Adults (n. 688)
Children (n. 166)
Short bowel syndrome (no. (%))
514 (74.7 %)
87 (52.4 %)
Mesenteric ischemia
36 %
Crohn’s disease
29 %
Rx enteritis
10 %
Surgical complications
8 %
Familial polyposis
4 %
Volvulus
2 %
25 %
Intestinal atresia
23 %
Intestinal malformation
19 %
Necrotizing enterocolitis
15 %
Gastroschisis
6 %
Others
11 %
12 %
Motility disorder
124 (18.0 %)
38 (22.9 %)
CIPO
56 %
71 %
Rx enteritis
16 %
Scleroderma
6 %
MNGIE
3 %
Hirschsprung’s disease
2 %
16 %
Others
17 %
13 %
Extensive parenchymal disease
35 (5.1 %)
41 (24.7 %)
Coeliac
17 %
Atrophy-Ig deficiency
14 %
7 %
Crohn’s disease
14 %
10 %
Lymphangiectasia
11 %
12 %
Rx enteritis
9 %
Tufting enteropathy
6 %
24 %
Autoimmune enteropathy
6 %
7 %
Intractable diarrhea
3 %
17 %
Microvillus atrophy
10 %
Others
20 %
12 %
Intestinal fistulas
15 (2.2 %)
0
Surgical complication
60 %
Crohn’s disease
27 %
Others
13 %
Intestinal rehabilitation programs based on medical treatment and non-transplant surgery can improve the intestinal functions and allow weaned off HPN [4]. Patients with irreversible CIF are destined to lifelong HPN or to intestinal transplantation (ITx). Published cohorts [5] showed mean 5- and 10-year survival rates on HPN of 70 and 55 % in adults and 89 and 81 % in children. HPN complications were the cause of 14 % of deaths in adults and of up to 70 % of deaths in babies <1 year [5]. The 2013 International Transplant Registry report showed a 5-year patient survival rate of 40–60 % in adults and 50–70 % in children, depending on the type of transplant with the best results after isolated small bowel ITx. Almost all the deaths after ITx were related to the treatment [6].
On the basis of data on safety and efficacy, HPN is considered the primary treatment for CIF. The indications for ITx were firstly developed by expert consensus in 2001 and could be categorized as HPN failure, high risk of death due to the underlying disease, or very poor quality of life (QoL) related to the underlying IF [2, 7, 8] (Table 23.2). Those indications were based on retrospective analyses of national and international registries and individual center cohorts of CIF. Subsequently, there have been many advances in the management of CIF resulting in much better outcomes [4, 5, 9]. Therefore, in 2004, the Home Artificial Nutrition and Chronic Intestinal Failure working group of the European Society for Clinical Nutrition (ESPEN) carried out a 5-year prospective comparative study to evaluate their appropriateness [2, 10, 11]. Two cohorts of patients on HPN for CIF were compared: 165 candidates for ITx (108 adults, 57 children, having an indication and no contraindication for ITx) and 418 noncandidates (322 adults, 96 children, having neither an indication nor a contraindication for ITx). The 5-year survival rate on HPN was 87 % in noncandidates, 74 % in candidates with HPN failure, 84 % in those with high-risk underlying disease, and 100 % in those with high-morbidity IF/low acceptance of HPN. The analysis of the risk of death and the causes of death on HPN associated with each indication showed that only patients with liver failure due to intestinal failure-associated liver disease (IFALD) or invasive intra-abdominal desmoids had an actual increased risk of death on HPN. In these patients, almost all (91.7 %) of deaths on HPN were related to an indication for ITx. On the contrary, none of the other indications for ITx showed a statistically significant increased risk of death on HPN, and only 35.8 % of deaths occurred in patients with these indications were related to the underlying disease or to HPN. The European survey suggested a revision of the referral criteria for ITx [5, 11].
Table 23.2
Five-year relative risk of death on home parenteral nutrition (HPN) reported in the European prospective survey [2, 10, 11], for each indication criteria for intestinal transplantation (ITx) as defined by the USA Medicare Services [7] and by the American Society of Transplantation position paper [8]. Proposed revision of the criteria, according to the observed results
Proposed revision of the criteria for patient referral for ITx, according to the results of the European survey | ||||
|---|---|---|---|---|
Indication criteria for ITx | 5-year risk of death on HPN | |||
RR | P | |||
Failure of HPN | ||||
IFALD-related liver failure: Impending (total bilirubin above 3–6 mg/dL/54–108 μmol/L, progressive thrombocytopenia, and progressive splenomegaly) or Overt liver failure (portal hypertension, hepatosplenomegaly, hepatic fibrosis or cirrhosis) | 3.2 | 0.002 | Significantly increased risk of death on HPN. Criterion for a life-saving ITx Comment: Combined liver and intestinal transplantation is a potential life-saving therapy Isolated intestinal transplant may reverse liver fibrosis or cirrhosis in adults with SBS and no signs of portal hypertension and preserved hepatic synthetic function Isolated liver transplant may be successful in children with SBS, liver failure, and portal hypertension, who have favorable prognostic features for full enteral adaptation and weaning from HPN after transplantation | |
CVC-related thrombosis of ≥2 central veins | 2.1 | 0.058 | Nonsignificant increased risk of death on HPN. “Borderline” criterion for a life-saving ITx, requiring a case-by-case decision Comment: Complete or impending loss of venous access has never been reported Venous access is required for the graft procedure; a delay in referral for transplant evaluation until conventional venous access is lost can prove disastrous | |
Frequent and severe CVC-related sepsis: 2 or more episodes per year of systemic sepsis secondary to line infections requiring hospitalization A single episode of line-related fungemia Septic shock and/or acute respiratory distress syndrome | 1.1 | 0.929 | No increased risk of death on HPN. This can be no longer a criterion for referral for ITx Comment: Sepsis is the most frequent cause of death after ITx Proper education and specific training of patients and caregivers is the most important strategy for reducing the risk of CVC-related infections. Taurolidine and ethanol locks are new promising strategies | |
Frequent episodes of severe dehydrations, despite intravenous fluids in addition to HPN | 0 | No increased risk of death on HPN. This can be no longer a criterion for referral for ITx Comment: This indication was based on the risk of chronic renal failure due to recurrent episodes of acute renal failure because of dehydration in patients with high intestinal losses of fluids and electrolytes Decrease of renal function and the risk for developing chronic renal failure are greater after ITx than during HPN | ||
High risk of death attributable to the underlying disease | ||||
Intra-abdominal invasive desmoid tumors | 7.1 | <0.001 | Significantly increased risk of death on HPN. Criterion for a life-saving ITx Comment: In these patients, the need for HPN has been reported to represent a strong predictor of mortality because it mirrors the progression of the tumor | |
Ultra-SBS (gastrostomy, duodenostomy, residual small bowel <10 cm in infants or <20 cm in adults) | 0.8 | 0.763 | No increased risk of death on HPN. This can be no longer a criterion for a straight referral for ITx; a case-by-case decision is required Comment: This indication was based on the higher risk of IFALD-related liver failure and CVC-related sepsis in patients with an ultra-SBS, reported by earlier case series Recent improvements in intestinal rehabilitation programs have significantly decreased this risk | |
Congenital mucosal disorders (e.g., microvillus atrophy, intestinal epithelial dysplasia) | 0.4 | 0.374 | No increased risk of death on HPN. This can be no longer a criterion for a straight referral for ITx; a case-by-case decision is required Comment: Earlier case series reported uniformly poor outcomes associated with these mucosal enteropathies. Recent surveys showed improved outcomes, with some children successfully weaned off HPN to full oral nutrition | |
Very poor quality of life (IF with high morbidity or low acceptance of HPN) | ||||
Need for frequent hospitalization, narcotic dependency, or inability to function Patient’s unwillingness to accept long-term home parenteral nutrition | No increased risk of death on HPN. This could be a potential criterion for a “rehabilitative ITx” in case-by-case carefully selected patients Comment: A recent comparative study clearly indicated that a successful ITx can improve the quality of life of patients with CIF destined to lifelong HPN | |||
23.2 Proposed Revision of the Indications for ITx, According to the Results of the European Survey [2, 5, 10, 11] (Table 23.2)
Liver failure due to IFALD showed a statistically significant increased risk of death on HPN and was confirmed as a referral criterion for a life-saving ITx. Abnormalities of liver function tests (LFTs) have been reported at a frequency of between 15 and 85 % of patients on HPN [12, 13]. Chronic cholestasis with inflammation and rapid progression to fibrosis, portal hypertension, and end-stage liver disease is the predominant histologic feature in neonates and infants <6 months, whereas steatosis and steatohepatitis with a slower evolution to fibrosis are the principal lesions in older children and adults [14]. In 22 adult case series and 16 children cohorts, IFALD-related death represented the 4–5 % and the 16–60 % of total death on HPN, respectively, with a mortality rate greater in premature infants and in babies [5].
The pathogenesis of IFALD is multifactorial [5, 12, 13]. Total oral fasting and very short bowel syndrome (SBS) are the main IF-related factors. The main HPN-related factors consist of excess total energy, excess glucose, or excess soybean-based lipid emulsions (LE) (>1 g/Kg body weight/day in adults and >2.5 g/Kg/day in children), rich in proinflammatory omega-6 polyunsaturated fatty acids, even without hyperalimentation [30, 31]. Other potential HPN factors may be excess phytosterols in LE and antioxidant deficiency, like vitamin E. A key role has been demonstrated for the systemic or intra-abdominal inflammation, notably through sepsis – of whatever origin – or intestinal bacterial translocation [5, 12–16].
In the recent years, prevention and treatment of IFALD have improved allowing to avoid the need for ITx in a consistent number of patients [4]. The main strategies aim to maintain oral feeding, to decrease the risk of central venous catheter (CVC)-related sepsis, and to decrease the amount of soybean-based LE, or its replacement with fish oil-based LE, containing the anti-inflammatory omega-3 polyunsaturated fatty acids as well as higher amount of vitamin E and lower concentration of phytosterols, would be recommended [16, 18].
When medical treatment fails, the issues of patient referral for transplantation, type of transplantation, and timing of transplantation arise. According to a severity classification of IFALD proposed in 2008 [19], persistent hyperbilirubinemia from 3 to 6 mg/dL (50–100 μmol/L) would be a criterion for referral to intestinal failure rehabilitation unit and persistent concentration >6 g/dL a criterion for consultation or referral for transplantation assessment and listing. Knowing when hepatic fibrosis is progressing up to irreversible cirrhosis is a key issue for the timing for referral as well as for the type of transplantation. LFTs do not predict the degree of histological injury [14]. A recent study [17] in adults found that the FibroScan® score, a noninvasive marker of liver fibrosis in various liver diseases, was significantly correlated with the histological score of cholestasis but not of fibrosis. Therefore, serial liver biopsy remains the gold standard for assessing IFALD.
Related posts:
Infection Complications After Abdominal Organ Transplantation
The Intraoperative and Perioperative Management of Kidney Transplantation
Anesthetic and Perioperative Management for Intestinal Transplantation
Retransplantation (Causes, Outcome)
Percutaneous Treatment of Biliary and Vascular Complications
Intestinal/Multivisceral Transplantation
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