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1.
Long‐Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure–Associated Liver Disease
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Prathima Nandivada MD Gillian L. Fell MD PhD Paul D. Mitchell MSc Alexis K. Potemkin BSN RN Alison A. O'Loughlin MEd Kathleen M. Gura PharmD Mark Puder MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2017,41(6):930-937
Background: Fish oil lipid emulsion (FOLE) and multidisciplinary care for infants with intestinal failure (IF) have been associated with reduced morbidity and mortality due to IF‐associated liver disease (IFALD). With increased survival, a greater proportion of infants with IF are now able to remain on parenteral nutrition (PN) in the long term. The purpose of this study was to examine outcomes in children with IFALD who have required long‐term PN and FOLE therapy due to chronic IF. Materials and Methods: A review of prospectively collected data was performed for children with IFALD who required at least 3 years of PN and FOLE therapy due to chronic IF. Outcomes examined include the incidence of death, transplantation, and essential fatty acid deficiency (EFAD), as well as growth parameters and the biochemical markers of liver disease. Results: Of 215 patients with IFALD treated from 2004–2015, 30 required PN and FOLE therapy for at least 3 years (median, 4.6 years). To date, no patients have died, required transplantation, or developed EFAD. Biochemical markers of liver disease normalized within the first year of therapy with no recurrent elevations in the long term. Weight‐for age and length‐for‐age z scores improved and PN dependence decreased in the first year of therapy, with a stable rate of growth in the long term. Conclusions: Children with IFALD who required long‐term PN and FOLE for chronic IF had no mortality, need for transplantation, EFAD, or recurrence of liver disease in the long term, allowing for continued intestinal rehabilitation. 相似文献
2.
Diamond IR de Silva NT Tomlinson GA Pencharz PB Feldman BM Moore AM Ling SC Wales PW 《JPEN. Journal of parenteral and enteral nutrition》2011,35(5):596-602
Background: Given the recent interest in the role of ω‐6 lipids in the development of intestinal failure–associated liver disease (IFALD), the authors sought to examine the role of parenteral lipids in the development of a serum conjugated bilirubin >100 µmol/L (5.9 mg/dL; CB100) in infants. Method: Between 2003 and 2004, data were collected prospectively on infants undergoing an abdominal surgical procedure. Univariate logistic regression models for the prediction of CB100 by 1 year postoperatively were developed. Predictors significant at the 0.2 level on univariate analysis were entered into a backward stepwise multiple variable logistic regression. Results: Of 152 infants who received parenteral nutrition (PN) postoperatively, 22 developed CB100. Predictors that met criteria for consideration in the multiple‐variable model were age, weight, small bowel length, presence of a stoma, proportion of enteral feeds postoperatively, septic episodes, days of maximal PN amino acid (>2.5 g/kg/d), days of maximal lipid (>2.5 g/kg/d), and PN duration. The final model included septic episodes (odds ratio, 3.23; 95% confidence interval, 1.8–5.9) and days of lipid >2.5 g/kg/d (1.04; 1.003–1.06). At 60 days of maximal lipid, the odds of advanced IFALD were increased 10‐fold. Conclusions: This model suggests a key role of parenteral lipids and septic events in the development of CB100 from IFALD. These data may provide targets, such as careful line care, reduction in maximal lipid dose, or alternate lipids such as ω‐3 fatty acids, to prevent CB100, an identified marker of subsequent liver failure from IFALD. 相似文献
3.
Parenteral Soybean Oil Induces Hepatosteatosis Despite Addition of Fish Oil in a Mouse Model of Intestinal Failure–Associated Liver Disease
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Prathima Nandivada MD Gillian L. Fell MD PhD Amy H. Pan BSc Vania Nose MD Paul D. Mitchell MSc Kathleen M. Gura PharmD Mark Puder MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2018,42(2):403-411
4.
Prevalence,Evolution, and Risk Factors for Advanced Liver Fibrosis in Adults Undergoing Intestinal Transplantation
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Geneviève Huard MD MPH CHUM M. Isabel Fiel MD Jang Moon MD Kishore Iyer MD Thomas D. Schiano MD 《JPEN. Journal of parenteral and enteral nutrition》2018,42(7):1195-1202
Introduction
Intestinal failure–associated liver disease (IFALD) occurs commonly in intestinal transplant (ITx) candidates receiving parenteral nutrition (PN). The aim of this study is to establish the prevalence and risk factors for advanced liver fibrosis in adults at the time of ITx.Methods
Retrospective chart review of all ITx was performed in adults between January 2000 and May 2014. Advanced liver fibrosis was defined as stage 3 or stage 4 fibrosis.Results
Fifty‐three patients met the inclusion criteria. The mean age was 50.6 ± 10.9 years, and the majority were female (60.4%) and Caucasian (67.9%). The mean body mass index was 21.7 ± 3.8 kg/m2 and the median duration of PN was 402 (interquartile range: 529) days. Advanced liver fibrosis at the time of ITx was found in 13 patients (24.5%). The multivariate analysis revealed that female gender and white race were significant predictors of advanced liver fibrosis. A total bilirubin >3.0 mg/dL for > a month prior to ITx was associated with an odds ratio of 8.9 for advanced fibrosis at the time of ITx but did not reach statistical significance (P = 0.055).Conclusion
Close to one‐quarter of the ITx recipients had advanced liver fibrosis. In the current era of improved PN management, our data suggests that previously reported risk factors for IFALD, such as extreme short gut syndrome and PN duration, may have a lesser impact on development of liver fibrosis. A prolonged duration of bilirubin elevation may be associated with advanced liver fibrosis in patients with IFALD, but this requires validation in a larger cohort. 相似文献5.
Giuseppe Lauriti MD PhD Augusto Zani MD PhD Roberto Aufieri MD Mara Cananzi MD PhD Pierluigi Lelli Chiesa MD Simon Eaton BSc PhD Agostino Pierro MD FRCS FRCS FAAP 《JPEN. Journal of parenteral and enteral nutrition》2014,38(1):70-85
Background: Cholestasis is a significant life‐threatening complication in children on parenteral nutrition (PN). Strategies to prevent/treat PN‐associated cholestasis (PNAC) and intestinal failure–associated liver disease (IFALD) have reached moderate success with little supporting evidence. Aims of this systematic review were (1) to determine the incidence of PNAC/IFALD in children receiving PN for ≥14 days and (2) to review the efficacy of measures to prevent/treat PNAC/IFALD. Methods: Of 4696 abstracts screened, 406 relevant articles were reviewed, and studies on children with PN ≥14 days and cholestasis (conjugated bilirubin ≥ 2 mg/dL) were included. Analyzed parameters were (1) PNAC/IFALD incidence by decade and by PN length and (2) PNAC/IFALD prevention and treatment (prospective studies). Results: Twenty‐three articles (3280 patients) showed an incidence of 28.2% and 49.8% of PNAC and IFALD, respectively, with no evident alteration over the last decades. The incidence of PNAC was directly proportional to the length of PN (from 15.7% for PN ≤1 month up to 60.9% for PN ≥2 months; P < .0001). Ten studies on PNAC met inclusion criteria. High or intermediate‐dose of oral erythromycin and aminoacid‐free PN with enteral whey protein gained significant benefits in preterm neonates (P < .05, P = .003, and P < .001, respectively). None of the studies reviewed met inclusion criteria for treatment. Conclusions: The incidence of PNAC/IFALD in children has no obvious decrease over time. PNAC is directly correlated to the length of PN. Erythromycin and aminoacid‐free PN with enteral whey protein have shown to prevent PNAC in preterm neonates. There is a lack of high‐quality prospective studies, especially on IFALD. 相似文献
6.
Intravenous Fish Oil and Pediatric Intestinal Failure–Associated Liver Disease: Changes in Plasma Phytosterols,Cytokines, and Bile Acids and Erythrocyte Fatty Acids
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Kara L. Calkins MD MS Andrea DeBarber PhD Robert D. Steiner MD Martiniano J. Flores MS Tristan R. Grogan MS Susanne M. Henning RN PhD Laurie Reyen RN MN Robert S. Venick MD 《JPEN. Journal of parenteral and enteral nutrition》2018,42(3):633-641
Background: Soybean oil (SO) emulsions are associated with intestinal failure–associated liver disease (IFALD); fish oil (FO) emulsions are used to treat IFALD. SO and FO differ with respect to their fatty acid and phytosterol content. In children with IFALD whose SO was replaced with FO, we aimed to (1) quantify changes in erythrocyte fatty acids and plasma phytosterols, cytokines, and bile acids and (2) correlate these changes with direct bilirubin (DB). Design: This study enrolled IFALD children who received 6 months of FO. Blood samples were collected prior to FO, and after 2 weeks and 3 and 6 months of FO. The primary outcome was 3‐month vs baseline biomarker concentrations. Results: At study initiation, the median patient age was 3 months (interquartile range, 3–17 months), and mean ± standard deviation DB was 5.6 ± 0.7 mg/dL (n = 14). Cholestasis reversed in 79% of subjects. Eicosapentaenoic and docosahexaenoic acid was greater than baseline (P < .001, all time points). Linoleic and arachidonic acid and sitosterol and stigmasterol were less than baseline (P < .05, all time points). Three‐ and 6‐month interleukin‐8 (IL‐8) and total and conjugated bile acids were less than baseline (P < .05). Baseline IL‐8 was correlated with baseline DB (r = 0.71, P < .01). Early changes in stigmasterol and IL‐8 were correlated with later DB changes (r = 0.68 and 0.75, P < .05). Conclusion: Specific fat emulsion components may play a role in IFALD. Stigmasterol and IL‐8 may predict FO treatment response. 相似文献
7.
Xinhua Zhu MD Yafu Wu BS Yudong Qiu MD Chunping Jiang BS Yitao Ding MS 《JPEN. Journal of parenteral and enteral nutrition》2013,37(1):68-74
Background: The effect of parenteral nutrition (PN) support supplemented with ω‐3 fatty acids was investigated in a randomized, controlled clinical trial at the Affiliated Drum Tower Hospital, Medical School of Nanjing University. Materials and Methods: Ninety‐eight patients with the diagnosis of end‐stage liver disease or hepatic cellular carcinoma were admitted for orthotopic liver transplantation at the Affiliated Drum Tower Hospital. The patients were randomly divided into 3 groups: diet group (n = 32), PN group (n = 33), and polyunsaturated fatty acid (PUFA) group (n = 33). Patients in the PN and PUFA groups received isocaloric and isonitrogenous PN for 7 days after surgery. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery. A pathological test was performed after reperfusion of the donor liver and on day 9. Results: Alanine aminotransferase levels were improved significantly by PUFA treatment compared with traditional PN support (P < .05). Compared with the results on day 9 in the PN group, a significant difference was seen in the extent of increase of the prognostic nutrition index and prealbumin in the PUFA group. The pathological results also showed that ω‐3 fatty acid supplementation reduced hepatic cell injury. PUFA therapy also decreased the incidence of infectious morbidities and shortened the posttransplant hospital stay significantly. Conclusion: Posttransplant PN support can greatly improve metabolism of protein and nutrition states of patients. ω‐3 fatty acid–supplemented PN significantly reduces injury of the transplanted liver, decreases the incidence of infectious morbidities, and shortens posttransplant hospital stay. 相似文献
8.
Alexandra N. Carey Coral Rudie Paul D. Mitchell Bram P. Raphael Kathleen M. Gura Mark Puder 《JPEN. Journal of parenteral and enteral nutrition》2019,43(2):305-310
Infants requiring prolonged parenteral nutrition (PN) may receive intravenous (IV) lipid in the form of soybean oil, fish oil, or a composite lipid emulsion (CLE) (i.e., SMOFlipid®). Soybean oil lipid‐dose restriction is a popular method of treating and reducing the risk of intestinal failure–associated liver disease (IFALD) that may influence dosing strategies of other IV fat emulsions. Here we present 4 infants receiving PN with SMOFlipid® as their IV lipid source and examine trends in essential fatty‐acid status, triglycerides, and dosing strategy. The infants on restricted doses of CLE developed biochemical essential fatty‐acid deficiency (EFAD) that resolved with a dosage increase or by transition to a pure fish‐oil lipid emulsion. Three of the 4 infants originally prescribed CLE were diagnosed with IFALD and started a pure fish‐oil lipid emulsion after treatable causes of cholestasis were excluded. One of the 4 infants presented with hypertriglyceridemia that resolved upon transition to pure fish‐oil lipid emulsion. Misapplication of lipid restriction protocols to CLE regimens render infants at risk for EFAD. CLE should be dosed within recommended ranges to prevent EFAD. Restricted protocols warrant close monitoring of essential fatty‐acid status in infants receiving prolonged PN, particularly in those with minimal or no enteral intake. Hypertriglyceridemia and cholestasis are known adverse effects of CLE and require monitoring. 相似文献
9.
Makay O Kaya T Firat O Sozbilen M Caliskan C Gezer G Uyar M Ersin S 《JPEN. Journal of parenteral and enteral nutrition》2011,35(4):488-492
Background: Preoperative and intraoperative nutrition support in patients undergoing major surgery results in decreased incidence of morbidity and mortality. Studies investigating the role of ω‐3 fatty acids in these patients are increasing. Some are focused on perfusion at the cellular level. This study was undertaken to address the effect of postoperative administration of ω‐3 fatty acids on cellular hypoperfusion associated with major gastric surgery. Methods: Twenty‐six patients undergoing gastric cancer surgery were randomly assigned to receive parenteral nutrition (PN) supplemented with a combination of ω‐6 and ω‐3 fatty acids (Omegaven, 0.2 g/kg/d; Lipovenoes 10%, 0.6 g/kg/d) or with ω‐6 fatty acid (Lipovenoes 10%, 0.8 g/kg/d) for 5 days. Blood samples were taken preoperatively, postoperative day 1, and on the last day of PN therapy (day 5). Results: Patients receiving ω‐3 and ω‐6 fatty acids showed neither lower serum lactate levels nor lower rates of complications compared with patients receiving ω‐6 only. There were no statistically significant differences between the groups in other biochemical parameters, complications, or length of hospital stay or mortality. Conclusion: PN with ω‐3 fatty acid supplementation does not have a significant impact on cellular hypoperfusion and lactate clearance after major gastric surgery. 相似文献
10.
Preventing the Progression of Intestinal Failure–Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid
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Ivan R. Diamond MD Robert C. Grant MD Paul B. Pencharz MD Nicole de Silva RN Brian M. Feldman MD Peter Fitzgerald MD David Sigalet MD Bryan Dicken MD Justine Turner MD Valerie Marchand MD Simon C. Ling MD Aideen M. Moore MD Yaron Avitzur MD Paul W. Wales MD 《JPEN. Journal of parenteral and enteral nutrition》2017,41(5):866-877
Background: To examine whether SMOFlipid prevents progression of intestinal failure–associated liver disease (IFALD) in parenteral nutrition (PN)–dependent infants with early IFALD (conjugated bilirubin 17–50 µmol/L, 1‐3 mg/dL). Study Design: Pilot multicenter blinded randomized controlled trial comparing SMOFlipid with Intralipid. Patients received the trial lipid for up to 12 weeks, unless they achieved full enteral tolerance sooner. The primary clinical outcome was the serum conjugated bilirubin. Results: Twenty‐four infants (mean age, 6 weeks) participated in the trial (13 Intralipid and 11 SMOFlipid). At the time of trial enrollment, patients in both groups were receiving 90% of their calories by PN. Mean duration on trial was 8 weeks and did not differ according to treatment (P = .99). At trial conclusion, patients who received SMOFlipid had a lower conjugated bilirubin than those who received Intralipid (mean difference, –59 µmol/L; P = .03). Patients receiving SMOFlipid were also more likely to have a decrease in serum conjugated bilirubin to 0 µmol/L than those in the Intralipid group over the entire observation period (hazard ratio, 10.6; 95%; P = .03). The time to achievement of full enteral tolerance did not differ statistically (hazard ratio, 1.3; P = .59) between the groups. There was no significant difference in safety outcomes between the groups. Conclusions: Compared with Intralipid, SMOFlipid reduces the risk of progressive IFALD in children with intestinal failure. This trial was registered at clinicaltrials.gov as NCT00793195. 相似文献
11.
Single‐Center Experience with the Use of Teduglutide in Adult Patients with Short Bowel Syndrome
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Kwai Lam RD CNSC CDN Lauren Schwartz MD Jennifer Batisti MD Kishore R. Iyer MBBS FRCS FACS 《JPEN. Journal of parenteral and enteral nutrition》2018,42(1):225-230
Background
Teduglutide is a glucagon‐like peptide 2 (GLP‐2) analog that has been approved for the treatment of adult short bowel syndrome (SBS)–associated intestinal failure (IF; SBS‐IF). Teduglutide increases villus height and crypt depth in the small bowel mucosa, promoting nutrition absorption and enteral independence from parenteral nutrition (PN). We aim to report our single‐center experience with teduglutide in adult patients with SBS to provide real‐world context to its use.Method
We conducted a retrospective analysis on patients managed within our tertiary‐level intestinal rehabilitation program to identify patients with SBS‐IF treated with teduglutide from 2009–2015. The current report includes all patients at our center who had any exposure to teduglutide, including those who received commercial drug after approval by the Food and Drug Administration (FDA) and outside the scope of clinical trials.Results
A total of 18 patients were treated with teduglutide. Eleven patients (61%) achieved complete enteral independence from PN and/or intravenous fluids (IV) at a median time of 10 months (range: 3–36 months). PN/IV volume requirement was reduced in all patients except two. Ten of the 11 patients (91%) who achieved enteral autonomy had colon. All patients off PN/IV required additional oral vitamins and electrolyte supplementations.Conclusion
Our preliminary experience is consistent with prior reports of successful partial or complete weaning from PN/IV with teduglutide treatment in adult patients with SBS. The presence of colon appears to be favorable in obtaining enteral independence from PN/IV, regardless of residual small bowel length. Patients on teduglutide may remain at high risk of micronutrient deficiencies. 相似文献12.
Kara L. Calkins MD James C. Y. Dunn MD PhD Stephen B. Shew MD Laurie Reyen RN MN Douglas G. Farmer MD Sherin U. Devaskar MD Robert S. Venick MD 《JPEN. Journal of parenteral and enteral nutrition》2014,38(6):682-692
Background: Studies have suggested that when intravenous (IV) soybean oil (SO) is replaced with fish oil (FO), direct hyperbilirubinemia is more likely to resolve. The necessary duration of FO has not been established. This study seeks to determine if 24 weeks of FO is an effective and safe therapy for intestinal failure–associated liver disease (IFALD). Materials and Methods: This is a clinical trial using patients with IFALD between the ages of 2 weeks and 18 years. SO was replaced with FO (1 g/kg/d) in 10 patients who were receiving most of their calories from parenteral nutrition (PN). Patients were compared with 20 historic controls receiving SO. SO for both groups was prescribed by the primary medical team at variable doses. The primary outcome was time to reversal of cholestasis. Secondary outcomes were death, transplant, and full enteral feeds. Safety measurements included growth, essential fatty acid deficiency, and laboratory markers to assess bleeding risk. Results: The Kaplan‐Meier method estimated that 75% in the FO group would experience resolution of cholestasis by 17 weeks vs 6% in the SO group (P < .0001). When compared with the SO group, the FO group had decreased serum direct bilirubin concentrations at weeks 8 (P = .03) and 12, 16, 20, and 24 weeks (P < .0001). Although length z score at the end of the study increased in the FO group compared with baseline (P = .03), there were no significant differences in other outcomes. Conclusions: A limited duration of FO appears to be safe and effective in reversing IFALD. 相似文献
13.
Manpreet S. Mundi MD Aravind R. Kuchkuntla MBBS Bradley R. Salonen MD Sara Bonnes MD Ryan T. Hurt MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2020,44(2):301-307
Background: Although home parenteral nutrition (HPN) is lifesaving for patients with chronic intestinal failure (IF), long-term use can be associated with complications such as infections, metabolic abnormalities, and IF–associated liver disease (IFALD). The key to treatment of many of these complications is prevention. Guidelines recommend avoidance of overfeeding, use of oral/enteral nutrition if possible, cyclic PN, and maintaining dose of soybean oil (SO) intravenous lipid emulsion (ILE) <1 g/kg/day as preventive strategies for IFALD. Additionally, with development of IFALD, ω-6/ω-3 polyunsaturated fatty acid ratio should be decreased in ILE. The newly available mixed-oil (MO) ILE offers such an opportunity; however, there is a paucity of long-term data available. Methods: The current study reports our long-term experience with MO ILE use in HPN patients. Results: Seventeen patients (8 female and 9 male) with an average age of 47 ± 12 years and median HPN duration of 4.6 years (1.1–32.1 years) have utilized MO ILE for >12 months after being transitioned from SO ILE because of intolerance. Use of MO ILE allowed an increase in ILE energy from 8% ± 8% to 22% ± 8% while reducing dextrose energy from 66% ± 8% to 54% ± 5%, maintaining stability in alkaline phosphatase and triglyceride levels, and achieving improvement in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and α-tocopherol levels. Conclusion: In this HPN cohort with SO ILE intolerance, MO ILE was well tolerated and allowed an improvement in macronutrient composition while improving some liver parameters over a 12-month period. 相似文献
14.
Parenteral Nutrition Utilization After Implementation of Multidisciplinary Nutrition Support Team Oversight
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Brodie Parent MD Marilyn Shelton RD Megan Nordlund RD Shahram Aarabi MD MPH Grant O'Keefe MD MPH 《JPEN. Journal of parenteral and enteral nutrition》2016,40(8):1151-1157
Background: Multidisciplinary nutrition teams can help guide the use of parenteral nutrition (PN), thereby reducing infectious risk, morbidity, and associated costs. Starting in 2007 at Harborview Medical Center, weekly multidisciplinary meetings were established to review all patients receiving PN. This study reports on observed changes in utilization from 2005–2010. Materials and Methods: All patients who received PN from 2005–2010 were followed prospectively. Clinical data and PN utilization data were recorded. Patients were grouped into cohorts based on exposure to weekly multidisciplinary nutrition team meetings (from 2005–2007 and from 2008–2010). Patients were also stratified by location, primary service, and ultimate disposition. Results: In total, 794 patients were included. After initiation of multidisciplinary nutrition meetings, the rate of patients who started PN decreased by 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.63–0.84). A reduction in the number of patients receiving PN was observed in both the intensive care unit (ICU) and on the acute care floor (RR, 0.64; 95% CI, 0.53–0.77 and RR, 0.80; 95% CI, 0.64–0.99, respectively). The rate of patients with short‐duration PN use (PN duration of <5 days) declined by 30% in the ICU (RR, 0.70; 95% CI, 0.51–0.97) and by 27% on acute care floors (RR, 0.73; 95% CI, 0.51–1.03). Conclusions: Weekly multidisciplinary review of patients receiving PN was associated with reductions in the number of patients started on PN, total days that patients received PN, and number of patients who had short‐duration (<5 days) PN use. 相似文献
15.
Justine M. Turner MD PhD Jessica Josephson MSc Catherine J. Field PhD Pamela R. Wizzard BSc Ronald O. Ball PhD Paul B. Pencharz MD PhD Paul W. Wales MD MSc 《JPEN. Journal of parenteral and enteral nutrition》2016,40(7):973-981
Background: The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure–associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω‐6 and ω‐3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil–based emulsion (ω‐6:ω‐3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium‐chain triglycerides, 25% olive oil, and 15% fish oil (ω‐6:ω‐3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Method: Neonatal piglets, 3–6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C‐reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Results: Compared with the IL group, ML‐treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω‐6 long‐chain PUFA content was lower in plasma and brain for the ML group. The key ω‐3 long‐chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. Conclusion: The mixed lipid, having less ω‐6 PUFA and more ω‐3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN‐fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes. 相似文献
16.
Surgical Anatomy Does Not Affect the Progression of Intestinal Failure–Associated Liver Disease in Neonatal Piglets
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Celeste M. Lavallee BSc RD Pamela R. Wizzard BSc RAHT Marihan Lansing MBBCh Donna F. Vine PhD Patrick N. Nation PhD Jason Y. Yap BHB MBChB FRACP Benjamin P. Willing PhD Paul W. Wales MD FRCSC MSc Justine M. Turner MBBS FRACP PhD 《JPEN. Journal of parenteral and enteral nutrition》2018,42(1):14-23
Background: Intestinal failure–associated liver disease (IFALD) causes significant morbidity in neonates with short bowel syndrome (SBS) dependent on parenteral nutrition (PN). Resected ileum, with loss of the ileocecal valve (ICV), is the most common anatomy in SBS, yet its impact on IFALD has not been adequately studied. Methods: Neonatal piglets were randomized to 75% intestinal resection with jejunocolic anastomosis (JC, n = 12), 75% resection with jejunoileal anastomosis and intact ICV (JI, n = 13), PN‐fed sham (sham, n = 14), or sow‐fed control (SF, n = 8). Surgical and sham piglets received 100% PN for 14 days before bile flow was measured and blood chemistry, liver pathology, jejunal permeability, and bacterial translocation were assessed. Results: Bile flow was lower for PN‐fed compared with SF (P = .002) but not different between the PN‐fed groups. Total bilirubin (P = .03) and liver pathology (P < .001) were greater in PN‐fed than SF groups but not different between PN‐fed groups. Serum bile acids were increased in sham (P = .01) but not different between SBS groups. PN‐fed piglets with sepsis had lower bile flow (P = .001) and increased bilirubin (P = .04). Neither jejunal permeability nor bacterial translocation were different between JC, JI, or sham groups. Conclusion: Contrary to our hypothesis, the remnant anatomy does not appear to worsen the progression of IFALD. However, the role of sepsis in IFALD should be further explored, in addition to other mechanisms, including PN factors, host immune responses, and intestinal bacterial dysbiosis. 相似文献
17.
Ivan R. Diamond MD PhD Robert C. Grant MA Brian M. Feldman MD MSc George A. Tomlinson PhD Paul B. Pencharz MBChB PhD Simon C. Ling MBChB Aideen M. Moore MD Paul W. Wales MD MSc 《JPEN. Journal of parenteral and enteral nutrition》2014,38(6):702-710
Objective: To determine expert beliefs regarding the probability of intestinal failure–associated liver disease (IFALD) with novel lipid‐based approaches (lipid minimization/ω‐3 lipids) in managing IFALD to facilitate Bayesian analyses of clinical trials of these therapies. Study Design: Structured interviews were conducted using a validated approach to belief elicitation with 60 intestinal failure (IF) experts from across North America. Participants were asked to estimate, in an average population of infants referred for management of IF with early IFALD, the probability of advanced IFALD at 3 months following referral in each of 3 scenarios: (1) conventional lipid, (2) ω‐3 lipids, and (3) lipid minimization. Probability distributions of the risk of advanced IFALD with each strategy were developed. Distributions of the elicited treatment effect for the novel approaches, relative to conventional lipid, were calculated. Results: Median duration of experience of participants managing patients with IF was 8.5 (range, 2–35) years. The median probability of advanced IFALD using conventional lipid was 32.5%; ω‐3 lipids, 17.5%; and lipid minimization, 13%. The median of the elicited treatment effects relative to conventional lipid was a relative risk of 0.53 for the ω‐3 lipid and 0.45 for lipid minimization. Conclusions: There was consistent expert opinion that the novel lipid‐based approaches are superior to conventional therapy, with similar estimates of treatment efficacy for the 2 approaches. The distributions of the elicited treatment effects can be used as prior distributions in Bayesian analyses of clinical trials of these novel strategies. 相似文献
18.
Esther Prince MD Farrah B. Lazare DO William R. Treem MD Jiliu Xu MD Jahangir Iqbal PhD Xiaoyue Pan PhD Joby Josekutty PhD Meghan Walsh BA Virginia Anderson MD M. Mahmood Hussain PhD Steven M. Schwarz MD 《JPEN. Journal of parenteral and enteral nutrition》2014,38(5):608-616
Objectives: ω‐3 Fatty acids (FAs), natural ligands for the peroxisome proliferator‐activated receptor–α (PPAR‐α), attenuate parenteral nutrition–associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω‐3 FAs are still unknown. The aim of this study was to determine the effects of ω‐3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR‐α and microsomal triglyceride transfer protein (MTP) in this experimental setting. Methods: 129S1/SvImJ wild‐type or 129S4/SvJaePparatm/Gonz/J PPAR‐α knockout mice were fed chow and water (controls); oral, fat‐free PN solution only (PN‐O); PN‐O plus intraperitoneal (IP) ω‐6 FA‐predominant supplements (PN–ω‐6); or PN‐O plus IP ω‐3 FA (PN–ω‐3). Control and PN‐O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR‐α messenger RNA were assessed after 19 days. Results: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN‐O and PN–ω‐6 groups accumulated significantly greater amounts of TG when compared with PN–ω‐3 mice. Studies in PPAR‐α null animals showed that PN feeding increases hepatic TG as in wild‐type mice. PPAR‐α null mice in the PN‐O and PN–ω‐6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω‐3 FAs. Conclusions: PN induces TG accumulation (steatosis) in wild‐type and PPAR‐α null mice. In PN‐fed wild‐type and PPAR‐α null mice given IP ω‐3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω‐3 FAs results from PPAR‐α–independent pathways. 相似文献
19.
Choline Protects Against Intestinal Failure–Associated Liver Disease in Parenteral Nutrition–Fed Immature Rats
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Jie Zhu MD PhD Ting Lu BSc Fei Chen BSc Junkai Yan MS Fan Chen BSc Qiaosen Zhang BSc Jifan Wang BSc Weihui Yan MD PhD Tingxi Yu MD PhD Qingya Tang MD Wei Cai MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2018,42(2):436-445
Background: Deficiency of choline, a required nutrient, is related to intestinal failure–associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms. Methods: Male Sprague‐Dawley rats (4 weeks old) were fed AIN‐93G chow and administered intravenous 0.9% saline (control), parenteral nutrition (PN), or PN plus intravenous choline (600 mg/kg) for 7 days. We evaluated body weight, hepatic histology, biochemical indicators, triglycerides, oxidative status, methylation levels of peroxisomal proliferator‐activated receptor alpha (PPARα) gene promoter, expression of PPARα and carnitine palmitoyltransferase 1 (CPT1), and levels of choline metabolites. Results: The PN + choline group exhibited improved body weight compared with the PN group. PN impaired hepatic function, increased hepatic triglycerides, induced dyslipidemia, enhanced reactive oxygen species and malondialdehyde, and reduced total antioxidant capacity. The PN group had higher pathologic scores than the control group. These results were prevented by choline administration. Compared with the control group, PN increased PPARα promoter methylation and hepatic betaine concentration, reduced hepatic choline and phosphatidylcholine (PC) levels, decreased plasma choline and betaine concentrations, and downregulated PPARα and CPT1 mRNA and protein expression. Choline supplementation elevated hepatic choline and PC levels and enhanced plasma choline, betaine, and PC concentrations but reduced hepatic betaine level, reversed PPARα promoter hypermethylation, and upregulated PPARα and CPT1 mRNA and protein expression in PN‐fed rats, compared with rats receiving PN alone. Conclusion: Choline addition to PN may prevent IFALD by reducing oxidative stress, enhancing hepatic fat export, and promoting fatty acid catabolism in immature rats receiving PN. 相似文献
20.
C. Puiggròs MD J. Sánchez MD P. Chacón MD P. Sabín PhD J. Roselló MD R. Bou PhD M. Planas MD 《JPEN. Journal of parenteral and enteral nutrition》2009,33(5):501-512
Background: The metabolic effects of intravenous lipid emulsions (ILEs) used in parenteral nutrition (PN) depend on their fatty acid composition. Methods: Subjects in this prospective and randomized double‐blind study were 28 adult patients post digestive surgery. PN was started after surgery and lasts for 5 days. Randomly, patients receive 1 of 4 different ILEs: medium‐chain triglycerides/long‐chain triglycerides (soybean oil; MCT/LCT), olive/soybean oil (oleic), long‐chain triglycerides (soybean oil; LCT), and structured lipid. On days 0 and 6, serum liver function tests were analyzed for cholesterol, triglycerides, lipoproteins, and serum fatty acids. Results: No differences were found in the 4 groups according to their gender, age, body mass index, diagnosis, baseline white blood cell, C‐reactive protein, glucose levels, and other study parameters. Differential significant changes were not observed in any of the hepatic function parameters or plasmatic lipid levels between the groups. A significant decrease was observed in cis monounsaturated fatty acids (MUFAs) and a significant increase in ω‐6 polyunsaturated fatty acids (PUFAs) andω ‐3 PUFA values in LCT and structured groups compared with MCT/LCT and oleic groups, and a tendency for a decrease in trans fatty acids in the oleic and structured groups was found. Conclusions: All ILEs administered were safe and well tolerated. The changes in serum fatty acids reflected the pattern of fatty acids administered with different ILEs. The group receiving the olive oil emulsion achieved a fatty acid composition of serum lipids that could offer major therapeutic or biological advantages. 相似文献