**9.2. Chronic rejection**

Immunosuppression regimen varies, with several protocols having been reported: Tacrolimus and steroids (35.8%) followed by tacrolimus, mycophenolate and steroids (18.7%), tacrolimus and mycophenolate without steroids in 15.4% of cases and tacrolimus alone in 13.8% of cases [38]. Target trough levels of tacrolimus vary between centers. Pittsburgh has reported target levels between 10 and 15 ng/ml in the first 3 months and thereafter 5–10 ng/ml [39]. Tacrolimus with low-dose steroids remains the most effective and durable long-term combination therapy [21]

Sirolimus, a rapamycin inhibitor, has been shown as a useful adjunct to tacrolimus in the presence of nephrotoxicity or rejection [40]. However, it carries the disadvantage of severe debilitating oromucosal ulceration. Azathioprine and mycophenolate mofetil have also been used as adjunctive immunosuppressive therapies [33]. Mycophenolate mofetil, however, causes symptomatic diarrhea (increased stoma output) and microscopically evident apoptosis in approximately 40% of solid organ transplant recipients, which could regrettably be

Complications following ITx may result in graft failure and invariably death. Patients undergoing ITx have a higher incidence of life-threatening infectious complications than other transplant recipients. This is due to the high bacterial load of the transplanted graft [42]. Therefore, any breach to the intestinal transplant mucosal barrier can lead to bacterial translocation.

Graft loss would need TPN resuming and consideration of re-transplantation, which has a lower rate of success compared with the initial transplantation [43]. Common causes of graft loss include allograft rejection, infection, GVHD and post-transplant lymphoproliferative dis-

Allograft rejection has always been one of the most significant challenges to long-term graft and patient survival and can occur either as acute (commonly in the early phase, though can occur late) or chronic (typically taking months to years). Rejection can occur at any time but is most common in the first year, particularly the first 6 months. It affects 45% of ITx patients within the first post-transplant year, with implications on graft survival [7] and is mostly

Acute rejection should be suspected in all cases of bowel dysfunction (increased stoma output) and symptoms include fever, vomiting, abdominal pain and distension. Diagnosing acute rejection is always challenging and requires a combination of clinical, endoscopic and histopathological investigations. Intestinal allograft endoscopy and biopsies is the gold standard. However, diagnosis can be difficult to establish because of the patchy nature of rejection. Not to mention, that it is not always easy to differentiate between rejection and infection.

and is the most common maintenance immunosuppressive regimen [7].

300 Organ Donation and Transplantation - Current Status and Future Challenges

mistaken for rejection [41].

**9. Complications**

order (PTLD) [33].

**9.1. Acute rejection**

characterized by T-cell response to donor antigens.

Chronic rejection is diagnosed histologically with the identification of an obliterative arteriopathy in medium-sized vessels in the serosal layer with diffuse concentric intimal thickening [55]. This necessitates full-thickness biopsy and makes diagnosis challenging. Chronic rejection is clinically associated with diarrhea, ulceration, focal loss of mucosal folds, mural thickening and pruning of mesenteric artery arcades [55]. Surgery in such a hostile environment may lead to unwanted enterotomies and fistulae. Re-transplantation should therefore 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-transplantation [56].

It is believed that in ITx, the lymphatic-rich intestinal allografts in combination with splenectomy and immunosuppression pose an increased risk for PTLD [68]. It has been reported that the presence of PTLD has significantly reduced patient survival within the first posttransplant year [69]. PTLD is treated with immunosuppression reduction and rituximab con-

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http://dx.doi.org/10.5772/intechopen.74825

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

Treatment strategies vary and most frequently involve tacrolimus, high-dose steroids or

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

Patient survival has been steadily improving because of improved first-year graft survival [7]. Graft survival has been reported for 1, 5 and 10 years at 74, 42 and 26%, respectively (SBTx); 70, 50 and 40% (MVTx); 61, 46 and 40% (SBLTx); overall patient survival was 76, 56 and 43%, respectively. Studies evaluating 1-year and 5-year patient survival rates at various transplant

Patients on TPN have 1-year, 5-year, 10-year and 20-year survival of 91–93, 70–71, 55–59 and 28%, respectively, following IF commencement [77]. It should be noted, that 11–15% of deaths while on TPN were attributed to TPN complications (5–6% from sepsis or central-line sepsis and 6–9% from IFALD) [77]. A three-year prospective study reported 94 vs. 87% threeyear survival in TPN non-transplant candidates vs. TPN transplant candidates who did not undergo transplantation. In addition, the three-year survival was 89 vs. 85 vs. 70% for those having first SBTx vs. transplant candidates with central venous catheter complications vs.

taining chemotherapy regimes in the presence of CD20 positive cases [70].

or native liver dysfunction. Diagnosis is confirmed by skin or bowel biopsy.

receive renal replacement therapy by a median of 7.4 years [74].

candidates with parenteral nutrition-related liver failure [78].

**9.6. Graft versus host disease**

anti-thymocyte globulin (ATG) [71].

**10. Graft and patient survival**

centers revealed comparable results [75, 76].

**9.7. Renal dysfunction**

#### **9.3. Donor-specific antibodies**

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 DSA formation.
