Chronic cholestasis in patients on parenteral nutrition: the influence of restoring bowel continuity after mesenteric infarction

Adaba, Franklin; Uppara, Mallikarjuna; Iqbal, Fareed; Mallappa, Sreelakshmi; Vaizey, C. J.; Gabe, S.M.; Warusavitarne, Janindra; Nightingale, Julie

doi:10.1038/ejcn.2015.147

Cited by 13 publications

(6 citation statements)

References 23 publications

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“…Of note, it has been shown that phytosterols, major constituents of soybean oil, promote cholestatic liver disease, highlighting the need to minimize use of soybean oil-based lipid emulsions to prevent cholestatic liver injury (24,25). Although liver failure due to IFALD remains the main indication for intestine or combined liver-intestine transplantation, more recent studies showed declines in the prevalence of chronic cholestatic liver injury (20-30%) relative to the 50% prevalence reported in an initial study in 2000 (5,8,9). In the large cohort studied here, we found a slightly lower prevalence of 17%.…”

Section: Discussionmentioning

confidence: 99%

“…Between 24% and 65% of CIF patients develop liver injury (e.g., steatosis, cholestasis, or fibrosis), collectively known as intestinal failure-associated liver disease (IFALD) (5)(6)(7)(8)(9). Ultimately, IFALD may progress to liver failure, which is accompanied by higher rates of referral for intestinal or multivisceral transplantation (ITx) and home parenteral nutrition (HPN)-related mortality (10).…”

Section: Introductionmentioning

confidence: 99%

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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)

Koelfat

Huijbers

Schaap

et al. 2019

The American Journal of Clinical Nutrition

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Background: Patients with chronic intestinal failure (CIF) often develop cholestatic liver injury, which may lead to liver failure and need for organ transplantation. Objectives: The aim of this study was to investigate whether citrulline (CIT) and the enterokine fibroblast growth factor 19 (FGF19) are associated with chronic cholestasis and survival in adult CIF patients, and to develop a risk score to predict their survival. Methods: We studied 135 adult CIF patients on intravenous supplementation (>3 mo). Associations of plasma CIT and FGF19 with chronic cholestasis and survival were estimated by logistic and Cox regression models. A predictive risk score was developed and validated internally. Results: Patients with chronic cholestasis (17%) had a reduced 5y survival rate compared with patients without chronic cholestasis (38% and 62%, respectively). In multivariable analysis, low FGF19, low CIT, and female sex were associated with chronic cholestasis. Patients with low rather than high CIT or FGF19 also had reduced 5y survival rates (29% compared with 69%; 54% compared with 66%, respectively). Risk factors identified in multivariable analysis of survival were low FGF19 (HR: 3.4), low CIT (HR: 3.3), and number of intravenous infusions per week (HR: 1.4). These 3 predictors were incorporated in a risk model of survival termed Model for End-Stage Intestinal Failure (MESIF) (C-statistic 0.78). The 5-y survival rates for patients with MESIF scores of 0 to <20 (n = 47), 20-40 (n = 75), and >40 (n = 13) were 80%, 58%, and 14%, respectively. Conclusions: CIT and FGF19 predict chronic cholestasis and survival in this cohort of adult CIF patients, and the derived MESIF score is associated with their survival. Pending external validation, the MESIF score may help to identify patients for closer clinical monitoring or earlier referral to intestinal transplantation centers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Huijbers

Schaap

et al. 2019

The American Journal of Clinical Nutrition

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“…Thus, surgical strategies that restore gastro‐intestinal continuity should be considered at an early stage of a patient's CIF care pathway. Adaba et al demonstrated that eight of 15 (53%) home PN‐dependent adults with chronic cholestasis had a return of LFTs to the normal range within one year of restoration of bowel continuity . Where restoration of continuity cannot be achieved, intestinal lengthening procedures offer a viable alternative to both adults and children .…”

Section: Managementmentioning

confidence: 99%

“…Adaba et al demonstrated that eight of 15 (53%) home PN-dependent adults with chronic cholestasis had a return of LFTs to the normal range within one year of restoration of bowel continuity. 66 Where restoration of continuity cannot be achieved, intestinal lengthening procedures offer a viable alternative to both adults 95 and children. [96][97][98] Yannam et alreported successful outcomes in 20 adult patients with CIF undergoing intestinal lengthening with a 90% survival rate and 10 patients achieving complete weaning of PN with restoration of enteral autonomy.…”

Section: Absorptive Capacitymentioning

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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“…The early restoration of intestinal passage is more advantageous than intestinal ostomy. In the case of active nutritional support to a patient with a stoma, parenteral nutrition increases the risk of cholestasis and liver failure; only restoration of the enteral digestion leads to restoration of liver function [10]. In patients with an ultrashort small intestine remaining after emergency resection, restoration of the intestinal passage by imposing an anastomosis between the jejunum and the colon reduces the risk of recurrent ischemic damage and leads to the cancellation of parenteral nutrition in 35-50% of cases within a year [11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Surgical Technique on the Microstructure and Microcirculation of the Small Intestine Stump during Delayed Anastomosis: Multimodal OCT Data

Kiseleva¹,

Ryabkov

Sizov

et al. 2021

Sovrem Tehnol Med

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The aim of the study was to use multimodal optical coherence tomography (MM OCT) to evaluate microstructure and microcirculation in the proximal and distal sections of the intestine relative to the resected area in acute mesenteric ischemia.Materials and Methods. The study was carried out using three groups of male Wistar rats weighing 270-435 g (n=18). Acute occlusive arterial ischemia of the small intestine was initiated in all animals. After 80-90 min, the ischemic non-viable part of the intestine was resected, and the operation was completed by stoma exteriorization (group 1, n=6), by applying purse-string sutures (group 2, obstructive resection, n=6), or by internal drainage of the proximal and distal ends of the small intestine (group 3, bypass, n=6). Relaparotomy and anastomosis formation were performed 2 days later.With the help of MM OCT at each stage of the surgical intervention, images were obtained from the serous membrane side: the intestinal wall microstructure (layers) was viewed using cross-polarization OCT (CP OCT) and the intramural circulation -using optical coherent angiography (OCA). The MM OCT images obtained from the terminal intestine sections immediately after resection and 2 days later (before the anastomosis formation) were compared between the experimental groups, as well as with the pre-ischemic data (norm). All resected sections of the intestine were then histologically examined. The MM OCT data were compared with the histological and intravital macroscopy data.Results. As a result of studying the intestinal wall microstructure by in vivo CP OCT, it was found that during ostomy (group 1) and obstructive resection (group 2), the images showed signs of tissue edema and destructive changes in the mucous membrane that were confirmed histologically, while with bypass surgery (group 3), there were minimal changes as compared with the norm.According to the OCA data, on day 2 of ostomy in the proximal and distal segments of the intestine, there was a noticeable disappearance of small and medium blood vessels; mainly large arteries and veins could be visualized. Following obstructive resection (purse-string suturing) or bypass surgery, the most noticeable changes (a decrease in the number of visualized blood vessels) were observed in the distal part of the intestine. The L index calculated from OCA images and characterizing the total length of the intramural perfused vasculature, showed a statistically significant decrease during ostomy: 12.18 [10.40; 14.20] µm -in the proximal and 10.67 [7.98; 13.05] µm -in the distal section; for comparison, the L index before ischemia was 18. 90 [17.98; 19.73] μm and 18.74 [17.46; 19.90] μm, respectively (p=0.0001). In obstructive resection (group 2), statistically significant differences in the L parameter were found only for the distal bowel section: 16.39 [12.37; 18.10] µm compared with 18.74 [17.46; 19.90] μm before ischemia (p=0.041). After bypass surgery (group 3), there were no significant deviations in the L index.Conclusion. By using MM OCT, we ...

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Chronic cholestasis in patients on parenteral nutrition: the influence of restoring bowel continuity after mesenteric infarction

Abstract: The prevalence of CC is 29% for patients with a short bowel receiving PN following a mesenteric infarction. CC resolves in 53% after continuity is restored, and this is most likely due to stopping or reducing the PN.

Cited by 13 publications

References 23 publications

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)

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)

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

Effect of Surgical Technique on the Microstructure and Microcirculation of the Small Intestine Stump during Delayed Anastomosis: Multimodal OCT Data

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