Combined Liver and Small Bowel Transplantation

Intestinal Failure

IF is the reduction of functional gut mass below the threshold of maintenance of metabolic functions in adults and normal growth in children. The treatment of choice of irreversible IF is home parenteral nutrition (PN), for which mortality in children is very low. IF is a rare disease; the patients’ care should therefore be shared (whether physically or via web consulting) with an expert center for intestinal rehabilitation, where all medical and surgical options can be discussed.

ITx is the treatment of total and irreversible IF, associated with life-threatening complications of PN. The child should receive at least 80% of his nutritional needs in PN without any hope of future weaning of PN.

IF is obviously definitive if the child has ultrashort bowel syndrome or severe microvillous inclusion disease. However, intestinal adaptation may be possible in not-so-short bowel syndrome, and the evolution of IF is variable in other enteropathies or chronic intestinal pseudo-obstruction syndromes (CIPOSs).

Causes of Intestinal Failure

• a-

  Short bowel syndrome, the most frequent indication in the ITR (61%): intestinal atresia, necrotizing enterocolitis, gastroschisis, volvulus, desmoid tumor;

• b-

  Mucosal diseases or congenital enteropathies (9% in the ITR): microvillous inclusion disease, tufting enteropathy; and

• c-

  Motility disorders (19% in the ITR): long-segment Hirschsprung disease, chronic intestinal pseudo-obstruction syndrome (CIPOS).

Complications of Home Parenteral Nutrition Limiting Its Long-Term Performance

• a-

  Loss of vascular access: the number of thrombosed major veins is discussed (two in the first criteria, number recently challenged ), but it should not wait until the last central line. Care of central lines, size, location, insertion, and management should be meticulous in patients with IF.

• b-

  Recurrent or life-threatening infections from the central line or the digestive tract. Taurolidine or ethanol locks can be discussed, and continuous training of staff and caregivers is essential.

• c-

  Progressive IF-associated liver disease (IFALD): ITx should be discussed before complications of cirrhosis such as bleeding. Prevention of IFALD is important from the onset of IF: preservation of the enterohepatic cycle and gut motility, prevention of infections, adequate and cycled PN, and control of fat emulsions.

• d-

  Severe hydroelectrolytic disorders because of major digestive losses, such as in microvillous atrophy.

• e-

  Growth failure despite adequate calorie supply.

• f-

  Inability to perform PN at home for social or medical reasons; ITx should be discussed before the development of irreversible psychological disorders.

• g-

  Psychological intolerance to home PN: this is the most difficult indication. Patients and families see ITx as the relief of PN constraints (“dog on leash”) and hear only part of the ITx ones (“leash is transparent”). But if home PN is unbearable, it will be inadequately managed, with new complications. Repeated explanations and time should be given.

General Evaluation

The timing of referral for ITx is critical, and early dialogue with an ITx center is recommended. Waiting times are long, and the children should be referred before severe complications threaten their lives in the short term. On the waiting list for ITx, close collaboration between centers should be maintained and PN perfectly monitored, as additional complications may impair the outcomes.

The evaluation is the same as for another organ transplantation. However, some particularities are unique, such as the small numbers of centers, which are present in certain countries only. Even more than other organ transplantations, ITx is not a cure, and long-term complications are frequent. ITx should reasonably not be performed if the follow-up is not secured.

The psychosocial evaluation is an important part for families with difficult histories and more difficult weeks or months of hospitalization ahead.

Kidney Function

The glomerular filtration rate (GFR) should be measured (iohexol, Chrome EDTA [CrEDTA], etc.), and not calculated. The pre-ITx risk factors for renal failure are many: pre-existing disease (Hirschsprung and renal dysplasia, CIPOS and megacystis, microvillous inclusion disease and dehydration, etc.), antibiotics, and so on. After ITx, these are immunosuppressive drugs, antibiotics, and hemodynamic or septic shock. If the GFR is below 50 mL/mn/1.73m ² , a combined kidney transplantation may be discussed.

Infections

Patients often harbor multiresistant bacteria. Bacterial and fungal screens should be repeated during the waiting time and antibiotics spared if possible. The child should receive all vaccines, especially live ones, that cannot be given after ITx.

Anti–Human Leukocyte Antigen Immunization and Immunological Risk

Pre-ITx antihuman leukocyte antigen (HLA) immunization is frequent in these patients who were multioperated. In many countries the waiting time is too long for a pre-ITx desensitization, whose efficiency is not demonstrated. For combined liver–small bowel ITx, because of organ shortage and lower risk of post-ITx humoral rejection, the decision to accept the graft does not depend on HLA. An isolated intestine, however, should not be accepted if the recipient has pre-ITx donor-specific antibodies (DSAs). The prevention of humoral rejection post-ITx follows the same protocols as for kidney transplantation: screening for DSA, intravenous immunoglobulins, and plasma exchanges if DSAs appear or increase.