The Evolution in Non-Alcoholic Fatty Liver Disease Patients' Profile and the Associated Sustainable Challenges: A Multidisciplinary Perspective.

The prevalence and incidence of NAFLD is rising due to the obesity pandemic, caused by the widespread availability of ultra-processed foods and the decrease of physical activity. Factors such as socioeconomic status (SES), ethnicity and geographical location are associated with NAFLD, with lower SES correlating with higher incidence, particularly in regions like America or Europe. Beside the quality of food, the quantity also plays a crucial role. The World Health Organization (WHO) recommends a Mediterranean diet with a balanced energy intake. Since no hard medical treatment is available for NAFLD, lifestyle adjustments are key. Patient empowerment by providing relevant information and co-ownership of the therapy will increase the implementation rate and enhance the quality of medical follow-up and medication adherence, as studies report a good adherence to medication among patients who are well-aware of the severity of their disease. Regarding sustainability, patients with NAFLD have a high load of ambulatory follow-up, which, since the COVID-19 pandemic, can be partially provided by teleconsulting. Both patients' lifestyle modifications and healthcare practitioners' therapeutical strategy can decrease the carbon footprint.

Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures.

Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN. IFALD pathogenesis is complex, depending on the TPN components as well as on the patient's medical conditions. Despite numerous animal studies and clinical observations, the molecular mechanisms driving IFALD remain largely unknown. The present study was set up to elucidate the mechanisms underlying IFALD. For this purpose, human liver spheroid co-cultures were treated with a TPN mixture, followed by RNA sequencing analysis. Subsequently, following exposure to TPN and its single nutritional components, several key events of liver injury, including mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, apoptosis, and lipid accumulation (steatosis), were studied using various techniques. It was found that prolonged exposure to TPN substantially changes the transcriptome profile of liver spheroids and affects multiple metabolic and signaling pathways contributing to liver injury. Moreover, TPN and its main components, especially lipid emulsion, induce changes in all key events measured and trigger steatosis.

Parenteral nutrition-associated liver injury: clinical relevance and mechanistic insights.

Intestinal failure-associated liver disease (IFALD) is a relatively common complication in individuals receiving parenteral nutrition (PN). IFALD can be manifested as different types of liver injury, including steatosis, cholestasis, and fibrosis, and could result in liver failure in some cases. The onset and progression of IFALD are highly dependent on various patient and PN-related risk factors. Despite still being under investigation, several mechanisms have been proposed. Liver injury can originate due to caloric overload, nutrient deficiency, and toxicity, as well as phytosterol content, and omega-6 to omega-3 fatty acids ratio contained in lipid emulsions. Additional mechanisms include immature or defective bile acid metabolism, acute heart failure, infections, and sepsis exerting negative effects via Toll-like receptor 4 and nuclear factor κB inflammatory signaling. Furthermore, lack of enteral feeding, gut dysbiosis, and altered enterohepatic circulation that affect the farnesoid x receptor-fibroblast growth factor 19 axis can also contribute to IFALD. Various best practices can be adopted to minimize the risk of developing IFALD, such as prevention and management of central line infections and sepsis, preservation of intestine's length, a switch to oral and enteral feeding, cyclic PN, avoidance of overfeeding and soybean oil-based lipid formulations, and avoiding hepatotoxic substances. The present review thus provides a comprehensive overview of all relevant aspects inherent to IFALD. Further research focused on clinical observations, translational models, and advanced toxicological knowledge frameworks is needed to gain more insight into the molecular pathogenesis of hepatotoxicity, reduce IFALD incidence, and encourage the safe use of PN.

Post-ICU nutrition: the neglected side of metabolic support.

PURPOSE OF THIS REVIEW: This review will focus on the neglected side of metabolic support in ICU survivors: nutritional therapy after critical illness. Knowledge of the evolution of the metabolism of patients that survived critical illness will be bundled, and current practices will be investigated. We will discuss some studies conducted to determine resting energy expenditure in ICU survivors and which identified barriers that cause interruptions in the feeding process based on published data between January 2022 and April 2023. RECENT FINDINGS: Resting energy expenditure can be measured using indirect calorimetry, as predictive equations have proven to fail in their attempt to have good correlations with measured values. No guidelines or recommendations are available on post-ICU follow-up, including screening, assessment, dosing, timing, and monitoring of (artificial) nutrition. A limited number of publications shared treatment adequacy between 64-82% for energy (calories) and 72-83% for protein intake in a post-ICU setting. Loss of appetite, depression, and oropharyngeal dysphagia are the most prominent physiological barriers responsible for decreased feeding adequacy. SUMMARY: Patients may be in a catabolic state during and after ICU discharge, with several factors impacting metabolism. Therefore, large prospective trials are needed to determine the physiological state of ICU survivors, determine nutritional requirements, and develop nutritional care protocols. Many barriers causing decreased feeding adequacy have already been identified, but solutions are scarce. This review depicts a variable metabolic rate among ICU survivors and a significant variation in feeding adequacy in-between world regions, institutions, and patient sub-phenotypes.

Parenteral Nutrition, Sepsis, Acute Heart Failure and Hepatotoxic Drugs Are Related to Liver Test Disturbances in Critically Ill Patients.

BACKGROUND: Parenteral nutrition (PN) is often associated with liver dysfunction in the ICU, although other factors such as sepsis, acute heart failure (AHF), and hepatotoxic drugs can be equally present. The relative impact of PN on liver dysfunction in critically ill patients is largely unknown. METHODS: We recorded the presence of pre-existing liver disturbances, AHF, sepsis, daily PN volume, and commonly used hepatotoxic drugs in adult ICU patients, together with daily aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkalic phosphatase (AP), total bilirubin (TB), and INR values in patients with three or more PN treatment days. A linear mixed-effects model was used to assess the relative contribution of each liver parameter. Nutritional adequacy was defined as intake/needs. RESULTS: We included 224 ICU patients with PN treatment lasting more than 3 days between 1 January 2017 and 31 December 2019. For AST, pre-existing liver disturbances (+180% ± 11%) and the presence of AHF (+75% ± 14%) were the main predictors of deterioration, whereas PN volume caused only a limited increase of 14% ± 1%/L. Similar results were observed for ALT. GGT, INR, and TB are mainly influenced by the presence of sepsis/septic shock and pre-existing liver disturbances, with no impact of PN or hepatotoxic drugs. Carbohydrate intake exceeded recommendations, and protein and lipid intake were insufficient in this study cohort. CONCLUSIONS: Liver test disturbances in ICU patients on PN are multifactorial, with sepsis and AHF having the highest influence, with only limited impact from PN and hepatotoxic drugs. Feeding adequacy can be improved.

Energy Guidance Using Indirect Calorimetry for Intestinal Failure Patients with Home Parenteral Nutrition: The Right Bag Right at the Start.

Intestinal failure is defined as the inability to absorb the minimum of macro and micronutrients, minerals and vitamins due to a reduction in gut function. In a subpopulation of patients with a dysfunctional gastrointestinal system, treatment with total or supplemental parenteral nutrition is required. The golden standard for the determination of energy expenditure is indirect calorimetry. This method enables an individualized nutritional treatment based on measurements instead of equations or body weight calculations. The possible use and advantages of this technology in a home PN setting need critical evaluation. For this narrative review, a bibliographic search is performed in PubMed and Web of Science using the following terms: 'indirect calorimetry', 'home parenteral nutrition', 'intestinal failure', 'parenteral nutrition', 'resting energy expenditure', 'energy expenditure' and 'science implementation'. The use of IC is widely embedded in the hospital setting but more research is necessary to investigate the role of IC in a home setting and especially in IF patients. It is important that scientific output is generated in order to improve patients' outcome and develop nutritional care paths.