Intestinal Failure-associated Liver Disease Research Articles

Lipid absorption and overall intestinal lymphatic transport are impaired following partial small bowel resection in mice

Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal lipid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling may account at least in part for impaired intestinal uptake and transport of fat via the compromised lymphatic architecture. We believe that these changes may contribute to the development of intestinal failure associated liver disease (IFALD), a major morbidity in patients with SBS.

Infection Prevention and Management in Pediatric Short Bowel Syndrome.

Short bowel syndrome (SBS) is a rare disease with potentially life-threatening consequences. In addition to intestinal failure-associated liver disease, infections and other complications related to central venous catheters (CVCs) cause a significant burden to patients with SBS and may even necessitate an intestinal transplant eventually. The need for long-term central venous access and the intestinal dysfunction associated with SBS drive the need for intestinal failure-specific approach to prevent and treat infections in patients with SBS. In bacterial infections, the line can often be salvaged with proficient antibiotic therapy. Repeated catheter replacements are predisposed to recurrent infections and thrombotic complications, which may limit the long-term survival of patients with SBS. Protocol-based CVC access procedures and daily care including taurolidine and ethanol catheter locks have been shown to reduce infection rates substantially. Compromised intestinal function in SBS predisposes to small bowel bacterial overgrowth, mucosal injury, and increased permeability. These pathophysiological changes are concentrated in a subset of patients with excessive bowel dilatation and frequent bowel-derived infections. In such patients, reconstructive intestinal surgery may be indicated. Probiotics have not been effective in infection prevention in SBS and carry a significant risk of complications. While more studies focusing on the prevention of infections and their complications are needed, protocol-based approach and multidisciplinary teams in the care of patients with SBS have been shown to reduce complications and improve outcomes.

Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome.

Short bowel syndrome (SBS) is a major cause of intestinal failure (IF) that may require long-term parenteral nutrition (PN) support. However, long-term PN is accompanied by severe complications such as catheter-related blood stream infection (CRBSI) and intestinal failure-associated liver disease (IFALD), and it is associated with high healthcare costs. In this study, we characterized the plasma metabolomic profile and investigated the role of metabolism in predicting long-term PN in pediatric patients with SBS. Untargeted metabolomics was performed in plasma samples from 20 SBS patients with PN support: 6 patients had IFALD and 14 patients had no liver disease. As controls, 18 subjects without liver or intestinal diseases were included for the analysis. SBS patients had distinct plasma metabolomic signatures compared to controls, and several pathways associated with amino acid metabolism and cell death were significantly changed. The presence of IFALD in SBS was associated with alterations of metabolites mainly classified as “amino acids, peptides, and analogues” and “benzene and derivatives”. Serum direct bilirubin levels were negatively correlated with levels of uridine, skatole, and glabrol. Importantly, SBS patients with long-term PN showed significantly increased levels of glutamine compared to those in the short-term PN group. Finally, using multivariate logistic regression analysis, we developed a prediction model including glutamine and creatinine to identify pediatric SBS patients who need long-term PN support. These findings underscore the potential key role of the metabolome in SBS with IF and suggest that metabolomic profiles could be used in long-term PN assessment.

50 Years Ago in TheJournalofPediatrics: How Sweet It Is: Hyperglycemia in Infants on Parenteral Nutrition

Driscoll JM, Heird WC, Schullinger JN, Gongaware RD, Winters RW. Total intravenous alimentation in low-birth-weight infants: a preliminary report. J Pediatr 1972;81:145-53. In 1972, Dr Driscoll reported the outcomes of 9 very low birth weight infants receiving parenteral nutrition (PN). Full nutrition was provided with glucose, aminosol, electrolytes, and vitamins infused at a constant rate. The glucose content was gradually increased based on blood and urine glucose levels. Compared with conventionally managed infants, this group met or exceeded expected weight gain and were quicker to regain birth weight. These early results were encouraging; PN could provide adequate nutrition in this high-risk group. Metabolic derangements were the most frequent complication, with recurrent hyperglycemia occurring in 5 patients. Two infants had dehydration from osmotic diuresis and 2 required insulin. Fifty years later, hyperglycemia is a known complication of PN and is associated with significant morbidity and mortality.1Sinclair J.C. Bottino M. Cowett R.M. Interventions for prevention of neonatal hyperglycemia in very low birth weight infants.Cochrane Database Syst Rev. 2011; 5 (Available from:): CD007453https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007615.pub3/fullGoogle Scholar Monitoring of blood glucose levels and ramping infusion rates to prevent hyper or hypoglycemia are now routine practice. In 2011, guidelines from the American Society of Parenteral and Enteral Nutrition were published recommending a serum glucose goal of less than 150 mg/dL in neonates.2Arsenault D. Brenn M. Kim S. Gura K. Compher C. Simpser E. et al.A.S.P.E.N. clinical guidelines: hyperglycemia and hypoglycemia in the neonate receiving parenteral nutrition.J Parenter Enter Nutr. 2012; 36: 81-95Crossref PubMed Scopus (35) Google Scholar Fat emulsions, which were not approved for children until 1981, were also recommended to allow for reduction in glucose infusions rate from increased gluconeogenesis. There are ongoing advancements in our ability to detect hyperglycemia. A study of very low birth weight infants demonstrated improved glycemic control using a continuous glucose monitor to adjust glucose infusions rate compared with standard of care glucometer.3Galderisi A. Facchinetti A. Steil G.M. Ortiz-Rubio P. Cavallin F. Tamborlane W.v. et al.Continuous Glucose Monitoring in Very Preterm Infants: A Randomized Controlled Trial [Internet].http://publications.aap.org/pediatrics/article-pdf/140/4/e20171162/1097183/peds_20171162.pdfGoogle Scholar Lipids are now a key component of modern PN, and the use of omega-3 fish oil-based formulations have helped mitigate the risk of intestinal failure-associated liver disease.4Khalaf R.T. Sokol R.J. New insights into intestinal failure-associated liver disease in children.Hepatology. 2020; 71: 1486-1498Crossref PubMed Scopus (27) Google Scholar The urgency of supporting premature infants with complete nutrition is as relevant now as it was 50 years ago. Balancing the morbidity of prematurity with the risks of medical therapy continues to be a priority in the care of these patients.

Histopathological liver steatosis linked with high parenteral glucose and amino acid supply in infants with short bowel syndrome.

Steatosis is a common feature of intestinal failure-associated liver disease (IFALD) in adult and older pediatric patients receiving long-term parenteral nutrition (PN). There are limited clinical data concerning steatosis in infants with short bowel syndrome (SBS). We investigated early histopathological steatosis and its association to PN. In this retrospective study, 31 patients with SBS had a diagnostic liver biopsy taken at the median age of 5 (IQR 3-8) months. Follow-up biopsy was available for 24 patients at the median age of 29 (IQR 14-52) months. We evaluated the biopsies for steatosis and other histopathological signs of IFALD and compared results with patient characteristics, PN composition, and liver biochemistry. Diagnostic biopsies revealed steatosis in 8 (26%) patients. At the age of 3 months, patients with steatosis had received higher amounts of parenteral glucose: median 15.1 (IQR 12.4-17.2) vs 12.3 (8.7-14.4) g/kg/d (P = 0.04), amino acids: 2.9 (2.5-3.4) vs 2.2 (1.6-2.7) g/kg/d (P = 0.03), and energy: 87 (80-98) vs 73 (54-79) kcal/kg/d (P = 0.01) than those without steatosis. We detected no significant differences in parenteral lipid intake between the groups. Steatosis also associated with increased serum bile acid (P = 0.02), alanine aminotransferase (P = 0.0002), and aspartate aminotransferase (P = 0.001) levels. In this cohort, high parenteral glucose, amino acid, and energy provision associated with liver steatosis in infants with SBS. We recommend monitoring of bile acid and transaminase levels while aiming for PN with balanced macronutrient supply according to current recommendations to protect the liver from steatosis.

Current practices in lipid emulsion utilization in the prevention and treatment of intestinal failure-associated liver disease: A survey of pediatric intestinal rehabilitation and transplant centers.

Newer intravenous lipid emulsions (ILEs), such as fish oil-based intravenous lipid emulsions (FO-ILEs) and soybean oil, medium-chain triglycerides, olive oil, and fish oil-based intravenous lipid emulsions (SMOF-ILEs), provide alternatives to soybean oil-based intravenous lipid emulsions (SO-ILEs). We explored current ILE practice patterns among intestinal rehabilitation and transplant centers. A survey was developed addressing ILE availability, ILE preference in clinical scenarios, and factors influencing ILE choice. This survey was reviewed locally and by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Intestinal Rehabilitation Special Interest Group, the Intestinal Rehabilitation and Transplant Association scientific committee, and the American Society of Parenteral and Enteral Nutrition pediatric intestinal failure section research committee. We recruited providers nationally and internationally from centers with and without intestinal transplant programs. We included 34 complete responses, 29 from the United States. Sixteen centers performed intestinal transplants. All centers had access to SMOF-ILEs, 85% had access to FO-ILEs, and 91% had access to SO-ILEs. In new patients, 85% use SMOF-ILEs as the first choice ILE. In those with new intestinal failure-associated liver disease (IFALD), FO-ILE was preferred to SMOF-ILE (56% vs 38%). In those developing IFALD on SMOF-ILE, 65% switched to FO-ILE, whereas 24% remained on SMOF-ILE. Centers have routine access to alternative ILEs, and these are quickly replacing SO-ILEs in all circumstances. Future work should focus on how this shift in practice affects outcomes to provide decision support in specific clinical scenarios.

Outcomes of the First 54 Pediatric Patients on Long-Term Home Parenteral Nutrition from a Single Brazilian Center.

Objectives:Data on multidisciplinary programs dedicated to home parenteral nutrition (HPN) in Latin America are limited. This study describes the results of the first multidisciplinary pediatric intestinal rehabilitation program for HPN at a public tertiary hospital in Brazil.Methods:We retrospectively reviewed patients aged 0–18 years with intestinal failure (IF) who required parenteral nutrition (PN) for >60 days between January/2014 and December/2020.Results:Fifty-four patients were discharged on HPN (15 achieved enteral autonomy, 34 continued on HPN at the end of the study, 1 underwent intestinal transplantation, and 4 died). The median (IQR) age at the study endpoint of patients who achieved enteral autonomy was 14.1 (9.7–19) versus 34.7 (20.4–53.9) months in those who did not achieve enteral autonomy. Overall prevalence of catheter-related thrombosis was 66.7% and catheter-related bloodstream infection rate was 0.39/1000 catheter-days. Intestinal failure-associated liver disease (IFALD) was present in 24% of all patients; none of the patients who achieved enteral autonomy had IFALD. All patients showed significant improvement in anthropometric parameters during the HPN period. The sociodemographic characteristics of the patients’ family members were mothers less than 20 years old (7.5%), schooling time more than 10 years (55.5%), and household income between 1 and 3 times the minimum wage (64.8%). The 5-year survival rate for HPN is 90%, and 27.7% of patients achieve enteral autonomy.Conclusion:The treatment of pediatric patients with IF followed by a multidisciplinary pediatric intestinal rehabilitation program with HPN is feasible and safe in the Brazilian public health system.

Intestinal Continuity Alleviates Pediatric Intestinal Failure-Associated Liver Disease.

BackgroundType I short bowel syndrome (SBS) occurs after a critical reduction in the functional gut mass and resection of intestinal continuity after ileostomy or jejunostomy for necrotizing enterocolitis (NEC), intestinal atresia or other causes. SBS is often accompanied with intestinal failure-associated liver disease (IFALD) who requires long-term parenteral nutrition (PN). Our study aimed to observe the effect of intestinal continuity on the hepatic function of pediatric intestinal failure (IF) patients with type I SBS.MethodsThe pre-and post-anastomosis medical records of 35 pediatric patients with type I SBS from April 2013 to April 2019 were reviewed retrospectively. The average growth (cm/month) in the proximal and distal small bowel lengths was calculated as the growth in intestinal length (cm)/the duration (month) from enterostomy to anastomosis. The changes in hepatic function from enterostomy to anastomosis were evaluated by assessment of hepatic function before anastomosis for 6 weeks and after anastomosis for 4 weeks.ResultsThe average growth in proximal intestinal length was 9.3 cm/month (±7.2) in neonates and 2.8 cm/month (1.3, 11.9) in infants and children, and in distal intestinal length was 1.5 cm/month (0, 2.7) in neonates and 0.4 cm/month (0, 1.4) in infants and children. The incidence of IFALD was 28.6% 1 month before anastomosis and 20.0% 1 month after anastomosis (p < 0.05).ConclusionIn pediatric type I SBS with IFALD, restoration of intestinal continuity may alleviate liver injury. There was an intestinal compensatory effect on the growth in the intestinal length after resection, and better results were seen in neonates in terms of intestinal length growth.

Bridging Liver Transplantation in the Treatment of Intestinal Failure Associated Liver Disease in Infants-A Bridge Too Far?

Infants with intestinal failure associated liver disease (IFALD) requiring liver and bowel transplant have a high mortality on the transplant waiting list due to the scarcity of the size-matched donor organs. Bridging liver transplantation has been used to allow the children to grow to a reasonable size so that a combined liver and small bowel transplant could be performed in the future. We report on two children with irreversible intestinal failure (ultra-short bowel syndrome secondary to gastroschisis and microvillous inclusion disease) with IFALD who underwent bridging liver transplantation at our institution. Both patients made a good recovery from their initial surgery. One patient died 6 months following surgery from generalized sepsis, and the other patient survived in good condition to undergo a combined liver and small bowel transplant but died a few days post-transplant. In the current era of scarcity of donor organs, this raises an ethical dilemma for the team involved regarding appropriate utilisation of a scarce resource.

The Effects of Different Parenteral Nutrition Lipid Formulations on Clinical and Laboratory Endpoints in Patients Receiving Home Parenteral Nutrition: A Systematic Review

Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes.1 Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life2 but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood.

Investigation and follow up of patients under “hospital A” receiving home parenteral nutrition with liver function test (LFT) derangement

Investigations to help identify the cause of abnormal routine serum LFTs (Alkaline phosphatase (ALP), Alanine Transferase (ALT) and Bilirubin) may be sub-optimal in patients on home parenteral nutrition (HPN), despite the risk of patients developing intestinal failure associated liver disease.1 Suboptimal investigation and follow-up of patients may lead to a delay in multivisceral transplant referral and be associated with adverse outcomes.

The preventive effect of recombinant human hepatocyte growth factor for hepatic steatosis in a rat model of short bowel syndrome

PurposeShort bowel syndrome (SBS) patients require total parenteral nutrition (TPN) following massive small bowel resection (SBR), which may cause intestinal failure-associated liver disease (IFALD), a life-threatening complication. Hepatocyte growth factor (HGF) acts as a potent hepatocyte mitogen with anti inflammatory and antioxidant actions. The present study evaluated the effect of recombinant human HGF (rh-HGF) on SBR and subsequent IFALD using a parentally fed rat model of SBS. MethodsRats underwent jugular vein catheterization for continuous TPN and 90% SBR. They were divided into 2 groups: TPN alone (SBS/TPN group: n = 7) or TPN plus the intravenous administration of rh-HGF (0.3 mg/kg/day) (SBS/TPN+HGF group: n = 7). On day 7, their tissues and stool were harvested to evaluate the effects of HGF. ResultsRegarding the histological findings, based on the nonalcoholic fatty liver disease (NAFLD) activity score, the SBS/TPN+HGF group showed significantly less hepatic steatosis and inflammatory cell infiltration than the SBS/TPN group (NAFLD activity score, 4.00 ± 1.83 vs. 1.00 ± 0.82; p < 0.01). The SBS/TPN+HGF group showed a higher expression of Farnesoid X receptor in the liver and lower expression of Toll-like receptor 4 in the ileum than the SBS/TPN group. Regarding the composition of the bacterial gut microbiota, Actinobacteria, Bacteroidetes and Proteobacteria were decreased in the SBS/TPN+HGF group compared with the SBS/TPN group. ConclusionIn our SBS with TPN rat model, rh-HGF administration had a preventive effect against hepatic steatosis and dysbiosis. rh-HGF may therefore be a potentially effective therapeutic agent for SBS and subsequent IFALD. Type of studyExperimental research.

An analysis of neonatal mortality following gastro-intestinal and/or abdominal surgery in a tertiary hospital in South Africa.

Thirty-day, 6-month and 12-month post-operative mortality and assessment of factors associated with 30day post-operative mortality were ascertained. A retrospective medical record audit for neonates who underwent gastrointestinal or abdominal wall surgery within the neonatal period at a tertiary free standing paediatric hospital during the 12-year period from 1 January 2007 to 31 December 2018. The 30-day post-operative mortality rate was 83/762 (11%). Mortality resulted from: sepsis (74%), palliation due to ultra-short bowel length (12%), ventilation-associated pneumonia (10%), associated congenital cardiac lesions (3%) and intestinal failure-associated liver disease (1%). Surgery for necrotizing enterocolitis had the greatest 30-day post-operative mortality (28%). Most neonates (69%) who died were prematurely born. Mean age at surgery was ten days and mean age at death was six days. Abdominal compartment syndrome was noted post operatively in 15% patients. Risk factors for sepsis included central line-associated bloodstream infections (65%), respiratory tract infections (41%) and surgical complications [anastomotic breakdown (7%) and wound infection (24%)]. Mortality in patients from referral hospitals more than an hour's drive away was high (15/39, 38%). Mortality is double that of high-income countries, although significantly lower than most African settings. Strategic quality-improvement interventions are required to optimize outcomes.

Outcome and management in neonates with gastroschisis in the third millennium—a single-centre observational study

Gastroschisis is one of the most common congenital malformations in paediatric surgery. However, there is no consensus regarding the optimal management. The aims of this study were to investigate the management and outcome and to identify predictors of outcome in gastroschisis. A retrospective observational study of neonates with gastroschisis born between 1999 and 2020 was undertaken. Data was extracted from the medical records and Cox regression analysis was used to identify predictors of outcome measured by length of hospital stay (LOS) and duration of parenteral nutrition (PN). In total, 114 patients were included. Caesarean section was performed in 105 (92.1%) at a median gestational age (GA) of 36 weeks (range 29–38) whereof (46) 43.8% were urgent. Primary closure was achieved in 82% of the neonates. Overall survival was 98.2%. One of the deaths was caused by abdominal compartment syndrome and one patient with intestinal failure–associated liver disease died from sepsis. None of the deceased patients was born after 2005. Median time on mechanical ventilation was 22 h. Low GA, staged closure, intestinal atresia, and sepsis were independent predictors of longer LOS and duration on PN. In addition, male sex was an independent predictor of longer LOS.Conclusion: Management of gastroschisis according to our protocol was successful with a high survival rate, no deaths in neonates born after 2005, and favourable results in LOS, duration on PN, and time on mechanical ventilation compared to other reports. Multicentre registry with long-term follow-up is required to establish the best management of gastroschisis.What is Known:• Gastroschisis is one of the most common congenital malformations in paediatric surgery with increasing incidence.• There is no consensus among clinicians regarding the optimal management of gastroschisis.What is New:• Although primary closure was achieved in 82% of the patients, mortality rate was very low (1.8%) with no deaths in neonates born after 2005 following the introduction of measurement of intraabdominal pressure at closure.• Low gestational age, staged closure, intestinal atresia, sepsis, and male sex were independent predictors of longer length of hospital stay.

Exploring the long-term risk factors associated with intestinal failure-associated liver disease in pediatric and adult patients: The role of lipid injectable emulsions in the development of liver disease.

Despite parenteral nutrition (PN) being life sustaining, one of the risk factors associated with its long-term use is intestinal failure-associated liver disease (IFALD), which increases the risk for morbidity and mortality. This review examines some of the risk factors associated with IFALD. A literature review using the databases PubMed, EMBASE, and CINAHL between 2010 and 2020 was performed using search terms, including long-term total PN and liver failure, serum plant sterols and liver failure, and complications and PN. Articles in English using both human and animal participants were included. The pathophysiology associated with PN and liver disease is multifactorial and influenced by the remaining small-bowel length, presence of the ileal cecal valve, lack of enteral stimulation, type of lipid injectable emulsion (ILE), plant sterol content, and excessive calories. The type of ILE plays a major role because of the phytosterol (PS) content, affecting the microbiome composition and inhibiting key gut signals. The PS content is highest in soy oil (SO)-based ILE, which increases inflammation and impairs biliary flow. Serum PS correlates with liver biomarker abnormalities and is highest in SO-based ILE use compared with mixed-oil emulsions. Selection of a low-PS content ILE is recommended to reduce the risk of biliary cholestasis. Stimulation of the gut, if possible, is recommended to maintain gut integrity and reduce bacterial overgrowth. Fish oil (FO) shows promise in IFALD reversal however, large randomized controlled trials are needed to further establish support for the use of FO in adults.

Beyond lipids: Novel mechanisms for parenteral nutrition-associated liver disease.

Parenteral nutrition (PN) is a therapy that delivers essential nutrients intravenously to patients who are unable to meet their nutrition requirements via standard enteral feeding. This methodology is often referred to as PN when accompanied by minimal or no enteral nutrition (EN). Although PN is lifesaving, significant complications can arise, such as intestinal failure-associated liver disease and gut-mucosal atrophy. The exact mechanism of injury remains ill defined. This review was designed to explore the available literature related to the drivers of injury mechanisms. The Farnesoid X receptor and fibroblast growth factor 19 signaling pathway seems to play an important role in gut-systemic signaling, and its alteration during PN provides insights into mechanistic links. Central line infections also play a key role in mediating PN-associated injury. Although lipid reduction strategies, as well as the use of multicomponent lipid emulsions and vitamin E, have shown promise, the cornerstone of preventing injury is the early establishment of EN.

Multi-Center Analysis of Predictive Factors of Enteral Autonomy and Risk Factors of Complications of Pediatric Intestinal Failure in China.

ObjectivesThe aim of this study was to identify predictors for enteral autonomy and intestinal failure (IF)-related complications and evaluate the outcomes of a multi-center pediatric cohort in China.MethodsThe medical records of pediatric patients with IF treated at four medical centers in China from January 1, 2012 to November 31, 2020 were retrospectively reviewed. Enteral autonomy was defined as sustained growth and cessation of parenteral nutrition for >90 days. Multivariate logistic regression analysis was used to identify factors predictive of enteral autonomy and the risk factors of complications, such as IF-associated liver disease (IFALD) and catheter-related bloodstream infection (CRBSI).ResultsThe study cohort of 92 pediatric patients with IF included 71 (77%) who underwent surgery and 21 (23%) who received non-surgical treatment. Eventually, 63 (68.5%) patients achieved enteral autonomy by the end of the follow-up period. Multivariate logistic regression analysis indicated that longer duration of parenteral nutrition (PN), sepsis, and non-breastfeeding were risk factors for enteral autonomy. When considering the detailed intraoperative data, the presence of an ileocecal valve (ICV) and greater residual small bowel (RSB) length were reaffirmed as predictors of achieving enteral autonomy. Medium/long-chain (MCT/LCT) lipids or sepsis were identified as negative predictors for IFALD. Univariate analysis revealed that the use of MCT/LCT lipids was associated with a greater likelihood of CRBSI.ConclusionIn this cohort, enteral autonomy was achieved at a percentage of 68.5%, and the risk factors for not achieving enteral autonomy were a longer duration of PN, sepsis, and non-breastfeeding. The presence of an ICV and a greater RSB length were important predictors of achieving enteral autonomy.

Intestinal failure-associated liver disease in the neonatal ICU: what we know and where we're going.

Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD. The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD. Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.

Real-world etiologies and treatments of pediatric short bowel syndrome in Japan.

Short bowel syndrome (SBS) is a rare disease that can result in intestinal failure (IF). Short bowel syndrome intestinal failure leads to stunted growth and development and high mortality rates. The primary goal of treatment is to enhance intestinal adaptation and nutrient absorption. Parenteral nutrition (PN) is used to support this process until enteral autonomy can be restored. Some patients experience prolonged partial or complete dependency on PN and face an increased risk of life-threatening catheter-related bloodstream infections and intestinal failure-associated liver disease. This study aimed to provide real-world insights into the patient characteristics and treatment dynamics of PN-dependent children with SBS-IF in Japan. This retrospective observational study used anonymized information from a large hospital-based medical insurance database to identify pediatric patients who received PN for ≥6 months between April 2008 and January 2020. The primary endpoint was weaning from PN. Secondary endpoints included duration and complications of PN. Forty-eight children (mean age, 2.9 years) were eligible for inclusion. The most common causes of SBS-IF were mechanical bowel obstruction, functional bowel disorders, and Hirschsprung's disease. Twenty-two patients (45.8%) were weaned from PN during the study. The mean time to first weaning was 464.2 days and five patients (22.7%) restarted PN. The mean total duration of PN was 692.6 days in weaned patients and 1,170.9 days in unweaned patients. The most frequent complications were sepsis, catheter infections (both 79.2%), and liver dysfunction (64.6%). Pediatric patients with SBS-IF faced difficulties when weaning off PN and rates of life-threatening complications were high.

RNA-sequencing identifies novel transcriptomic signatures in intestinal failure-associated liver disease

BackgroundTotal parenteral nutrition (TPN) dependence leads to development of intestinal failure-associated liver disease (IFALD). The spectrum of diseases ranges from cholestasis, steatosis, fibrosis, and cirrhosis that causes significant morbidity. Understanding the disease at molecular level helps us to develop therapeutic targets. We performed transcriptomic analysis on liver from rats with TPN administration, and we assessed the role of selected differentially expressed genes (DEGs), functional pathways, transcriptional factors, and their associations with pathological parameters of IFALD. MethodsSprague-Dawley rats were subjected to TPN or standard chow with 0.9% saline for 7 days as controls. RNA-seq analysis was performed on liver samples. Correlations between transcriptional factor hairy and enhancer of split 6 (Hes6) and pathological parameters of IFALD were investigated. ResultsWe provided a comprehensive transcriptomic analysis to identify DEGs and functional pathways in liver from TPN-fed rats. We identified solute carrier family 7 member 11 (Slc7a11) as the most up-regulated mRNA, and ferroptosis-associated pathways were enriched in TPN group. Transcriptional factor (TF) analysis revealed that Hes6 interacted with Nr1d1, Tfdp2, Zbtb20, and Hmgb2l1. TF target gene prediction analysis suggested that Hes6 may regulate genes associated with bile acid secretion and fatty acid metabolism. Last, hepatic Hes6 expression was significantly decreased in TPN-fed rats, and was positively correlated with several taurine-conjugated bile acids and negatively correlated with hepatic triglyceride level. ConclusionsRNA-seq analysis revealed unique transcriptomic signatures in the liver following TPN administration. Hes6 may be a critical regulator for IFALD pathogenesis.