Parenteral nutrition associated cholestasis

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 provides thus 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.

The aim of this study is to explore the risk factors for parenteral nutrition-associated liver disease (PNALD) in patients with severe acute pancreatitis by establishing a verification risk model.

A total of 176 patients with severe acute pancreatitis from January 2019 to August 2021, were assigned into the observation group (n = 88) and control group (n = 88) based on the diagnostic results of PNALD, randomly. Their clinical data were recorded. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and alkaline phosphatase (ALP), etc., were detected. The logistic model and desicion tree model were used to analyze the risk factors.

Patients in the observation group had higher levels of ALT, AST, TBIL, and lower level of ALP than those of control group (P < 0.05). Multivariate logistic regression analysis revealed that alcohol intake history, ALT ≥69.65 U/L, AST ≥71.27 U/L, TBIL ≥26.27 μmol/L and ALP ≤45.11 U/L were risk factors for PNALD. The levels of ALT and AST in observation group were two times as high as those in the control group, which conformed to the Danan's criteria and accorded with the results of univariate analysis.

The regression model showed high consistency with the decision tree model in the prediction of risk factors. Alcohol intake history, ALT ≥69.65 U/L, AST ≥71.27 U/L, TBIL ≥26.27 μmol/L and ALP ≤45.11 U/L are risk factors for PNALD.

While ursodeoxycholic acid is used in treating parenteral nutrition-associated cholestasis (PNAC) in neonates, its role in prevention is unclear.

In this systematic review and meta-analysis, we attempted to determine the role of ursodeoxycholic acid in preventing PNAC in neonates.

PubMed, Embase, Cochrane Library, Scopus, and CINAHL databases were searched on September 16, 2023, for interventional studies comparing ursodeoxycholic acid with placebo.

Of the 6180 unique records identified, five studies were eligible for inclusion (three randomised and two nonrandomised). Evidence from randomised trials showed that ursodeoxycholic acid prophylaxis did not reduce cholestasis, mortality, sepsis, and necrotising enterocolitis. Ursodeoxycholic acid prophylaxis reduced feed intolerance (RR 0.23 (0.09, 0.64); 1 RCT, 102 neonates), peak conjugated bilirubin levels (MD -0.13 (-0.22, -0.04) mg/dL; 1 RCT, 102 neonates), and time to full enteral feeds (MD -2.7 (-5.09, -0.31) days; 2 RCTs, 76 neonates). There was no decrease in hospital stay and parenteral nutrition duration. Data from nonrandomised studies did not show benefit in any of the outcomes. The certainty of the evidence was low to very low.

Because of the very low-quality evidence and lack of evidence on critical outcomes, definitive conclusions could not be made on using ursodeoxycholic acid to prevent parenteral nutrition-associated cholestasis in neonates.