Neurodevelopmental Outcome of Extremely Low Birth Weight Infants with Cholestasis at 12 and 24 Months.

INTRODUCTION: The aims of the study were to describe the neurodevelopmental outcome of extremely low birth weight (ELBW) infants with parenteral nutrition-associated cholestasis (PNAC) and to assess whether PNAC is associated with adverse neurodevelopmental outcome. METHODS: The study is a secondary analysis of controlled trial (June 2012-October 2017) on PNAC incidence in ELBW infants receiving two different parenteral lipid emulsions (mixed lipid emulsion containing fish oil vs. soybean oil-based). Neurodevelopmental follow-up at 12- and 24-month corrected age was compared in infants with and without PNAC. A machine learning-based regression analysis was used to assess whether PNAC was associated with adverse neurodevelopmental outcome. RESULTS: For assessment of neurodevelopmental outcome (Bayley-III), 174 infants were available at 12-month (PNAC: n = 21; no PNAC: n = 153) and 164 infants at 24-month (PNAC: n = 20; no PNAC: n = 144) corrected age. The neurodevelopment of ELBW infants with PNAC was globally delayed, with significantly lower cognitive, language, and motor scores at both 12- and 24-month corrected age. Regression analyses revealed that PNAC was associated with an adverse motor outcome. CONCLUSION: ELBW infants with PNAC are at increased risk for adverse neurodevelopmental outcome.

Malnutrition in Pediatric Chronic Cholestatic Disease: An Up-to-Date Overview.

Despite recent advances, the causes of and effective therapies for pediatric chronic cholestatic diseases remain elusive, and many patients progress to liver failure and need liver transplantation. Malnutrition is a common complication in these patients and is a well-recognized, tremendous challenge for the clinician. We undertook a narrative review of both recent and relevant older literature, published during the last 20 years, for studies linking nutrition to pediatric chronic cholestasis. The collected data confirm that malnutrition and failure to thrive are associated with increased risks of morbidity and mortality, and they also affect the outcomes of liver transplantation, including long-term survival. Malnutrition in children with chronic liver disease is multifactorial and with multiple potential nutritional deficiencies. To improve life expectancy and the quality of life, patients require careful assessments and appropriate management of their nutritional statuses by multidisciplinary teams, which can identify and/or prevent specific deficiencies and initiate appropriate interventions. Solutions available for the clinical management of these children in general, as well as those directed to specific etiologies, are summarized. We particularly focus on fat-soluble vitamin deficiency and malnutrition due to fat malabsorption. Supplemental feeding, including medium-chain triglycerides, essential fatty acids, branched-chain amino acids, and the extra calories needed to overcome the consequences of anorexia and high energy requirements, is reviewed. Future studies should address the need for further improving commercially available and nutritionally complete infant milk formulae for the dietary management of this fragile category of patients. The aid of a specialist dietitian, educational training regarding nutritional guidelines for stakeholders, and improving family nutritional health literacy appear essential.

Morbidity Outcomes of Very Low Birth Weight Neonates Receiving Parenteral Nutrition with Fish Oil Enriched Lipid Emulsion or Lipid Emulsion with Soybean Oil: An Observational Study.

Intralipid (Fresenius Kabi) was the most commonly used lipid emulsion in parenteral nutrition (PN), with a 100% soybean oil composition, a low vitamin E content, and a ω-6: ω-3 ratio of 7:1. A recent alternative formulation is SMOFlipid (Fresenius Kabi), with a ω-6: ω-3 ratio of 5:2 and higher vitamin E content. A retrospective observational study was conducted to determine neonatal morbidity in very low birth weight (VLBW) premature infants during two periods: P1, when PN was based exclusively on Intralipid, and P2, when only SMOFlipid was supplied. In total, 170 VLBW neonates were analyzed, of whom 103 received PN for more than 6 days, 56 during P1, and 47 during P2. In both periods, the antenatal and neonatal characteristics of the cohort were comparable. In this analysis, the prevalence of associated comorbidities was determined. During P2, there were fewer cases of moderate to severe bronchopulmonary dysplasia (BPD) and of cholestasis, but more cases of late sepsis, mainly Staphylococcus epidermidis. No changes in the prevalence of other neonatal comorbidities were observed. We believe that the SMOFlipid used in PN could discreetly improve the prevalence of cholestasis or BPD.

Incidence of Complications Associated with Parenteral Nutrition in Preterm Infants < 32 Weeks with a Mixed Oil Lipid Emulsion vs a Soybean Oil Lipid Emulsion in a Level IV Neonatal Intensive Care Unit.

BACKGROUND: Parenteral nutrition (PN) is crucial for the improvement of long-term outcomes in very low birth weight (VLBW) neonates. Lipid injectable emulsions are a key component of PN, as they contain essential fatty acids and provide energy critical for brain growth. Prolonged administration increases risk of intestinal failure-associated liver disease, including cholestasis, and other complications. METHODS: This is a retrospective, quasi-experimental cohort study of 215 VLBW neonates. The primary outcome was a change in direct bilirubin concentration. Secondary outcomes included change in total bilirubin concentration and incidences of cholestasis and other disease states associated with PN and prematurity. Cholestasis was defined as direct bilirubin ≥ 1.0 mg/dL with total bilirubin < 5.0 mg/dL or direct bilirubin > 20% of total bilirubin with total bilirubin > 5.0 mg/dL. RESULTS: Change in direct bilirubin concentration was not different between groups. Incidence of cholestasis was not different between groups per charted diagnosis or per study definition. Non-stage-0 retinopathy of prematurity, bronchopulmonary dysplasia, sepsis, and necrotizing enterocolitis were all lower in the mixed oil lipid emulsion group, which remained significant after adjustment for differences in gestational age, birth weight, and PN duration. CONCLUSIONS: Although mixed oil lipid emulsion was not found to be associated with a lower risk of cholestasis, it may decrease risks of other disease states associated with PN therapy.

SMOFlipid vs Intralipid 20%: Effect of Mixed-Oil vs Soybean-Oil Emulsion on Parenteral Nutrition-Associated Cholestasis in the Neonatal Population.

BACKGROUND: Parenteral nutrition (PN) is critical for the growth and development of premature neonates who are unable to reach nutrition goals enterally. Using soybean-oil emulsions in PN is a risk factor for cholestasis, leading to alternative dosing strategies including a reduction in total lipid prescribed. Recently, SMOFlipid has been utilized with the goal of avoiding cholestasis while maintaining energy intake. The aim of our study was to compare the incidence of PN-associated cholestasis (PNAC) in patients admitted to the neonatal intensive care unit (NICU) who received either Intralipid 20% or SMOFlipid. METHODS: This single-center, retrospective study evaluated all NICU patients who received PN for ≥14 days. Patients who received SMOFlipid were compared with those who received Intralipid. The primary end point was incidence of PNAC. Secondary end points included (1) prevalence of elevated liver function tests; (2) effect on select laboratory parameters; (3) development of PNAC by age; and (4) incidence of retinopathy of prematurity. RESULTS: A total of 136 neonates were included. Nine of 55 patients (16.4%) in the Intralipid group and 2 of 81 patients (2.5%) in the SMOFlipid group developed cholestasis, defined as direct bilirubin > 2 mg/dL or direct bilirubin > 20% of total bilirubin, when total bilirubin is >5 mg/dL, on or before 30 days post initiation of PN (P = .007). CONCLUSION: Use of SMOFlipid as the lipid emulsion component of PN may be beneficial in prevention of PNAC in NICU patients that are receiving PN for ≥2 weeks.

Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors.

BACKGROUND: Bodybuilding supplements can cause a profound cholestatic syndrome. AIM: To describe the drug-Induced liver injury network's experience with liver injury due to bodybuilding supplements. METHODS: Liver injury pattern, severity and outcomes, potential genetic associations, and exposure to anabolic steroids by product analysis were analysed in prospectively enrolled subjects with bodybuilding supplement-induced liver injury with causality scores of probable or higher. RESULTS: Forty-four males (mean age 33 years) developed liver injury with a median latency of 73 days. Forty-one per cent presented with hepatocellular pattern of liver injury as defined by the R > 5 ([Fold elevation of ALT] ÷ [Fold elevation of Alk Phos] (mean, range = 6.4, 0.5-31.4, n = 42) despite all presenting with clinical features of cholestatic liver injury (100% with jaundice and 84% with pruritus). Liver biopsy (59% of subjects) demonstrated a mild hepatitis and profound cholestasis in most without bile duct injury, loss or fibrosis. Seventy-one per cent were hospitalised, and none died or required liver transplantation. In some, chemical analysis revealed anabolic steroid controlled substances not listed on the label. No enrichment of genetic variants associated with cholestatic syndromes was found, although mutations in ABCB11 (present in up to 20%) were significantly different than in ethnically matched controls. CONCLUSIONS: Patients with bodybuilding supplements liver injury uniformly presented with cholestatic injury, which slowly resolved. The ingested products often contained anabolic steroids not identified on the label, and no enrichment in genetic variants was found, indicating a need for additional studies.

Effects of two different lipid emulsions on antioxidant status, lipid peroxidation and parenteral nutrition- related cholestasis in premature babies, a randomized-controlled study.

BACKGROUND: Olive oil-soybean oil (OO/SO) based lipid emulsions (LE) lack ω-3 PUFAs eicosapentaenoic acid -EPA and docosahexaenoic acid- DHA, which have clinical benefits on inflammatory processes. Fish oil based LEs are good sources of DHA and EPA. Fish oil, MCT, Olive oil and Soya oil (FMOS) lipid is one of the fish oil containing LEs supplemented with high levels of α-tocopherol and lower levels of phytosterol compared to OO/SO lipid emulsions. We investigated the effects of OO/SO and FMOS lipid preparations on cholestasis, levels of antioxidant enzymes and lipid peroxidation. METHODS: Preterm neonates ≤32 gestational weeks age and/or ≤1500 g were randomly assigned to receive either FMOS or OO/SO in the first day of life. Catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS) levels in the first day of life, 7th day of lipid use and 28th day of life were measured and cholestasis during parenteral nutrition was recorded. RESULTS: 34 and 33 patients were in FMOS and OO/SO lipid groups respectively. Although the TBARS levels were higher in the first day of life and 7th day of LEs in OO/SO lipid group (p=0.014 and p=0.022), on the 28th day of life TBARS level was similar and SOD level was higher (p=0.014) in OO/SO group. Cholestasis was significantly lower in FMOS lipid group (0% vs. 18.2%), (p=0.011) and neonates regained birth weight earlier (p=0.006). There was no significant difference in other morbidities. CONCLUSIONS: FMOS and OO/SO lipid emulsions have similar effects on lipid peroxidation on 28th day of life and on morbidities in short term period except for cholestasis.

Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill Children and the Impact of Delaying Parenteral Nutrition.

OBJECTIVES: In the Early versus Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial, delaying parenteral nutrition to beyond day 7 (late parenteral nutrition) was clinically superior to supplemental parenteral nutrition initiated within 24 hours (early parenteral nutrition), but resulted in a higher rise in bilirubin. We aimed to document prevalence and prognostic value of abnormal liver tests in the PICU and the impact hereon of withholding early parenteral nutrition. DESIGN: Preplanned secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial. Total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase plasma concentrations were measured systematically in PICU. Liver test analyses were adjusted for baseline characteristics including severity of illness. SETTING: Three PICUs in Belgium, the Netherlands, and Canada. PATIENTS: As neonatal jaundice was considered a confounder, only the 1,231 of the 1,440 Early versus Late Parenteral Nutrition in the Pediatric ICU-patients 28 days to 17 years old were included. INTERVENTIONS: Late parenteral nutrition as compared with early parenteral nutrition. MEASUREMENTS AND MAIN RESULTS: During the first seven PICU days, the prevalence of cholestasis (> 2 mg/dL [34.2 µmol/L] bilirubin) ranged between 3.8% and 4.9% and of hypoxic hepatitis (≥ 20-fold upper limit of normality for alanine aminotransferase and aspartate aminotransferase) between 0.8% and 2.2%, both unaffected by the use of parenteral nutrition. Throughout the first week in PICU plasma bilirubin concentrations were higher in late parenteral nutrition patients (p < 0.05), but became comparable to early parenteral nutrition patients as soon as parenteral nutrition was started on day 8. Plasma concentrations of gamma-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were unaffected by parenteral nutrition. High day 1 plasma concentrations of gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase (p ≤ 0.01), but not alkaline phosphatase, were independent risk factors for PICU mortality. Day 1 plasma bilirubin concentrations displayed a U-shaped association with PICU mortality, with higher mortality associated with bilirubin less than 0.20 mg/dL and greater than 0.76 mg/dL (< 3.42 µmol/L and > 13 µmol/L) (p ≤ 0.01). CONCLUSIONS: Overt cholestasis and hypoxic hepatitis were rare and unrelated to the nutritional strategy. However, withholding parenteral nutrition up to 1 week in PICU increased plasma bilirubin. A mild elevation of bilirubin on the first PICU day was associated with lower risk of death and may reflect a stress response, rather than true cholestasis.

Evaluation of vitamin D status bone mineral density and dental health in children with cholestasis.

BACKGROUND: Hepatic osteodystrophy caused by vitamin D and calcium malabsorption is thought to develop in children with cholestatic liver disease leading to secondary hyperparathyroidism and rickets or osteomalacia. The aim of this study was to evaluate the dental and bone mineral densities and the serum level of vitamin D in cholestatic infants and children and to correlate this process with clinical and laboratory parameters. METHODS: This is a cross-sectional study that include 50 patients presenting with cholestasis. Thirty age and sex matched controls recruited not complaining of liver disease. All cases were subjected to full history taking, clinical and dental examination, 25(OH)D level, ALT, AST, bilirubin, albumin, GGT, alkaline phosphatase, PT, INR, calcium, corrected calcium, phosphorus and DXA scan to those above 5 years old. Controls were subjected to measuring the serum levels of 25(OH)D, total bilirubin, direct bilirubin, ALT, GGT, AST, PT, INR, alkaline phosphatase, albumin, calcium and phosphorus. RESULTS: Out of the 50 cases; 23 were females (46%), with a mean age of 6.17±3.9 years ranging from 1.1 to 17 years. Twenty-eight of the cases had signs of rickets (56%), 6 of them had bone fracture (12%) and 42.8% had milky teeth caries. The level of 25(OH) vitamin D was below normal range in around half of the patients. There was significant difference between cases and controls in calcium and phosphorus levels, ALT and alkaline phosphatase. Low bone mineral density (BMD) was present in 50% and 5 cases (17.9%) were diagnosed as having osteoporosis. There was a negative correlation between the Z-score, BMD of total body, BMD and bone mineral content (BMC) of spine and total and direct bilirubin. There was a positive correlation between (BMD of total body, spine and BMC of spine) and serum phosphorus, alkaline phosphatase and albumin. There was a positive correlation between the Z-score of total body and serum calcium. CONCLUSION: Decreased level of 25-OH vitamin D is present in more than half of cholestatic patients, and is correlated positively to serum calcium. Decreased BMD was present in more than half of studied cholestatic patients correlated to the low serum calcium rather than the vitamin D level. The decreased BMD and the dental affection in cholestatic children is related to the level of hyperbilirubinemia.

Normal Growth and Essential Fatty Acid Status in Children With Intestinal Failure on Lipid Limitation.

OBJECTIVES: Lipid limitation, that is, ≤1 g · kg⁻¹ · day⁻¹ of soy oil lipid emulsion (SOLE), has been suggested as a method to reduce the risk of intestinal failure (IF)-associated liver disease (IFALD). There are limited data as to the effects of this strategy on growth and essential fatty acid (EFA) status. The aim of the study was to assess growth, prevalence of cholestasis, and EFA deficiency in patients with IF who were provided daily SOLE at a dose ≤1 g · kg⁻¹ · day⁻¹. METHODS: Medical records were retrospectively reviewed from 9 patients age 16 months to 8 years who had IF requiring parenteral nutrition support for >12 months. Parenteral nutrition supplied a mean of 53% of total energy (range 24%-86%). RESULTS: Mean SOLE dose was 0.61 g · kg⁻¹ · day⁻¹ (range 0.4-0.81 g · kg⁻¹ · day⁻¹). After 1 month of lipid limitation between 2011 and 2014, no patient developed IFALD as defined by a direct bilirubin >2 mg/dL. The median direct bilirubin was 0.1 mg/dL (range 0.075-0.85 mg/dL). No patient developed EFA deficiency as defined by a triene-to-tetraene ratio >0.2 (median 0.026, range 0.017-0.076). Height z scores increased from mean of -2.568 (range -10.8 to 0.878) to -0.484 (range -3.546 to 0.822). Weight z scores increased from mean of -1.412 (range -5.871 to 0.906) to -0.595 (range -2.178 to 0.926). CONCLUSIONS: In this case series, lipid limitation allowed normal growth while preventing the development of cholestasis and EFA deficiency.

Preservation of biochemical liver function with low-dose soy-based lipids in children with intestinal failure-associated liver disease.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. METHODS: The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. RESULTS: Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. CONCLUSIONS: Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.

Preventive effect of ursodeoxycholic acid on parenteral nutrition-associated liver disease in infants.

INTRODUCTION: Parenteral nutrition-associated cholestasis is well recognized phenomenon in the term and preterm infant receiving long-term parenteral nutrition. OBJECTIVES: The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) use on cholestasis in newborns on prolonged TPN. METHODS: A total of 56 infants were enrolled in this retrospective study: control group consisted of lower (1500 g) birth weight infants (n = 30), as well as the group of pediatric (n = 11) and surgical patients (n = 15) treated with UDCA. Blood chemistries were obtained two times weekly. RESULTS: All of 56 newborns developed cholestasis but duration of parenteral nutrition (PN) before onset of cholestasis was significantly longer in UDCA treated patients. Average duration of PN before the onset of cholestasis in control group of patients was 25 days in distinction from treated pediatric and surgical patients (39 and 34 days, respectively).The peak serum conjugated bilirubin (CB), AST, ALT and alkaline phosphatase (AP) levels were significantly lower in the treated groups.There was no significant difference among treated pediatric and surgical patients and between lower and higher birth weight infants considering the CB, ALT, AST and AP peak. Duration of cholestasis was significantly decreased in all treated groups.There was a significant difference in time needed to achieve complete enteral intake between pediatric and surgical patient group. CONCLUSION: Cholestasis developed significantly later in treated groups than in the controls. UDCA appears to be very successful in reducing the symptoms of cholestasis. The difference in efficacy of UDCA treatment between lower and higher birth weight infants could not be proven.

TPN cholestasis in infants: what do we know? Review.

Cholestasis is a condition in which there is a decrease in or complete cessation of bile flow. Total Parenteral Nutrition (TPN) Cholestasis cases have been on the rise due to the decrease ratio of mortality among premature babies. Using Pubmed, articles were searched using terms in combination: Molecular basis of cholestasis and management. The literature was also retrieved from books attributed to experts in the topic. This article describes the definition, incidence, risk factors, pathogenesis,the molecular basis of hepatobiliary transport, bile acid transporters,cellular regulation, and uptodate and prospective medical Care of TPN Cholestasis. It was found that TPN cholestasis in infants is considered as a major epidemic. Targeting Constitutive androstane receptor and Pregnane X receptor potent agonist will be one of the ultimate goals in inventing new pharmacological agents for the management and treatment of cholestasis related to TPN use. Glutamine, Omega 3 and soybean oil fat appear to have a protective role in the development of TPN cholestasis. However, further studies especially randomized control trials should be conducted.

Obstetric cholestasis (OC).

Obstetric cholestasis (OC) is the most common liver condition specific to pregnancy and affects around 5,000 women in the UK every year. It's generally benign for the mother although the main presenting symptom of pruritus can sometimes be so severe that the woman scratches herself until she bleeds. However, the main concerns are for the fetus, as the condition is associated with an increased risk of fetal distress, spontaneous premature labour and stillbirth. This article aims to provide information about the condition so that as a practising midwife you can offer women sufficient support should OC be suspected or diagnosed.

Cholestasis in neonates with red cell alloimmune hemolytic disease: incidence, risk factors and outcome.

BACKGROUND: Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been associated with iron overload due to intrauterine red cell transfusions (IUTs). Data on the incidence and severity of cholestasis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and outcome. OBJECTIVE: To evaluate incidence, risk factors, management and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease. METHODS: All (near-) term neonates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were included in this observational study. Liver function tests (including conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholestasis, investigated several potential risk factors and evaluated the management and outcome in affected neonates. RESULTS: A total of 313 infants with red cell alloimmune hemolytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70-19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05-20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy. CONCLUSION: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization.

Surgical intervention in the setting of parenteral nutrition-associated cholestasis may exacerbate liver injury.

PURPOSE: This study compares postoperative markers of liver injury in patients receiving intravenous fish oil (IFO) with parenteral nutrition (PN)-associated cholestasis (PNAC) to patients with resolved PNAC. METHODS: A retrospective review of all cholestatic-IFO patients undergoing abdominal laparotomy between March 1, 2007, and July 1, 2009, led to inclusion of 23 patients who collectively underwent 27 abdominal operations (13 pre-PNAC resolution and 14 post-PNAC resolution). Direct bilirubin (DB), total bilirubin, and alanine aminotransferase levels were examined over time in relation to operations. The time to resume presurgical trend of decreasing DB was calculated. RESULTS: Sixty-nine percent (9/13) of pre-PNAC resolution procedures were associated with postoperative increase in DB compared with 7% (1/14) of post-PNAC resolution procedures associated with a recurrence of cholestasis (P = .02; odds ratio, 29.3; 95% confidence interval, 2.79-306.8). The median time to return to the preoperative downward trend of DB was 21 days. CONCLUSIONS: Operations before PNAC resolution may be associated with an increased postoperative DB, possibly reflecting an exacerbation of liver injury. Operations post-PNAC resolution on IFO had a comparatively low incidence of postoperative cholestasis recurrence. Excepting clinical indication otherwise, it may be advisable to delay surgical intervention in the setting of PNAC in certain cases.

[Nutrition in cholestasis and long-term impact on trasnplant]. / Nutritia în colestaza si impactul pe termen lung dupa transplant.

AIM: Plurietiological hepatic cholestasis involves an increased risk of protein-caloric malnutrition and specifical nutritional deficiencies. Biological investigations to determine deficiencies in fat-soluble vitamins are essential for specific nutritional therapy . Although malnutrition is not an absolute contraindication for liver transplantation, its gravity has complex consequences in relation to this intervention. MATERIAL AND METHOD: The authors present a study conducted over a period of 5 years following the analysis of 293 children diagnosed with intra- or extrahepatic abnormalities that caused varying degrees of cholestasis. RESULTS: In the study group, the percentage of infants with cholestasis was 45.39% (133 cases) and among them 62.12% had malnutrition (82 children). Clinical evaluation of fat-soluble vitamins deficiency, in particular, but also of the soluble and minerals was performed in all patients. Liver transplantation was successfully performed in three cases. CONCLUSIONS: Most important factors affecting growth after transplantation were age at the time of the liver transplant and primary diagnosis that required transplant. The role of nutritional support prior to liver transplantation is of great importance. Quality nutritional support change impact that malnutrition has on survival after liver transplantation.

A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.

BACKGROUND: Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates. METHODS: During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing. RESULTS: Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect. CONCLUSIONS: Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).

Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management.

Here we report the reversal of cholestasis in 2 infants with intestinal failure and parenteral nutrition-associated liver disease. Treatment involved the substitution of a conventional intravenous fat emulsion with one containing primarily omega-3 fatty acids. Biochemical tests of liver function improved significantly. One child was removed from the liver transplantation list because of improved hepatic function, and the second child had complete resolution of cholestasis while solely on parenteral nutrition. This suggests that fat emulsions made from fish oils may be an effective means of treating and preventing this often-fatal condition. A randomized, controlled trial is necessary to study the efficacy of this new approach to parenteral nutrition-associated liver disease.

Liver abscess after transcatheter oily chemoembolization for hepatic tumors: incidence, predisposing factors, and clinical outcome.

PURPOSE: To evaluate the incidence of, predisposing factors for, and clinical outcome of liver abscess developing in patients with hepatic tumors after transcatheter oily chemoembolization (TOCE). MATERIALS AND METHODS: During the past 6-year period, 2,439 patients with hepatic tumors underwent a total of 6,255 TOCE procedures. With a retrospective review of medical records, the authors evaluated the occurrence of liver abscess, the statistical significance of potential predisposing factors including portal vein obstruction, metastatic tumors, biliary abnormalities (type 1, simple biliary obstruction; type 2, status prone to ascending biliary infection), malignant gastrointestinal mucosal lesions, and additional gelatin sponge particle embolization in liver abscess formation, and the clinical outcome of abscess. RESULTS: Fifteen liver abscesses occurred in 14 patients (0.2%). Liver abscesses developed in three of 987 (0.3%) TOCE procedures for portal vein obstruction, three of 114 (2.6%) procedures for metastatic tumors, one of 49 (1.8%) for type 1 biliary abnormality, four of 55 (7.4%) for type 2 biliary abnormality, two of 18 (11.1%) for malignant gastrointestinal mucosal lesion, and nine of 2,108 (0.4%) for additional gelatin sponge particle embolization. Univariate and multivariate statistical analysis showed that type 2 biliary abnormality was a significant predisposing factor. The mortality related to liver abscess occurred in two patients (13.3%). Thirteen liver abscesses were successfully treated with parenteral antibiotics and percutaneous catheter drainage. However, irreversible deterioration of liver function occurred in two patients. Two of nine further TOCE procedures in three patients caused recurrent septicemia and liver abscess. CONCLUSION: The biliary abnormality prone to ascending biliary infection was the most important predisposing factor to the development of liver abscess after TOCE. Postembolic liver abscess could be effectively managed with percutaneous catheter drainage.