Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome

Meehan, John J.; Georgeson, Keith E.

doi:10.1016/s0022-3468(97)90609-6

Cited by 81 publications

(61 citation statements)

References 10 publications

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“…3 The etiology of the liver disease in these patients has not been clearly established, but is likely multifactorial. 3,[7][8][9][10] Several factors that correlate with its occurrence include duration of TPN therapy, 9 length of residual small bowel, 3 and the presence of residual colon. 3 Other factors that are implicated include bacterial overgrowth, 8 composition of TPN macronutrients (i.e., lipids, carbohydrates), 3 missing nutritional factors, 7 and hepatotoxic factors in TPN.…”

Section: Discussionmentioning

confidence: 99%

Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants

Fryer

Pellar

Ormond³

et al. 2003

Liver Transplantation

141

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The United Network for Organ Sharing (UNOS) reports indicate that mortality on the intestine transplant waiting list is higher than on other transplant waiting lists. The goals of this study were (1) to determine whether most of the intestinal transplant candidate deaths have occurred in those who also need liver transplants, and (2) to compare the waiting list mortality in the liver-intestine candidate subset with the overall liver transplant candidate population. We found that 90% of intestine transplant waiting list deaths have occurred in candidates who also needed liver transplants. Since 1994, annual mortality has been higher in liver-intestine transplant candidates than in the overall liver transplant candidate population, and these differences have been statistically significant since 1996. These mortality differences applied to all age groups. Also, status 2B, 3, and 7 candidate mortality was significantly higher in liver-intestine candidates than in the overall liver transplant candidate population. Because there were so few liver-intestine transplant candidates listed as status 1 or 2A, a meaningful comparison was not possible in these statuses. These data indicate that liverintestine transplant candidates are a unique subset of liver transplant candidates with a significantly higher risk of dying on the waiting list. Recent changes in UNOS liver allocation policy that gives higher priority to liver-intestine candidates may help to reduce this discrepancy. However, further research into the etiology of liver disease in patients on long-term parenteral nutrition and earlier referral of high-risk short bowel syndrome patients to centers with special expertise in their management are needed for an ultimate solution to this problem. (Liver Transpl 2003;9:748-753.)

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Section: Discussionmentioning

confidence: 99%

Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants

Fryer

Pellar

Ormond³

et al. 2003

Liver Transplantation

141

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“…Unfortunately, there are adverse consequences associated with TPN maintenance such as intestinal atrophy, electrolyte and metabolic alterations, increased intestinal permeability, sepsis, and cholestasis (6,48,51,53). In the pediatric population, TPN cholestasis and secondary liver dysfunction are major causes of morbidity and mortality (4,32,42,53); thus the development of a therapeutic strategy that could enhance the intestinal adaptive response and reduce the requirements for TPN would be invaluable.…”

mentioning

confidence: 99%

Glucagon-like peptide-2 induces intestinal adaptation in parenterally fed rats with short bowel syndrome

Martin¹,

Wallace²,

Sigalet³

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

135

121

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Glucagon-like peptide-2 (GLP-2) is an intestinal trophic enteroendocrine peptide that is associated with intestinal adaptation following resection. Herein, we investigate the effects of GLP-2 in a total parenteral nutrition (TPN)-supported model of experimental short bowel syndrome. Juvenile Sprague-Dawley rats underwent a 90% small intestinal resection and jugular catheter insertion. Rats were randomized to three groups: enteral diet and intravenous saline infusion, TPN only, or TPN + 10 μg·kg−1·h−1 GLP-2. Nutritional maintenance was isocaloric and isonitrogenous. After 7 days, intestinal permeability was assessed by quantifying the urinary recovery of gavaged carbohydrate probes. The following day, animals were euthanized, and intestinal tissue was processed for morphological and crypt cell proliferation (CCP) analysis, apoptosis (caspase-3), and expression of SGLT-1 and GLUT-5 transport proteins. TPN plus GLP-2 treatment resulted in increased bowel and body weight, villus height, intestinal mucosal surface area, CCP, and reduced intestinal permeability compared with the TPN alone animals ( P < 0.05). GLP-2 treatment induced increases in serum GLP-2 levels and intestinal SGLT-1 expression ( P < 0.01) compared with either TPN or enteral groups. No differences were seen in the villus apoptotic index between resection groups. Enterally fed resected animals had a significant decrease in crypt apoptotic indexes compared with nontreated animals. This study demonstrates that GLP-2 alone, without enteral feeding, stimulates indexes of intestinal adaptation. Secondly, villus hypertrophy associated with adaptation was predominantly due to an increase in CCP and not to changes in apoptotic rates. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2.

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“…This is especially challenging in the pediatric population, where it is relatively common, and supportive therapy is frequently complicated by the development of total parenteral nutrition (TPN) induced cholestasis (1)(2)(3). At present, treatment in human infants is primarily supportive while the process of intestinal adaptation, or up-regulation of nutrient absorption capacity, occurs (2,3). The description of the intestinal trophic effects of Glucagon Like Peptide 2 (GLP-2) has renewed optimism that we may be able to modify or accelerate this process of adaptation (4 -6).…”

mentioning

confidence: 99%

GLP-2 Levels in Infants With Intestinal Dysfunction

et al. 2004

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Glucagon Like Peptide 2 (GLP-2) has been proposed as an important regulatory hormone in nutrient absorption. The present study was conducted in human infants with intestinal dysfunction undergoing surgery, correlating postprandial GLP-2 levels with intestinal length, nutrient absorption, and patient outcome. We hypothesized that GLP-2 levels would be inversely related to nutrient absorption; we further hypothesized that post prandial GLP-2 levels would be predictive of the ability to wean patients from total parenteral nutrition (TPN), and tolerance of enteral feeding. Infants prospectively identified with nutrient malabsorption following intestinal surgery were monitored and after initiation of feeds GLP-2 levels were measured in the fed state. Intestinal length was recorded intraoperatively and nutrient absorption was quantified using both a balance study, and carbohydrate probe method. 12 infants had GLP-2 levels successfully measured; two patients had repeated studies. Average gestational age was 32.7 Ϯ 3.4 wk, age at testing was 1.7 Ϯ 1.4 mo and average weight was 3.5 Ϯ 1.1 kg. Causes of intestinal loss were necrotizing enterocolitis, atresia and volvulus. Five patients had severe short bowel syndrome (Ͻ50% of normal small intestinal length), 3 died. GLP-2 levels were best correlated with residual small intestinal length (r 2 ϭ 0.75). Correlations with total intestinal length including colon were less significant; residual colon appeared to not contribute to measurable GLP-2 production. GLP-2 levels were well correlated with tolerance of enteral feeds. Contradicting the initial hypothesis, GLP-2 levels were directly correlated with nutrient absorptive capacity (correlation with fat absorption: r 2 ϭ 0.72, carbohydrate ϭ 0.50 and protein ϭ 0.54 respectively). There were no apparent changes in GLP-2 levels with gestational or postnatal age. As a corollary to the correlation with bowel length, a postprandial level of 15 pmol/L appeared to be discriminatory; infants with postprandial GLP-2 levels of Ͼ 15 pmol/L were able to be weaned from total parenteral nutrition, while 3 of 4 infants who had GLP-2 levels less than 15 could not be weaned by one year. These results show that in infants with intestinal dysfunction, GLP-2 levels are correlated with residual small bowel length and nutrient absorption, and may be predictive of outcome. In contrast to adults with intact colon and SBS, infants with SBS and intact colon do not appear able to produce GLP-2 in response to feeding stimulation. Nutrient malabsorption due to inadequate intestinal surface area, or short bowel syndrome (SBS) is a difficult clinical problem. This is especially challenging in the pediatric population, where it is relatively common, and supportive therapy is frequently complicated by the development of total parenteral nutrition (TPN) induced cholestasis (1-3). At present, treatment in human infants is primarily supportive while the process of intestinal adaptation, or up-regulation of nutrient absorption capacity, occurs (2,3). The descriptio...

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Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome

Cited by 81 publications

References 10 publications

Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants

Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants

Glucagon-like peptide-2 induces intestinal adaptation in parenterally fed rats with short bowel syndrome

GLP-2 Levels in Infants With Intestinal Dysfunction

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