Comparison of two formulations of intravenous lipid emulsions in pediatric intestinal failure.

PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.

Inflammation drives pathogenesis of early intestinal failure-associated liver disease.

Patients with intestinal failure who receive long-term parenteral nutrition (PN) often develop intestinal failure-associated liver disease (IFALD). Although there are identified risk factors, the early pathogenesis is poorly understood and treatment options are limited. Here, we perform a transcriptomic analysis of liver tissue in a large animal IFALD model to generate mechanistic insights and identify therapeutic targets. Preterm Yorkshire piglets were provided PN or bottle-fed with sow-milk replacer for 14 days. Compared to bottle-fed controls, piglets receiving PN developed biochemical cholestasis by day of life 15 (total bilirubin 0.2 vs. 2.9 mg/dL, P = 0.01). RNA-Seq of liver tissue was performed. Ingenuity Pathway Analysis identified 747 differentially expressed genes (343 upregulated and 404 downregulated) with an adjusted P < 0.05 and a fold-change of > |1|. Enriched canonical pathways were identified, demonstrating broad activation of inflammatory pathways and inhibition of cell cycle progression. Potential therapeutics including infliximab, glucocorticoids, statins, and obeticholic acid were identified as predicted upstream master regulators that may reverse the PN-induced gene dysregulation. The early driver of IFALD in neonates may be inflammation with an immature liver; identified therapeutics that target the inflammatory response in the liver should be investigated as potential treatments.

Dysregulation of the Skin-Liver Axis in Prurigo Nodularis: An Integrated Genomic, Transcriptomic, and Population-Based Analysis.

Pruritus has long been linked to hepatic dysfunction; however, there are limited data characterizing the association between liver disease and prurigo nodularis (PN), a chronic inflammatory skin disease featuring severe pruritis. We thus conducted a cross-sectional analysis of hepatic comorbidities in PN patients using TriNetX, a large global health research network. This analysis revealed that PN patients had a higher risk (p < 0.001) of developing liver cirrhosis, acute and subacute hepatic failure, inflammatory liver disease, chronic hepatitis, nonalcoholic steatohepatitis, portal hypertension, fatty liver, chronic passive congestion of the liver, and hepatocellular carcinoma compared with healthy controls. The cumulative incidence of liver disease was about three times higher in PN patients compared with healthy controls. These findings provided the basis for translational studies to investigate a genetic mechanism for this association. Cutaneous transcriptomic analysis performed on PN patients revealed the dysregulation of genes related to hepatic failure in lesional PN compared with both nonlesional PN and control skin. Similarly, gene set variation analysis (GSVA) revealed a significantly increased (p < 0.05) activation of liver metabolism, chronic hepatic failure, acute hepatic failure, cholestatic liver disease, polycystic liver disease, and hepatocellular carcinoma pathways in lesional PN compared with control skin. A subsequent genome-wide association study (GWAS) identified shared single-nucleotide polymorphisms (SNPs) in the genes AR, EDIL3, MACROD2, PCSK5, RUNX1T1, TENM4, and ZEB2 between PN and liver disease from the FinnGen cohort. Significant dysregulation of the skin-liver axis in PN patients may explain the increased incidence and severity of hepatic comorbidities and help identify future therapeutic targets for PN.

[Liver failure caused by recurrent biliary bleeding associated with Osler's disease: a case report].

A 34-year-old female patient with epigastric pain was admitted to our hospital. She reported an underlying condition of Rendu-Osler-Weber disease and a history of coil embolization for pulmonary arteriovenous fistula. A blood test revealed high hepatobiliary enzyme levels. An abdominal contrast-enhanced computed tomography revealed numerous arterioportal and arteriovenous shunts in the liver and a high-density area in the bile duct, which was diagnosed as biliary bleeding. She underwent transpapillary biliary drainage by endoscopic retrograde cholangiopancreatography, but recurrent biliary bleeding caused cholangitis, which was complicated by multiple liver abscesses. She was awaiting her turn for liver transplantation from brain-dead donors, but the liver abscesses were difficult to improve. Further, liver failure, septic pulmonary embolism, and disseminated intravascular coagulation were complicated. Thus, recurrent further biliary bleeding resulted in hemorrhagic shock, which required frequent blood transfusions. Furthermore, the continuous abscess to the intrahepatic bile duct in the anterior superior segment penetrated her diaphragm, causing hemothorax and eventually, death. Establishing progressive treatment, including liver transplantation, is considered necessary for this intractable disease.

Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease.

OBJECTIVES: The prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association. METHODS: The study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death. RESULTS: During a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84-0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; Pinteraction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (Pinteraction = 0.216). CONCLUSIONS: Lower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.

Fatal acute portal vein thrombosis associated with hepatic cysts in a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) often involves polycystic liver disease (PLD). In severe cases, PLD can develop various complications. However, fatal acute portal vein thrombosis (APVT) associated with PLD has not been reported. A 64-year-old male reported mild consciousness disorder. He had been under maintenance hemodialysis for end-stage renal disease due to ADPKD with PLD. Because of recurring hepatic cyst infections, he had sustained high levels of C-reactive protein. Regarding the mild consciousness disorder, a diagnosis of hepatic encephalopathy was made based on an elevation of serum ammonia without any other abnormal liver function tests. Several days after his admission, hepatobiliary enzymes elevated, and acute liver failure progressed. Enhanced abdominal computed tomography suggested the possibility of complete occlusion of the portal vein by a thrombus. Based on an absence of obvious portosystemic collaterals, a diagnosis of APVT was made. The patient died 19 days after admission. Patients with PLD with repeated cystic infections have been seen to develop liver failure, and APVT formation may be one cause of the rapid progression of fatal liver failure. In conclusion, this is the first paper to report on the involvement of APVT in patients with PLD.

Kidney Dysfunction in the Setting of Liver Failure: Core Curriculum 2024.

Individuals with liver disease are susceptible to pathophysiological derangements that lead to kidney dysfunction. Patients with advanced cirrhosis and acute liver failure (ALF) are at risk of developing acute kidney injury (AKI). Hepatorenal syndrome type 1 (HRS-1, also called HRS-AKI) constitutes a form of AKI unique to the state of cirrhosis and portal hypertension. Although HRS-1 is a condition primarily characterized by marked renal vasoconstriction and kidney hypoperfusion, other pathogenic processes, such as acute tubular injury and renal vein congestion, can overlap and further complicate the course of HRS-1. ALF can lead to AKI through mechanisms that involve systemic inflammation, direct drug toxicity, or bile acid-induced tubulopathy. In addition, the growing prevalence of nonalcoholic steatohepatitis is changing the spectrum of chronic kidney disease in cirrhosis. In this installment of AJKD's Core Curriculum in Nephrology, we explore the underpinnings of how cirrhosis, ALF, acute cholestasis, and post-liver transplantation can be associated with various forms of acute, subacute, or chronic kidney diseases. We navigate through the recommended therapies for each condition, including supportive care, pharmacological interventions, kidney replacement therapy, and organ transplantation. Finally, key acid-base and electrolyte disorders associated with hepatobiliary disease are also summarized.

The challenges and potential in developing microRNA associated with regeneration as biomarkers to improve prognostication for liver failure syndromes and hepatocellular carcinoma.

INTRODUCTION: Determining the need for liver transplantation remains critical in the management of hepatocellular carcinoma (HCC) and liver failure syndromes (including acute liver failure and decompensated cirrhosis states). Conventional prognostic models utilize biomarkers of liver and non-liver failure and have limitations in their application. Novel biomarkers which predict regeneration may fulfil this niche. microRNA are implicated in health and disease and are present in abundance in the circulation. Despite this, they have not translated into mainstream clinical biomarkers. AREAS COVERED: We will discuss current challenges in the prognostication of patients with liver failure syndromes as well as for patients with HCC. We will discuss biomarkers implicated with liver regeneration. We then provide an overview of the challenges in developing microRNA into clinically tractable biomarkers. Finally, we will provide a scoping review of microRNA which may have potential as prognostic biomarkers in liver failure syndromes and HCC. EXPERT OPINION: Novel biomarkers are needed to improve prognostic models in liver failure syndromes and HCC. Biomarkers associated with liver regeneration are currently lacking and may fulfil this niche. microRNA have the potential to be developed into clinically tractable biomarkers but a consensus on standardizing methodology and reporting is required prior to large-scale studies.

[An anatomical case of obstructive jaundice due to the rapid enlargement of hepatic peribiliary cysts in end-stage alcoholic liver cirrhosis].

A man in his 60s had end-stage alcoholic cirrhosis. About six months before his death, hepatic peribiliary cysts (HPBC) rapidly increased, and he developed jaundice and liver failure. The pathological autopsy performed after his death revealed that his intrahepatic bile duct was pressured due to multiple cysts caused by HPBC, which resulted in liver failure. Some cases of HPBC have been associated with alcoholic cirrhosis;however, no other cases of increased HPBC in a short period of time have been reported. Although identifying the cause of increased HPBC in a short time is difficult in this case, it may be have been caused by continuous alcohol drinking after the onset of HPBC. Most patients with HPBC have liver cirrhosis and obstructive jaundice that may promote liver failure as in this case. Therefore, patients with HPBC should not only be instructed for abstinence but also promptly consider effective treatments in the event of obstructive jaundice to prevent liver dysfunction.

[Systematic analysis of liver failure accompanied with hemophagocytic syndrome in adults].

Objective: To retrospectively analyze literature reports and summarize the clinical characteristics of liver failure in patients accompanied with adult hemophagocytic syndrome (HPS). Methods: The Wanfang, CNKI, VIP, PubMed, and Ovid databases were searched for relevant literature on liver failure patients accompanied with adult HPS published from January 1980 to May 2022. The final included literature was systematically reviewed after screening. Results: There were a total of 77 liver failure cases accompanied with adult HPS, with an average age of (41.8 ± 12.5) years. The most common clinical manifestations of these cases were persistent high fever, fatigue, gastrointestinal symptoms, and severe jaundice. The imaging changes were not specific, and the most common was hepatosplenomegaly. Laboratory examination showed a significant increase in serum total bilirubin, lactate dehydrogenase, triglycerides, and soluble interleukin-2 receptor levels, as well as serum ferritin, while there was a decrease in prothrombin activity, natural killer cell activity, and hemocytopenia of two or more lineages in peripheral blood. Myelogram examination showed hemophagocytosis. Adult HPS secondary to infection was more likely to be accompanied with liver failure (55.8%), with an overall case fatality rate of 84.4%. Conclusion: Patients with liver failure accompanied with adult HPS have an extremely high mortality rate and a poor prognosis. Early diagnosis and treatment are the keys to improving the prognosis.

Scrub typus fulminating as liver failure: A rare report.

Scrub typhus is almost an endemic tropical mite-borne, zoonotic illness often cognate with the bacterium Orientia tsutsugamushi. After a typical incubation period of a fortnight, non-specific symptoms including fever, headache, and a specific skin 'eschar' is customary. If untreated after a symptomatic week, scrub typus may precipitate end-organ involvements spiraling into vivid complications. Nevertheless, crub typhus tends to display mild transaminitis, frank liver failure is hardly common in clinical practice. An instance of scrub typus triggering fulminant hepatic failure (FHF) in a middle-aged female is being reported here.

Clinical characteristics of 1279 patients with hepatitis E in Tianjin.

Hepatitis E virus infection is a major cause of acute hepatitis, typically self-limiting but occasionally leading to liver failure. Understanding disease progression factors could inform prevention strategies. This study aimed to analyse the characteristics of a large cohort of hospitalised hepatitis E patients in Tianjin, China, and explore factors influencing their progression to liver failure. A total of 1279 hospitalised patients with hepatitis E were included in this cross-sectional study in Tianjin, China. Student's t-test and the Mann-Whitney U-test were used for comparisons. Multiple logistic regression analysis was used to explore the association. Among these 1279 patients, 107 (8.4%) developed liver failure. Patients with diabetes mellitus (DM) (95% confidence interval [CI] 1.150-2.887, p = 0.011), liver cirrhosis (95% [CI] 2.229-7.224, p < 0.001), and hepatitis B (95% [CI] 1.159-4.512, p = 0.017) were more likely to progress to liver failure. Hepatitis E patients with comorbid DM, liver cirrhosis, or hepatitis B virus co-infection have higher risks of developing liver failure. Hepatitis E vaccination may be recommended for these vulnerable patients to curb disease severity.

The gut microbiome and intestinal failure-associated liver disease.

Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.

The Hepatic Nerves Regulated Inflammatory Effect in the Process of Liver Injury: Is Nerve the Key Treating Target for Liver Inflammation?

Liver injury is a common pathological basis for various liver diseases. Chronic liver injury is often an important initiating factor in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, hepatitis A and E infections are the most common causes of acute liver injury worldwide, whereas drug toxicity (paracetamol overdose) in the USA and part of Western Europe. In recent years, chronic liver injury has become a common disease that harms human health. Meanwhile, the main causes of chronic liver injury are viral hepatitis (B, C) and long-term alcohol consumption worldwide. During the process of liver injury, massive inflammatory cytokines are stimulated by these hazardous factors, leading to a systemic inflammatory response syndrome, followed by a compensatory anti-inflammatory response, which causes immune cell dysfunction and sepsis, subsequent multi-organ failure. Cytokine release and immune cell infiltration-mediated aseptic inflammation are the most important features of the pathobiology of liver failure. From this perspective, diminishing the onset and progression of liver inflammation is of clinical importance in the treatment of liver injury. Although many studies have hinted at the critical role of nerves in regulating inflammation, there largely remains undetermined how hepatic nerves mediate immune inflammation and how the inflammatory factors released by these nerves are involved in the process of liver injury. Therefore, the purpose of this article is to summarize previous studies in the field related to hepatic nerve and inflammation as well as future perspectives on the aforementioned questions. Our findings were presented in three aspects: types of nerve distribution in the liver, how these nerves regulate immunity, and the role of liver nerves in hepatitis and liver failure.

Abnormal distribution of fat tissue and its association with intestinal failure-associated liver disease in children and adolescents with long-time parenteral nutrition support: A case-control study.

BACKGROUND: Patients with intestinal failure (IF) often present with abnormal body composition characterized by high fat mass. However, the distribution of fat and its association with the development of IF-associated liver disease (IFALD) remain unclear. This study aims to investigate the body composition and its relationship with IFALD in older children and adolescents with IF. METHODS: This retrospective case-control study enrolled patients with IF receiving parenteral nutrition (PN) at Keio University Hospital who initiated PN before the age of 20 years (cases). The control group included patients with abdominal pain, with available computed tomography (CT) scan and anthropometric data. CT scan images of the third lumbar vertebra (L3) were used for body composition analysis and compared between the groups. Liver histology was compared with CT scan findings in IF patients who underwent biopsy. RESULTS: Nineteen IF patients and 124 control patients were included. To account for age distribution, 51 control patients were selected. The median skeletal muscle index was 33.9 (29.1-37.3) in the IF group and 42.1 (39.1-45.7) in the control group (P < 0.01). The median visceral adipose tissue index (VATI) was 9.6 (4.9-21.0) in the IF group and 4.6 (3.0-8.3) in the control group (P = 0.018). Among the 13 patients with IF who underwent liver biopsies, 11 (84.6%) had steatosis, and there was a tendency for fibrosis to correlate with VATI. CONCLUSION: Patients with IF exhibit low skeletal muscle mass and high visceral fat, which may be related to liver fibrosis. Routine monitoring of body composition is recommended.

Deconvolution of the fluorescence spectra measured through a needle probe to assess the functional state of the liver.

OBJECTIVES: Currently, one of the most pressing issues for surgeons in the treatment of obstructive jaundice is the ability to assess the functional state of the liver and to detect and determine the degree of liver failure in a timely manner with simple and objective techniques. In this regard, the use of fluorescence spectroscopy method can be considered as one of the ways to improve the informativity of existing diagnostic algorithms in clinical practice and to introduce new diagnostic tools. Thus, the aim of the work was to study in vivo the functional state of liver parenchyma by the method of fluorescence spectroscopy implemented through a needle probe and assess the contribution of the main tissue fluorophores to reveal new diagnostic criteria. MATERIALS AND METHODS: We compared data from 20 patients diagnosed with obstructive jaundice and 11 patients without this syndrome. Measurements were performed using a fluorescence spectroscopy method at excitation wavelengths of 365 and 450 nm. Data were collected using a 1 mm fiber optic needle probe. The analysis was based on the comparison of the results of deconvolution with the combinations of Gaussian curves reflecting the contribution of the pure fluorophores in the liver tissues. RESULTS: The results showed a statistically significant increase in the contribution of curves reflecting NAD(P)H fluorescence, bilirubin, and flavins in the group of patients with obstructive jaundice. This and the calculated redox ratio values indicated that the energy metabolism of the hepatocytes may have shifted to glycolysis due to hypoxia. An increase in vitamin A fluorescence was also observed. It may also serve as a marker of liver damage, indicating impaired vitamin A mobilization from the liver due to cholestasis. CONCLUSIONS: The results obtained reflect changes associated with shifts in the content of the main fluorophores characterizing hepatocyte dysfunction caused by accumulation of bilirubin and bile acids and after disturbance of oxygen utilization. The contributions of NAD(P)H, flavins, and bilirubin as well as vitamin A can be used for further studies as promising diagnostic and prognostic markers for the course of liver failure. Further work will include collecting fluorescence spectroscopy data in patients with different clinical effects of obstructive jaundice on postoperative clinical outcome after biliary decompression.

Study of the Relationship Between Liver Function Markers and Traumatic Rhabdomyolysis: A Retrospective Study of Hemorrhagic Patients Admitted to Intensive Care Unit in a Level I Trauma Center.

BACKGROUND: Traumatic rhabdomyolysis (RM) is common and contributes to the development of medical complications, of which acute renal failure is the best described. Some authors have described an association between elevated aminotransferases and RM, suggesting the possibility of associated liver damage. Our study aims to evaluate the relationship between liver function and RM in hemorrhagic trauma patients. METHODS: This is a retrospective observational study conducted in a level 1 trauma center analyzing 272 severely injured patients transfused within 24 hours and admitted to intensive care unit (ICU) from January 2015 to June 2021. Patients with significant direct liver injury (abdominal Abbreviated Injury Score [AIS] >3) were excluded. Clinical and laboratory data were reviewed, and groups were stratified according to the presence of intense RM (creatine kinase [CK] >5000 U/L). Liver failure was defined by a prothrombin time (PT)-ratio <50% and an alanine transferase (ALT) >500 U/L simultaneously. Correlation analysis was performed using Pearson's or Spearman's coefficient depending on the distribution after log transformation to evaluate the association between serum CK and biological markers of hepatic function. Risk factors for the development of liver failure were defined with a stepwise logistic regression analysis of all relevant explanatory factors significantly associated with the bivariate analysis. RESULTS: RM (CK >1000 U/L) was highly prevalent in the global cohort (58.1%), and 55 (23.2%) patients presented with intense RM. We found a significant positive correlation between RM biomarkers (CK and myoglobin) and liver biomarkers (aspartate transferase [AST], ALT, and bilirubin). Log-CK was positively correlated with log-AST (r = 0.625, P < .001) and log-ALT (r = 0.507, P < .001) and minimally with log-bilirubin (r = 0.262, P < .001). Intensive care unit stays were longer for intense RM patients (7 [4-18] days vs 4 [2-11] days, P < .001). These patients required increased renal replacement therapy use (4.1% vs 20.0%, P < .001) and transfusion requirements. Liver failure was more common (4.6% vs 18.2%, P < .001) for intense RM patients. It was associated with bivariate and multivariable analysis with intense RM (odds ratio [OR], 4.51 [1.11-19.2]; P = .034), need for renal replacement therapy, and Sepsis-Related Organ Failure Assessment Score (SOFA) score on day 1. CONCLUSIONS: Our study established the presence of an association between trauma-related RM and classical hepatic biomarkers. Liver failure was associated with the presence of intense RM in bivariate and multivariable analysis. Traumatic RM could have a role in the development of other system failures, specifically at the hepatic level, in addition to the already known and well-described renal failure.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Lipid strategies to prevent intestinal failure-associated liver disease in neonates: A pilot trial.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) occurs in up to 50% of neonates treated with prolonged parenteral nutrition. Preventative strategies for IFALD include soybean oil lipid emulsion (SOLE) minimization and use of mixed-oil intravenous lipid emulsions (ILE). We conducted a pilot study prospectively comparing these two ILE strategies in the prevention of IFALD in neonates who required abdominal surgery. METHODS: We randomized eligible neonates to SOLE at 1 g/kg/day (SOLE Min) or mixed-oil ILE containing fish oil (MOLE) at 3 g/kg/day. These treatment groups were also compared with historic controls who received SOLE at 2-3 g/kg/day (SOLE Historic). We defined IFALD as a direct bilirubin >2 mg/dl on two measurements. Secondary outcomes included laboratory, growth, clinical, and nutrition outcomes. RESULTS: A total of 24 prospective and 24 historic patients were included. There was no difference in the rate of IFALD. However, there was a difference in the weekly change of direct bilirubin levels (SOLE Historic +0.293 mg/dl/week vs MOLE, P < 0.001; SOLE Min +0.242 mg/dl/week vs MOLE, P < 0.001). The MOLE group also had a lower direct bilirubin at study completion (SOLE Historic, 1.7 ± 1.7 mg/dl; SOLE Min, 1.6 ± 1.4 mg/dl; MOLE, 0.4 ± 0.4 mg/dl; P = 0.002) and received greater total calories (P = 0.008). CONCLUSION: The rate of IFALD did not differ when comparing ILE strategies in neonates requiring abdominal surgery. However, the MOLE group maintained significantly lower direct bilirubin levels over time while receiving increased calories. This pilot study highlights the need for further randomized controlled trials comparing these ILE strategies.

Cellular Pathogenesis of Hepatic Encephalopathy: An Update.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome derived from metabolic disorders due to various liver failures. Clinically, HE is characterized by hyperammonemia, EEG abnormalities, and different degrees of disturbance in sensory, motor, and cognitive functions. The molecular mechanism of HE has not been fully elucidated, although it is generally accepted that HE occurs under the influence of miscellaneous factors, especially the synergistic effect of toxin accumulation and severe metabolism disturbance. This review summarizes the recently discovered cellular mechanisms involved in the pathogenesis of HE. Among the existing hypotheses, ammonia poisoning and the subsequent oxidative/nitrosative stress remain the mainstream theories, and reducing blood ammonia is thus the main strategy for the treatment of HE. Other pathological mechanisms mainly include manganese toxicity, autophagy inhibition, mitochondrial damage, inflammation, and senescence, proposing new avenues for future therapeutic interventions.