Complication Of Long-term Parenteral Nutrition Research Articles

Predictive value of serum fibroblast growth factor 19 and liver stiffness for intestinal failure associated liver disease-cholestasis

BackgroundIntestinal failure associated liver disease (IFALD)-cholestasis is a common complication of long-term parenteral nutrition (PN) in patients with intestinal failure (IF). The lack of effective early identification indicators often results in poor clinical outcomes. The objective of this study was to evaluate the predictive value of serum FGF19 and liver stiffness in IFALD-cholestasis. MethodsEligible adults diagnosed with IF were identified from Jinling Hospital in China. Diagnostic criteria for IFALD-cholestasis: total bilirubin >1 mg/dL and conjugated bilirubin >0.3 mg/dL for ≥6 months. Fasting blood specimens were prospectively collected and serum FGF19 concentrations were determined using ELISA and liver stiffness was measured by Two-dimensional shear wave elastography. Binary logistic regression analysis identified predictors of IFALD-cholestasis. Receiver operating characteristic (ROC) curves and areas under the ROC curves (AUROC) were used to evaluate the accuracy of serum FGF19 and liver stiffness in identifying IFALD-cholestasis. ResultsOf 203 study patients with IF, 70 (34.5%) were diagnosed with IFALD-cholestasis. The serum FGF19 levels in those with IFALD-cholestasis were significantly decreased compared with those in patients without, and liver stiffness was significantly increased (p<0.001). Multivariate logistic regression analyses suggested that intestinal discontinuity, dependence on PN, liver stiffness >6.5 kPa, and serum FGF19 ≤107 pg/mL were independent risk factors for IFALD-cholestasis. The AUROC for serum FGF19 and liver stiffness, which indicate the occurrence of IFALD-cholestasis, were 0.810 and 0.714, respectively. Serum FGF19 had a superior predictive performance than liver stiffness (p<0.05). ConclusionBoth low circulating serum FGF19 concentration and increased liver stiffness are excellent predictors of IFALD-cholestasis, but serum FGF19 is superior to increased liver stiffness in predicting IFALD-cholestasis.

Risk factors for catheter-related bloodstream infections associated with home parental nutrition in children with intestinal failure: A prospective cohort study

Catheter-related bloodstream infection (CRBSI) is the most common, potentially life-threatening complication of long-term parenteral nutrition (PN). We prospectively assessed the incidence and risk factors for CRBSI in children receiving long-term home PN (HPN) for intestinal failure (IF) in a single IF rehabilitation center. Data regarding episodes and potential risk factors for CRBSI in children on HPN were prospectively recorded. Forty-one of 75 children were diagnosed with CRBSI. The overall CRBSI rate was 1.61 per 1000 catheter days. The indications for HPN were gastrointestinal motility disorders in 35%, short bowel syndrome (SBS) in 28% graft versus host disease (GvHD) post bone marrow transplant in 17%, congenital enteropathy in 15%, and severe neurodevelopmental impairment in 5%. Gastrointestinal motility disorders had significantly higher CRBSI rate compared to other groups (p<0.0005; 2.74 in motility group vs 1.54 in GvHD group vs 0.52 in congenital enteropathies vs 0.36 in SBS group vs 0.67 in severe neurodevelopmental delay). Multivariate analysis revealed that enterocutaneous distal stoma (ileostomy or colostomy) (HR 3.35 [95% CI, 1.63-6.86]; p<0.001), age <2 years (HR 0.28 [95% CI, 0.15-0.53]; p<0.0001), male sex (HR 2.28 [95% CI, 1.51-3.43]; p<0.0001), non-use of taurolidine citrate lock (HR 2.70 [95% CI, 1.72-4.11]; p<0.0001) and gastrointestinal motility disorder (HR 3.02 [95% CI, 1.81-4.91]; p<0.001) were independent risk factors for developing CRBSI. Extra care in managing PN connections and disconnections should be taken in children with an underlying gastrointestinal motility disorder, distal enterocutaneous stoma, male sex and those aged <2 years since they are at a significantly higher risk of CRBSI. Early introduction of taurolidine lock should be considered.

Activity of aminotransferases as a marker of liver injury in home parenteral nutrition patients.

Aim of the studyParenteral nutrition associated liver disease (PNALD) is a frequently reported complication of long-term parenteral nutrition. Early diagnosis and treatment of PNALD can help prevent end-stage liver disease. The aim of the study was to evaluate the activity of aminotransferases as a marker of liver dysfunction in patients receiving home parenteral nutrition under the care of a reference center.Material and methodsA comprehensive analysis of patients’ medical records from a 9-year period (December 2012 – December 2021) was conducted and the following parameters were evaluated: parenteral nutrition mixture composition, total plasma bilirubin, activity of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), standardized time factor prothrombin (international normalized ratio [INR] factor) and serum albumin. The analysis covered 630,537 days of parenteral nutrition. The study included 251 patients (140 women and 111 men) included in the Home Parenteral Nutrition Program.ResultsPNALD was diagnosed in 11 parenteral fed patients, which gives the frequency of 8.3%/9 years of treatment. Two deaths were classified as cause of death related to liver disease but not related to PNALD. None of the patients included in the analysis developed end-stage liver failure.ConclusionsThe above analysis shows that individual selection of the composition of the mixture for intravenous nutrition significantly reduces the risk of PNALD and may prevent liver failure in this context.

Alterations of gut microbiota and serum bile acids are associated with parenteral nutrition-associated liver disease

BackgroundParenteral nutrition-associated liver disease (PNALD) is a major complication of long-term parenteral nutrition (PN). The pathogenesis of PNALD remains unclear. We investigated the changes in taxonomic and functional composition of gut microbiota and serum bile acid levels in a rat model of PNALD. MethodsMale 4-week-old Sprague Dawley rats received either total parenteral nutrition or standard chow with 0.9% saline for 7 days. The taxonomic composition of cecal microbiota and its functional composition associated with bile acid metabolism were measured. ResultsThere were differences in taxonomic composition between the two groups. The abundance of the secondary bile acid biosynthesis pathway was higher in the TPN group (p < 0.05) with an increase in the percentage of bacteria expressing 7-alpha-hydroxysteroid dehydrogenase (p < 0.05). The abundance of enzymes associated with bile salt hydrolase was also higher (p < 0.05) in the TPN group. The TPN group showed a distinct bile acid profile characterized by a higher ratio of secondary bile acids to primary bile acids. ConclusionsThe alteration of bile acid-associated microbiota may lead to increased secondary bile acid production in a rat model of PNALD.

Monitoring of long-term parenteral nutrition in children with intestinal failure.

Pediatric intestinal failure (IF) is a rare and complex condition associated with significant morbidity and mortality. It is defined as the reduction of gut mass or function below the minimal needed for absorption of nutrients and fluid to sustain life and growth. Since the advent of specialized multidisciplinary intestinal rehabilitation centers, IF management has considerably evolved in the last years, but serious complications of long‐term parenteral nutrition (PN) can occur. Main complications include intestinal failure‐associated liver disease, growth failure, body composition imbalance, central venous access complications, micronutrient deficiencies and toxicities, metabolic bone disease, small intestinal bacterial overgrowth, and renal disease. With improvement in survival rates of patients over the last 20 years, emphasis should be on limiting IF‐related comorbidities and improving quality of life. Close monitoring is pivotal to ensuring quality of care of these patients. The care of children with chronic IF should involve a comprehensive monitoring plan with flexibility for individualization according to specific patient needs. Monitoring of children on long‐term PN varies significantly across units and is mainly based on experience, although few guidelines exist. This narrative review summarizes the current knowledge and practices related to monitoring of children with IF. The authors also share their 20‐year experience at the Royal Children's Hospital in Melbourne Australia on this topic.

Visceral transplantation in patients with intestinal-failure associated liver disease: Evolving indications, graft selection, and outcomes.

Intestinal failure (IF)-associated liver disease (IFALD) is widely recognized as a lethal complication of long-term parenteral nutrition. The pathophysiology of IFALD is poorly understood but appears to be multifactorial and related to the inflammatory state in the patient with IF. Visceral transplant for IFALD includes variants of intestine, liver, or combined liver-intestine allografts. Graft selection for an individual patient depends on the etiology of IF, abdominal and vascular anatomy, severity of IFALD, and potential for intestinal rehabilitation. The past decade has witnessed dramatic improvement in the management of IFALD, principally due to improved lipid emulsion formulations and the multidisciplinary care of the patient with IF. As the recognition and treatment of IFALD continue to improve, the requirement of liver-inclusive visceral grafts appears to be decreasing, representing a paradigm shift in the care of the patient with IF. This review highlights the current indications, graft selection, and outcomes of visceral transplantation for IFALD.

Long-term outcomes of pediatric intestinal failure

Management of pediatric intestinal failure has evolved in recent decades, with improved survival since the advent of specialized multidisciplinary intestinal failure centers. Though sepsis and intestinal failure associated liver disease still contribute to mortality, we now have growing data on the long-term outcomes for this population. While intestinal adaptation and parenteral nutrition weaning is most rapid during the first year on parenteral support, achievement of enteral autonomy is possible even after many years as energy and protein requirements decline dramatically with age. Intestinal transplant is an option for patients experiencing complications of long-term parenteral nutrition who are expected to have permanent intestinal failure, but outcomes are hindered by immunosuppression-related complications. Much of the available data comes from single center retrospective reports, with variable inclusion criteria, intestinal failure definitions, and follow-up durations; this limits the ability to analyze outcomes and identify best practices. As most children now survive long-term, the focus of management has shifted to the avoidance and management of comorbidities, support of normal growth and development, and optimization of quality of life for these medically and surgically complex patients.

長期間の中心静脈カテーテル留置が原因となった巨大右房血栓症の 1 例

長期間の中心静脈カテーテル留置が原因となった巨大右房血栓症の 1 例

Aseptic non-touch technique and catheter-related bloodstream infection in children receiving parenteral nutrition at home.

Parenteral nutrition (PN) at home is an acceptable form of delivering long-term PN for children with intestinal failure. Catheter-related bloodstream infection (CRBSI) is one of the serious complications of long-term PN and can lead to increasing morbidity and mortality. Using aseptic non-touch technique (ANTT) was proven to decrease the incidence of CRBSI in hospital patients. In this study we aimed to review the incidence of CRBSI in children receiving PN at home in our institution using the ANTT and a simplified training programme for parents and carers. We retrospectively collected clinical and microbiological data on all children with intestinal failure (IF) who were on treatment with PN at home under our specialist IF rehabilitation service between November 2012 and November 2013. Thirty-five children were included, 16 of whom did not have any infection recorded during the study period. The overall CRBSI rate was 1.3 infections per 1000 line-days, with Staphylococcus being the commonest organism. Twenty-one children did not require catheter change and the overall catheter changes were 1.8 per 1000 line-days. In this article, we report a low incidence of CRBSI in a single institution by using the principle of ANTT for accessing central venous catheters combined with a simplified, nurse-led, two-week standardised training programme for parents of children going home on PN.

PTH-219 Prevalence of intestinal failure-associated liver disease within a home parenteral nutrition service

Introduction Intestinal failure-associated liver disease (IFALD) is a potentially life-threatening and historically common complication of long-term parenteral nutrition. In the past two decades advances in catheter sepsis prevention and the development of novel lipid formulations have reduced the prevalence of IFALD. We examined the point prevalence of surrogate markers of IFALD within the home parenteral nutrition (HPN) service at the Royal Berkshire Hospital. Method The records of the HPN service were examined to identify patients receiving HPN between January 2012 and December 2014. Clinic notes, electronic patient records and imaging results were used to extract clinical information. Results Twenty-four patients (13 male; mean age 60 years, range 21–83 years) received long-term home parenteral nutrition during the study period for a mean duration of 25 months (range 3–54 months). Underlying causes of intestinal failure included inflammatory bowel disease (7, 29%), vascular causes (5, 21%), surgical complications including fistulae, sepsis and adhesions (5, 21%), malignancy (4, 17%) and dysmotility (3, 12%). Most patients received a tailor-made PN bag 3–7 days a week (median 5 days a week) with a lipid emulsion (SMOF) bag twice a week. In this cohort 16 patients had persistently abnormal liver biochemistry (raised ALT and/or ALP greater than the reference range for longer than six months). Two patients had mildly elevated bilirubin (1–2 x upper limit of normal). There were no clinical presentations of decompensated liver disease. Nineteen patients had hepatic imaging (ultrasound or CT) during the study period. One patient had splenomegaly secondary to portal vein thrombosis and one patient had ascites related to Budd-Chiari syndrome. No other patients had radiological signs of portal hypertension or cirrhosis on imaging. Three patients underwent transient elastography measurement (Fibroscan ® ) one of which had an elevated reading (10.7kPa, IQR 1.5). Conclusion These results show that two thirds of patients on long-term parenteral nutrition had persistent abnormalities in liver biochemistry which may indicate steatohepatitis. No patients showed signs of cirrhosis on imaging or presented with decompensated liver disease during the three-year study period. Whilst this is a relatively short follow-up period to detect the development of chronic liver disease, previous studies have reported a prevalence of complicated liver disease of 26% after two years of PN. 1 We plan to prospectively monitor liver biochemistry, abdominal imaging and transient elastography in our HPN cohort to assess the natural history of IFALD. Disclosure of interest None Declared. Reference Cavicchi M et al . Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med. 2000;132:525–532

Low-fat, high-carbohydrate parenteral nutrition (PN) may potentially reverse liver disease in long-term PN-dependent infants.

Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen, which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids. Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from carbohydrates. The fat-free PN, containing 314 kJ/ml, was provided 5-6 times a week and fat, including essential fatty acids and fat-soluble vitamins, 1-2 times a week. Enteral feeding was continued according to individual tolerance. The study included 10 infants with short bowel syndrome (six with intestinal failure due to necrotizing enterocolitis, one with gastroschisis, one with complications due to unrecognized anal atresia and two with midgut volvulus). Median duration of PN with fat before initiating the low-fat regime was 69 days (25-75 % percentile: 41-75 days), and mean s-bilirubin was 139 µmol/l (range 87-323 µmol/l). Median duration with low-fat regimen was 69 days (25-75 % percentile: 18-123 days). Bilirubin reversed to normal (<50 µmol/l) in all infants. Seven children showed catch-up growth. No essential fatty acid deficiency, steatosis or deaths were observed. A low-fat, high-carbohydrate PN regimen together with enteral feeding is well tolerated and may be used in reversing liver disease in PN-dependent infants without compromising growth.

Decreased Bone Turnover Markers in Children on Long‐Term Parenteral Nutrition (PN) for Intestinal Failure (IF)

Metabolic bone disease (MBD) is a well-recognized but poorly understood complication of long-term parenteral nutrition (PN). Bone histomorphometry in adults has provided useful information but does not provide quantitative measures of bone resorption and is to invasive for children. Measurement of bone turnover markers provides an alternative less invasive approach. We therefore aimed to measure bone turnover markers in children on long-term PN for intestinal failure (IF), and to compare them to age- and gender-matched controls. Serum concentrations of osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and c-telopeptide (CTx) were measured in IF patients treated at a multidisciplinary intestinal rehabilitation and home PN program at the Hospital for Sick Children, Toronto, Canada. Age- and gender-matched control participants were recruited for comparison. A total of 13 IF patients and 20 control participants were recruited. IF patients had lower serum OC and CTx concentrations when compared with controls: 42.43 ± 11.54 vs 68.39 ± 20.95 µg/L (P < .01) and 7.454 ± 2.17 vs 9.246 ± 1.92 (P < .05; mean ± SD) µg/L for OC and CTx, respectively. In a subgroup of 9 IF patients for whom BMD was available, OC and CTx concentration were negatively correlated to BMD (g/cm(2)) and BMD z score. Bone turnover markers may be useful indicators for identifying children on long-term PN at risk of MBD. Further studies are needed to validate the current results and determine the factors that influence the occurrence and evolution of MBD in children on PN.

Provision of a Soy‐Based Intravenous Lipid Emulsion at 1 g/kg/d Does Not Prevent Cholestasis in Neonates

One of the most common and severe complications of long-term parenteral nutrition (PN) is PN-associated cholestasis. The soybean oil-based lipid emulsion administered with PN has been associated with cholestasis, leading to an interest in lipid reduction strategies. The purpose of this study was to determine whether the provision of a soybean oil-based lipid emulsion at 1 g/kg/d compared with 2-3 g/kg/d is associated with a reduced incidence of cholestasis. Retrospective review of neonates admitted between 2007 and 2011 with a gastrointestinal condition necessitating ≥ 21 days of PN support. Neonates were divided into 2 groups based on the intravenous lipid emulsion dose: 1-g group (1 g/kg/d) and 2- to 3-g group (2-3 g/kg/d). The primary outcome measure was the incidence of cholestasis. Sixty-one patients met inclusion criteria (n = 29, 1-g group; n = 32, 2- to 3-g group). The 2 groups did not differ in any baseline characteristics other than associated comorbidities that were more common in the 2- to 3-g group. The duration of PN, the number of operative procedures and bloodstream infections, and enteral nutrition (EN) were similar between groups. The incidence of cholestasis was not different between groups (51.7%, 1-g group; 43.8%, 2- to 3-g group; P = .61), and there was no difference between groups in the time to cholestasis (32.6 ± 24.1 days, 1-g group; 27.7 ± 10.6 days, 2- to 3-g group; P = .48). Overall, 44.8% of patients with cholestasis were transitioned to full EN, and 55.2% were transitioned to a fish oil-based lipid emulsion after which the direct bilirubin normalized in all patients. Lipid reduction to 1 g/kg/d does not prevent or delay the onset of cholestasis in neonates.

Prevention of parenteral nutrition-associated liver disease: role of ω-3 fish oil

Parenteral nutrition-associated liver disease (PNALD) is the most severe complication of long-term parenteral nutrition. Its cause remains unclear, although recent studies suggest that the omega-6 polyunsaturated fatty acids in plant oil-based lipid emulsions and the associated phytosterols contribute to the development of hepatotoxicity. In contrast, fish oil-based lipid emulsions are composed mainly of omega-3 polyunsaturated fatty acids and are hypothesized to be hepatoprotective. This review will discuss fish oil-based lipid emulsions in the prevention of PNALD. In several animal models of PNALD, the use of an intravenous fish oil-based lipid emulsion improved parenteral nutrition-associated cholestasis without resultant essential fatty acid deficiency or growth impairment. Following these results and preliminary human data, an open trial for compassionate use was initiated, followed by a randomized controlled trial to evaluate the current management of pediatric PNALD. To date, at the author's institution, more than 130 children with PNALD have been treated with Omegaven, a fish oil-based emulsion, with improved liver function among most patients. PNALD remains the most severe complication of long-term parenteral nutrition with an unclear pathophysiology. However, the use of a fish oil-based emulsion appears efficacious and hepatoprotective.

Fish Oil–Based Lipid Emulsions Prevent and Reverse Parenteral Nutrition–Associated Liver Disease: The Boston Experience

Parenteral nutrition-associated liver disease (PNALD) is the most prevalent and most severe complication of long-term parenteral nutrition. Its underlying pathophysiology, however, largely remains to be elucidated. The currently approved parenteral lipid emulsions in the United States contain safflower or soybean oils, both rich in omega-6 polyunsaturated fatty acids (PUFAs). Mounting evidence indicates that the omega-6 PUFAs originating from plant oils in these lipid emulsions may play a role in the onset of liver injury. Fish oil-based lipid emulsions, in contrast, are primarily composed of omega-3 PUFAs, thus providing a promising alternative. The authors review the literature on the role of lipid emulsions in the onset of PNALD and discuss prevention and treatment strategies using a fish oil-based lipid emulsion. They conclude that a fish oil-based emulsion is hepatoprotective in a murine model of PNALD, and it appears to be safe and efficacious for the treatment of this type of liver disease in children. A prospective randomized trial that is currently under way at the authors' institution will objectively determine the place of fish oil monotherapy in the prevention of PNALD.

Thromboembolism in Infants and Children With Gastrointestinal Failure Receiving Long‐Term Parenteral Nutrition

Thromboembolism is an established complication of long-term parenteral nutrition (PN) administration which requires central venous lines in the pediatric population. Predisposing factors that increase the risk of thrombosis, as well as prophylaxis and treatment guidelines in this specific population, are not clearly defined. We performed a computerized search of PubMed, OVID databases, and pertinent articles from reference lists of related review papers. This review summarizes currently available data on the rates of thromboembolism in the pediatric population receiving long-term PN and concludes that control of factors such as location of catheter, duration of nutrition support, and prophylaxis with heparin or anticoagulants may reduce the rates of thrombosis in this patient population, although most data on the matter are inconclusive.

Long-term parenteral nutrition

Summary Parenteral nutrition (PN) represents a life-saving intervention for children with intestinal failure (IF). Following initial hospitalisation, management at home offers a good quality of life. The techniques for providing safe and effective PN are well established, although many are based on expert opinion rather than randomised, controlled trials. Catheter-related bloodstream infection, IF-associated liver disease and venous thrombosis remain the most common serious complications of long-term PN. Supervision by multidisciplinary nutritional support teams allows optimisation of risks and benefits. When complications are life threatening in nature, consideration should be given to intestinal transplantation. In the only UK centre performing this surgery, 5-year survival at the present time is 52%.

Parenteral nutrition-associated metabolic bone disease.

The incidence of parenteral nutrition-associated metabolic bone disease is unknown. Initial reports from the early 1980s suggested that both osteoporosis and osteomalacia were quite common in patients who receive long-term parenteral nutrition. The findings described in these early surveys provide a snapshot into the many factors that contribute to the development of metabolic bone disease. More recent evidence suggests that bone loss may not be as great with the initiation of parenteral nutrition as once was thought, and that most of the metabolic bone disease that is noted may be related to the patient's underlying illness. Although this recent information is reassuring, it is of the utmost importance to provide parenteral nutrition that minimizes further bone loss and promotes the formation of new bone. This review will describe the general features of metabolic bone disease and the abnormalities noted with parenteral nutrition-associated metabolic bone disease, highlight the importance of preexisting illness and parenteral nutrition associated factors that contribute to the development of metabolic bone disease, and finally discuss an approach to avoid this debilitating complication of long-term parenteral nutrition.

Cholestatic jaundice in newborn infants receiving parenteral nutrition

Hepatic cholestasis is a common complication of long-term parenteral nutrition in infants and children. The factors contributing to the development of this complication are multifactorial and not yet completely determined. Neonates, especially those born preterm, are at particular risk. Infection, intestinal bacterial overgrowth and lack of enteral stimulation contribute significantly to the development of the disease. The data on direct toxicity of parenteral nutrients is contradictory and mainly based on experimental animal models that do not reproduce the liver damage observed in infants and children. Enteral feedings should be started as soon as possible to prevent parenteral nutrition-related cholestasis. The efficacy of various drug treatments in preventing parenteral nutrition-related cholestasis have not been proved.

Calcified thrombus in the right atrium: A rare complication of long-term parenteral nutrition in a child

A 5-year-old boy with short-bowel syndrome who receives home parenteral nutrition developed a calcified thrombus that involved the inferior vena cava (IVC) and the right atrium. Symptoms included 3 to 4 months of intermittent fever and 2 months of vague chest pain. Blood could not be aspirated from the IVC catheter and an IVC contrast study demonstrated the calcified thrombus. The intracardiac portion of the mass was removed surgically, but the IVC mass could not be completely excised. The boy developed a pericardial effusion 6 weeks after surgery. He was treated for this and 6 months after the initial surgery the patient was asymptomatic.