Difficult Management Choices For Infants With Short Bowel Syndrome and Liver Failure

Abstract

Short bowel syndrome (SBS) exists when malabsorption occurs as a result of bowel loss (1). The main causes in children are intestinal atresias, gastroschisis, volvulus, and necrotizing enterocolitis (2–3). After massive bowel loss, the remaining bowel undergoes a process of adaptation that includes an increase in bowel diameter, mucosal villous height, and bowel length (4). The mainstay of management for children with SBS consists of well-monitored parenteral nutrition (PN), avoidance of infections, and dietary adjustments until a degree of intestinal adaptation compatible with life and sustained growth on enteral nutrition alone has been achieved (2). These objectives are most easily achieved at centers with an established nutritional care team (5,6). Unfortunately some infants develop serious complications (e.g., catheter-related sepsis, vascular access thrombosis, liver disease) before intestinal adaptation has occurred (7–14). This has encouraged the development of alternative modalities of treatment of which two main alternatives enable independence from PN. The first is the various nontransplant surgical procedures designed to improve intestinal function (2,10,15). Among those procedures is longitudinal isoperistaltic intestinal tailoring and lengthening (Bianchi procedure), first described in 1980 (16). Small series and case reports since then have suggested that most such patients improve within 3 to 9 months of the procedure, in terms of enteral feeding and ability to wean from PN (2,17–25). The second option is small bowel transplantation, which may be combined with simultaneous liver transplantation. This approach would appear to be the most logical solution to short bowel syndrome and its hepatic sequelae, but the highly immunogenic nature of the intestinal epithelium means that patients are maintained on high levels of immunosuppression. Increased exposure to immunosuppressant agents puts patients at risk for opportunistic infections, which can be fatal. Consequently, transplant teams have been circumspect in recommending intestinal transplantation, and in general only patients with life-threatening complications have been accepted in small bowel transplant programs (26,27). We report a case that illustrates a management dilemma in a patient with SBS who was dying of liver failure and propose a third option for treatment. CASE REPORT The patient is the second-born male child of white parents and was born in February 1998 at 33 weeks gestation by emergency caesarean section. He had gastroschisis and emergency surgery was performed on day 1 of life to return the intestine to the abdominal cavity. After surgery he remained unwell with metabolic acidosis, anuria, and ventilatory difficulties. A second laparotomy the following day showed that his small bowel was necrotic, and most of it was resected leaving only 19 cm of viable bowel between the pylorus and the intact ileocecal valve. An ileostomy was fashioned 5 cm from the ileocecal valve, and his condition stabilized. He began receiving parenteral nutrition (PN), and in addition various elemental and semi-elemental enteral feeds were tried but were poorly tolerated. He had recurrent central-line infections and progressive cholestasis. By the time he was transferred to our unit, at 4 months corrected age, his serum bilirubin concentration was 437 μmol/L and prothrombin time (PT) was 30 seconds (control, 9–13 seconds). His condition deteriorated rapidly, and within a week his bilirubin concentration increased to 618 μmol/L and the PT to 36 seconds. As no pediatric donor for combined liver and small bowel became available, a left lobe liver from a 65-kg adult donor was accepted 16 days after initial admission. The liver graft was reduced in size (donor:recipient weight ratio = 12), and the patient underwent an isolated liver transplantation. To maximize the residual small bowel, the biliary anastomosis was fashioned directly onto the patient's duodenum. He required 3 weeks of intensive care and a second laparotomy to close the muscle layer, due to the large mismatch in size between the donor organ and his abdominal cavity, but he eventually made a full recovery. He was reestablished on PN and was discharged to his local hospital 6 weeks later. During the next 12 months, no significant intestinal adaptation occurred because of vomiting and malabsorption when enteral feeds were increased in volume. At 16 months of age, he was readmitted for assessment of intestinal function. His weight was at the third centile, and height was below the third centile (Fig. 1). A barium meal and follow-through radiograph showed a dilated small bowel with no propulsive peristalsis (Fig. 2). Duodenal biopsy tissue showed partial villous atrophy but no inflammatory changes. After discussion, the Bianchi isoperistaltic intestinal lengthening procedure was performed when he was 2 years old. At this laparotomy, the length of the dilated small bowel was 30 cm with a diameter of 5 cm. It was divided and lengthened to 55 cm with a diameter of approximately 2.5 cm (Fig. 3). He was discharged to his local hospital 5 weeks later, tolerating enterally 80% of his daily calorie requirements (Nutramigen). He was weaned gradually from PN supplements, and 6 months later he was fully enterally fed. Currently, 18 months after the Bianchi procedure, he is well and fully established on oral feeds (Pediasure 600 mL/d) and the normal family diet, and his weight and height are satisfactory (Fig. 1). His development according to the Bayley scales is normal.FIG. 1.: Height and weight growth chart before and after surgical interventions.FIG. 2.: Barium contrast study at 16 months of age showing dilated nonpropulsive jejunum.FIG. 3.: Diagram of intestinal lengthening and tapering operation (the Bianchi procedure).DISCUSSION This patient experienced end-stage liver disease secondary to PN in less than 6 months. This unusually rapid evolution was related to a combination of preterm birth and recurrent sepsis. It was not clear at the time of referral whether he would ever become independent of PN despite retaining his ileocecal valve, as he had never tolerated enteral feeding. He was too ill to undergo a lengthening and tapering procedure. Therefore, he was assessed for a combined liver and bowel transplant, but he was extremely ill at a time of pediatric donor organ shortage. An isolated liver transplantation was performed as a lifesaving procedure and to allow time for the patient to become stable enough to benefit from other treatments that include 1) long-term home PN; 2) sequential small bowel transplant; 3) nontransplant surgery to improve intestinal function, for example, the Bianchi procedure. The Bianchi procedure appears to be most successful for those who have undergone a period of normal bowel adaptation after initial bowel resection and in whom adaptation has stopped or regressed. Bianchi (23) advocated this principle, and deviation from this approach, by using the procedure at the time of initial bowel resection, has resulted in poor outcome (24). Correction of liver dysfunction by isolated liver transplantation may be an option if a patient has liver failure and has the potential for either natural bowel adaptation or undergoing future bowel reconstruction procedures, such as longitudinal intestinal tailoring and lengthening. When liver failure and cholestasis ensue before independence from PN, a vicious cycle of progressive liver failure, intolerance to enteral feeding, and failure to thrive occurs. Isolated liver transplantation removes the contributing effects of liver failure and portal hypertension, allowing time and improved conditions for further bowel adaptation (28). For those children who have underlying motility disorder or abnormal small bowel structure, adaptation is unlikely and combined or sequential liver and small bowel transplantation will be necessary (29). A few reports in the literature describe patients with SBS who have good outcome after isolated liver transplantation (29–31). These reports all differ from this case in that the patients did not ultimately become independent of PN. Lawrence et al. (30) described four infants who underwent isolated liver transplantation for PN-related cholestasis; all survived but remained on PN, and two developed mild cholestasis approximately 12 months after transplant. The patient in the report by Gottrand et al. (31) also did well with isolated liver transplantation in the medium term and showed catch up growth while receiving PN. A patient who received a liver transplant followed by small bowel transplant from separate donors (28) did well initially with no technical complications; however, this child died after overwhelming adenovirus infection, related to the need for high-dose immunosuppression. Children with SBS who have good prognostic features such as intact ileocecal valve, preservation of the colon, and partial tolerance of enteral feeding and who seek treatment early for liver failure may be considered for isolated liver transplantation. We have demonstrated that delayed gut lengthening is feasible after isolated liver transplantation and can result in independence from PN. As far as we know, this is the first reported case of Bianchi longitudinal intestinal lengthening and tailoring procedure performed in a patient with SBS who already had undergone isolated liver transplantation. We emphasis that reversible causes of liver dysfunction should be identified (chronic sepsis of the feeding catheter, cholecystitis, sludge/stones partially obstructing the biliary tree) and treated before recourse to liver transplantation. It is essential that in selecting patients for this unusual sequence of treatments, a detailed assessment from a multidisciplinary team that includes a dietitian, a gastroenterologist, and a hepatologist is made in a dedicated center experienced in the management of liver and small bowel transplantation and bowel reconstructive surgery (5,6). Acknowledgment: The authors thank S. Potts and Dr. McGill for referring the patient to us and thank the members of the Intestinal Failure Group at Birmingham Childrens Hospital, who included Dr. M. S. Murphy, Dr. S. P. Protheroe, Dr. P. John, Prof. I. W. Booth, A. D. Mayer, Mr. Mirza, Mr. Buckels, G. A. Brook, G. Gordon, J. Sira, C. E. Holden, and J. Hunt for their advice on clinical management.