of immunosuppression in ITx poses a significant risk of infection and, historically, high levels of immunosuppressants have been utilized in ITx. Sepsis remains the most common cause of death and graft failure, accounting for over 50% of cases [7]. Bacterial infections are common in the early phase post-ITx and have a significant impact on patient survival.

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viraemias are common and can be implicated in acute and chronic rejection as well as PTLD [60, 61]. CMV status is vital to anticipate the risk of developing de-novo infection in a non-infected recipient from the donor and through reactivation of a latent infection. CMV prophylaxis with oral valganciclovir is often continued for 1 year following ITx [62]. Most programs would not accept CMV-positive donors for CMV-negative recipients as this is high risk and should be avoided [63]. Last but not least, it has been demonstrated that isolated graft CMV disease without overt CMV virae-

In the updated 2016 WHO lymphoma classification, PTLD has been sub-classified as plasmacytic hyperplasia PTLD, infectious mononucleosis PTLD, florid follicular hyperplasia PTLD, polymorphic PTLD, monomorphic PTLD and classical Hodgkin lymphoma PTLD [65]. PTLD following SOT occurs in up to 20% with the highest incidence in intestinal and multi-organ transplants (5–20%), followed by lung and heart transplants (2–10%) and then by renal and

About 70% of cases of PTLD are associated with Epstein-Barr virus (EBV), especially in cases which occur early after transplantation. Pathogenesis of the disease is linked to EBV proliferation in the setting of chronic immunosuppression leading to an inhibition of T-cells immune function. However, in 30% of EBV-negative PTLD patients, pathogenesis is not clearly under-

Invasive candidiasis has been reported as the commonest fungal infection [59].

tation [56].

DSA formation.

**9.4. Infection**

mia can indeed occur [64].

liver transplants [66].

stood [67].

**9.5. Post-transplant lymphoproliferative disorder**

**9.3. Donor-specific antibodies**

302 Organ Donation and Transplantation - Current Status and Future Challenges

The small intestine has abundant lymphoid cells that can mount an immunologic response to the host (i.e. a graft versus host disease [GVHD]) reaction. GVHD occurs in 5–7% of intestinal transplants, compared to 1% for solid organ transplants, and risk factors include younger age, MVTx recipients and intra-operative splenectomy [71]. It is more common in intestinal transplants due to the large volume of lymphatic tissue that is transplanted along with the graft. GVHD diagnosis is allegedly difficult to establish and patients usually present 1–8 weeks after transplantation with skin rash, ulceration of oral mucosa, diarrhea, lymphadenopathy or native liver dysfunction. Diagnosis is confirmed by skin or bowel biopsy.

Treatment strategies vary and most frequently involve tacrolimus, high-dose steroids or anti-thymocyte globulin (ATG) [71].

#### **9.7. Renal dysfunction**

Renal dysfunction is invariably seen post ITx due to a combination of high-dose tacrolimus therapy [72] and dehydration episodes, especially in the presence of stomas. The incidence of stage 4 or 5 CKD is 21.3% in patients with ITx [73] and approximately 9% of ITx patients will receive renal replacement therapy by a median of 7.4 years [74].
