Isolated Liver Transplantation in Children With Intestinal Failure–associated Liver Disease: A Still‐debated Matter

Abstract

Although combined liver and small bowel transplantation is considered a lifesaving treatment option for children with intestinal failure and associated liver disease (IFALD), the survival rate of children undergoing combined liver and small bowel transplantation is low, with a mortality rate of 65% at 6 months (1–6). However, compared with isolated small bowel transplantation, combined transplantation is associated with better intestinal graft survival and a lower incidence and severity of rejection (7–9). In particular, there is a lower incidence and severity of acute intestinal graft rejection in recipients of combined transplantation than in recipients of isolated small bowel transplantation, probably as a consequence of immune tolerance induced by the liver. Liver failure is a frequent indication for combined transplantation in children with intestinal failure (6). In other words, if intestinal failure–associated liver disease needs liver transplantation, then it also represents one of the criteria to select candidates for intestinal transplantation (8,9). The impact of isolated liver transplantation (iLTx) on the survival and quality of life of patients with intestinal failure and associated liver disease is unclear (10–13). In this issue of JPGN, Gupte et al report that iLTx may be lifesaving for selected children with short bowel syndrome and IFALD. The authors propose new criteria for iLTx in children with intestinal failure–associated liver disease. In their experience, 9 (64%) out of 14 children receiving iLTx were alive after a median of 35.6 months (range 21.2–86.8 months), and 8 of them were successfully weaned from parenteral nutrition (PN) after a median of 15 months. If these patients had received a combined liver–intestinal transplant rather than iLTx during the same period of time, most of them would have died, on the basis of available survival rates. Presently, iLTx should be considered for children who are expected to be weaned from PN, such as those with a reasonable bowel length or function (14). Although definitive criteria for ILTx in PN-associated end-stage liver disease (ESLD) are not established, it is clear that the length and function of residual bowel play a significant role in establishing whether intestinal failure may be reversible. In patients with severe motility impairment or absorptive disorders, full adaptation is unlikely and combined transplantation could be considered. Intestinal function may improve after iLTx because the degree of portal hypertension and bowel edema at the time of iLTx could have contributed to the pretransplant intolerance to enteral feeds (14). In some patients with intestinal failure who received iLTx, intestinal function had eventually improved before iLTx. It has been proposed that predictors of successful bowel adaptation and future weaning from PN should be detected before iLTx. This is not supported by concrete data (15–18). The promising results of iLTx have been overshadowed by high complication rates in recipients of isolated liver transplant with intestinal insufficiency. The postoperative course is associated with higher rates of infections, vascular, biliary, and surgical complications compared with liver transplants for other indications (19,20). A major potential problem of patients with intestinal failure receiving iLTx is the intestinal absorption of antirejection drugs; it has been reported that therapeutic levels of these drugs may be achieved in these patients in the postoperative period (19–21). A further debated matter is the financial burden associated with iLTx in patients with intestinal insufficiency. The complications in the posttransplantation period contribute to the high costs, as do extended hospital and lengthy stays in the intensive care unit. Parenteral nutrition also increases the already heavy posttransplantation costs. These costs need to be balanced against the cost of complications and hospitalizations for these patients during the waiting period for combined liver and intestinal transplantation. Because these patients may not undergo intestinal transplantation and thus have better long-term outcomes and survival, the cost on the front end may well be justified (19–21). It is necessary to understand whether iLTx or combined transplantation should be used for PN-associated ESLD. Registry databases must be established to understand the clinical course of PN-associated ESLD patients and thus help to define the indication for the application of iLTx compared with combined transplantation in this particular population (22–27). The paper by Gupte et al offers precious information in this sense. In conclusion, the outcome of iLTx in patients with intestinal failure and PN-associated ESLD is better than the outcome of patients who undergo either isolated intestinal transplantation or combined liver and small bowel transplantation. Isolated liver transplantation may improve intestinal adaptation, thereby overcoming the need for small bowel transplantation in selected patients. Overall, when we look at survival rates in relation to the therapeutic options in this population, outcome is best with iLTx (Fig. 1).FIG. 1: Possible options and relative outcomes for children with intestinal failure on PN. Intestine transplantation: http://www.medscape.com/viewarticle/436543_1.