Low circulating concentrations of citrulline and FGF19 predict chronic cholestasis and poor survival in adult patients with chronic intestinal failure: development of a Model for End-Stage Intestinal Failure (MESIF risk score)

Koelfat, K.V.; Huijbers, Angelique; Schaap, Frank G.; Kuijk, Sander M. J. van; Leníček, Martin; Soeters, Maarten R.; Wanten, Geert; Damink, Steven W. M. Olde

doi:10.1093/ajcn/nqz036

Cited by 13 publications

(11 citation statements)

References 40 publications

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“…Six hours after the start of the intravenous meal infusion, plasma C4 levels were still elevated compared to the overnight fasted baseline levels. This suggests that intravenous meal infusion stimulated hepatic bile acid synthesis [45]. Fxr-null mice showed increased hepatic Cyp7a1 gene expression, which reflects dis-inhibited bile acid synthesis [46].…”

Section: Discussionmentioning

confidence: 99%

Parenteral nutrition impairs plasma bile acid and gut hormone responses to mixed meal testing in lean healthy men

et al. 2021

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Background & aims: To investigate the acute effects of intravenous vs enteral meal administration on circulating bile acid and gut hormone responses. Methods: In a randomized crossover design, we compared the effects of duodenal (via a nasoduodenal tube) vs parenteral (intravenous) administration over 180 min of identical mixed meals on circulating bile acid and gut hormone concentrations in eight healthy lean men. We analysed the bile acid and gut hormone responses in two periods: the intraprandial period from time point (T) 0 until T180 during meal administration and the postprandial period from T180 until T360, after discontinuation of meal administration. Results: Intravenous meal administration decreased the intraprandial (AUC (mmol/L*min) duodenal 1469 ± 284 vs intravenous 240 ± 39, p < 0.01) and postprandial bile acid response (985 ± 240 vs 223 ± 5, p < 0.05) and was accompanied by decreased gut hormone responses including glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, glucagon-like peptide 2 and fibroblast growth factor 19. Furthermore, intravenous meal administration elicited greater glucose concentrations, but similar insulin concentrations compared to enteral administration. Conclusions: Compared to enteral administration, parenteral nutrition results in lower postprandial bile acid and gut hormone responses in healthy lean men. This was accompanied by higher glucose concentrations in the face of similar insulin concentrations exposing a clear incretin effect of enteral mixed meal administration. The alterations in bile acid homeostasis were apparent after only one intravenous meal.

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Section: Discussionmentioning

confidence: 99%

Parenteral nutrition impairs plasma bile acid and gut hormone responses to mixed meal testing in lean healthy men

et al. 2021

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“…Although citrulline, which is generated from glutamine by the enterocyte, reflects intestinal absorption capacity in patients with short‐bowel syndrome, altered glutamine metabolism during critical illness affects its accuracy in the intensive care unit (ICU) 17,18 . Recent work from our group has established that the bile salt–induced gut hormone fibroblast growth factor 19 (FGF19) is a prognostic marker in chronic intestinal failure and that the postprandial response of FGF19 to a lipid challenge is blunted in critically ill patients 19,20 . Preclinical studies demonstrated that FGF19 exerts several metabolic actions, including stimulation of hepatic protein synthesis and preservation of the trophic state in skeletal muscle 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Postprandial rise of essential amino acids is impaired during critical illness and unrelated to small‐intestinal function

Gassel

Poll

Schaap

et al. 2021

J Parenter Enteral Nutr

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Background Postprandial rise of plasma essential amino acids (EAAs) determines the anabolic effect of dietary protein. Disturbed gastrointestinal function could impair the anabolic response in critically ill patients. Aim was to investigate the postprandial EAA response in critically ill patients and its relation to small‐intestinal function. Methods Twenty‐one mechanically ventilated patients and 9 healthy controls received a bolus containing 100 ml of a formula feed (Ensure) and 2 g of 3‐O‐Methyl‐d‐glucose (3‐OMG) via postpyloric feeding tube. Fasting and postprandial plasma concentrations of EAAs, 3‐OMG, total bile salts, and the gut‐released hormone fibroblast growth factor 19 (FGF19) were measured over a 4‐hour period. Changes over time and between groups were assessed with linear mixed‐effects analysis. Early (0–60 minutes) and total postprandial responses are summarized as the incremental area under the curve (iAUC). Results At baseline, fasting EAA levels were similar in both groups: 1181 (1055–1276) vs 1150 (1065–1334) μmol·L−1, P = .87. The early postprandial rise in EAA was not apparent in critically ill patients compared with healthy controls (iAUC60, −4858 [−6859 to 2886] vs 5406 [3099–16,853] µmol·L−1·60 minutes; P = .039). Impaired EAA response did not correlate with impaired 3‐OMG response (Spearman ρ 0.32, P = .09). There was a limited increase in total bile salts but no relevant FGF19 response in either group. Conclusion Postprandial rise of EAA is blunted in critically ill patients and unrelated to glucose absorption measured with 3‐OMG. Future studies should aim to delineate governing mechanisms of macronutrient malabsorption.

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“…Others have demonstrated resolution of chronic cholestasis following restoration of intestinal continuity of the small bowel with colon in adult patients with short bowel syndrome, possibly due to a reduction in the amount of PN administered . Disruption of the liver‐gut axis in patients with small bowel resections has also been implicated as one of the possible mechanisms contributing to the development of cholestatic IFALD in both the paediatric and adult IF populations . In the normal situation, bile salts regulate their own synthesis in the liver.…”

Section: Introductionmentioning

confidence: 99%

Review article: diagnosis and management of intestinal failure‐associated liver disease in adults

Bond

Huijbers

Pironi

et al. 2019

Aliment Pharmacol Ther

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Summary Background Hepatic disturbances in the context of intestinal failure and parenteral nutrition (PN) are frequently encountered and carry a significant burden of morbidity and sometimes mortality. The term intestinal failure‐associated liver disease (IFALD) refers to liver injury due to intestinal failure and associated PN, in the absence of another evident cause of liver disease, encompassing a spectrum of conditions from deranged liver enzymes, steatosis/ steatohepatitis, cholestasis as well as progressive fibrosis, cirrhosis and end‐stage liver disease. Aims To present an up to date perspective on the diagnosis/definition, aetiologies and subsequent management of IFALD and to explore future consideration for the condition, including pharmacological therapies Results In adults using long‐term PN for benign chronic intestinal failure, 1%‐4% of all deaths are attributed to IFALD. The aetiology of IFALD is multifactorial and can be broadly divided into nutritional factors (eg lipid emulsion type) and patient‐related factors (eg remaining bowel anatomy). Given its multifaceted aetiology, the management of IFALD requires clinicians to investigate a number of factors simultaneously. Patients with progressive liver disease should be considered for combined liver‐intestine transplantation, although multivisceral grafts have a worse prognosis. However, there is no established non‐invasive method to identify progressive IFALD such that liver biopsy, where appropriate, remains the gold standard. Conclusion A widely accepted definition of IFALD would aid in diagnosis, monitoring and subsequent management. Management can be complex with a number of factors to consider. In the future, dedicated pharmacological interventions may become more prominent in the management of IFALD.

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Low circulating concentrations of citrulline and FGF19 predict chronic cholestasis and poor survival in adult patients with chronic intestinal failure: development of a Model for End-Stage Intestinal Failure (MESIF risk score)

Cited by 13 publications

References 40 publications

Parenteral nutrition impairs plasma bile acid and gut hormone responses to mixed meal testing in lean healthy men

Parenteral nutrition impairs plasma bile acid and gut hormone responses to mixed meal testing in lean healthy men

Postprandial rise of essential amino acids is impaired during critical illness and unrelated to small‐intestinal function

Review article: diagnosis and management of intestinal failure‐associated liver disease in adults

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