Genetic factors associated with alterations in liver function test results in adult hospitalized patients treated with parenteral nutrition: A substudy of a clinical trial.

OBJECTIVES: The presence of phytosterols in vegetable-based lipid emulsions has been associated with alterations in the results of liver function tests (LFTs). Serum levels of phytosterols are under strict genetic control. T-allele carriers in rs41360247 and C-allele carriers in rs4245791 of ABCG8genes are associated with higher phytosterolemia. The objective of this study was to determine the association between these single-nucleotide polymorphisms (SNPs) and LFT result alterations in an adult hospitalized population treated with parenteral nutrition. METHODS: This is a substudy of a previous clinical trial (EudraCT 2014-003597-17). It included adult hospitalized patients who had received at least 7 d of parenteral nutrition with 0.8 g/kg/d of an olive/soybean lipid emulsion, randomized 1:1 to receive the same olive/soybean emulsion or 100% fish oil at a dose of 0.4 g/kg/d for 7 d. Plasma phytosterols and their fractions, rs41360247 and rs4245791 of ABCG8 genes, and LFT were determined. Analyses of variance were performed to determine the association between the SNPs and LFT values, as well as total phytosterol values and their fractions. Simple linear regressions were performed to analyze LFT variations and the different interactions of the SNPs studied with phytosterols and their fractions. Interactions of the synergic variable plasma phytosterol and its fractions with SNPs allow us to study the interaction of the SNPs with phytosterols with a regression. RESULTS: We included 19 participants. In the multivariate model, total phytosterols, sitosterol, and lanosterol were positively associated with increases in γ-glutamyltransferase. Significant increases with stigmasterol were associated with the T allele of rs41360247, whereas campesterol showed only a tendency to increase that was not significant. Increases in alkaline phosphatase were associated with T-rs41360247 independent of the presence of phytosterols. With stigmasterol, C-allele carriers of rs4245791 showed a tendency to increase, and also for sitosterol and lanosterol, although independent of the SNP analyzed. Increases in alanine aminotransferase were positively associated with total phytosterol and sitostanol, whereas lanosterol and stigmasterol were associated with the presence of the T allele of rs41360247. CONCLUSIONS: With both SNPs rs41360247 and rs4245791, the alteration in parameters of liver function in adult patients with short-term parenteral nutrition is conditional.

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients.

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.

Phytosterolaemia associated with parenteral nutrition administration in adult patients.

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) µg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

Phytosterolemia and γ-glutamyl transferase in adults with parenteral nutrition: Fish versus vegetal lipids: A randomized clinical trial.

OBJECTIVES: Fish oil (FO)-based lipid emulsions (LEs) have been reported to prevent hepatic dysfunction in patients treated with parenteral nutrition (PN). We studied patients with alterations of γ-glutamyl transferase (GGT) associated with the administration of PN containing olive/soybean (O/S)-based LE. The aim of this study was to determine whether the strategy of reducing the lipid dose by 50%, by changing to an FO-based LE, reduced plasma levels of phytosterols (PS) and GGT more effectively and safely, than the strategy of reducing lipid contribution by 50% while maintaining the same LE composition. METHODS: A randomized double-blind clinical trial was carried out in patients with normal initial GGT, who after a minimum of 1 wk of daily PN (0.8 g/kg of O/S-based LE) presented with GGT values twice the upper normal value. At the time of randomization 1:1, lipids were reduced to 0.4 g/kg daily. Group A maintained O/S LE and group B changed to FO LE. The primary endpoints were reduction of plasmatic PS and GGT on day 7 after randomization, performed in the study population per protocol by Student's t test and simple linear regression. Secondary outcomes included alkaline phosphatase (AP), alanine transaminase (ALT), and total bilirubin (BIL), and safety variables. RESULTS: Nineteen patients were included. On day 7 after randomization, GGT and AP values were higher in the O/S group (n = 10; GGT: median [Med], 4.99; interquartile range [IQR], 4.09; AP: Med, 2.59 µkat/L; IQR 1.74) than in the FO group (n = 9; GGT: Med, 2.26 µkat/L; IQR, 1.07; AP: Med, 1.2 µkat/L; IQR 1.44). Although there were no differences in ALT and BIL values, the ALT decrease was larger and more statistically significant in the FO group than in the O/S group (P = 0.009). Total PS (Med, 21.10 µg/mL; IQR, 5.50) in the O/S group was higher than in the FO group (Med, 13.4 µg/mL; IQR, 10.65; P = 0.002). Significant decreases in PS and their fractions were observed, with the exception of campesterol and stigmasterol. CONCLUSION: Plasma accumulation of PS and high values of GGT, AP, and ALT can be prevented with the exclusive administration of FO-based LE.

Risk factors of hepatic function alterations in hospitalized adult patients treated with short-term parenteral nutrition receiving the same lipid composition at the same dose.

BACKGROUND: High doses and vegetable origin of lipid emulsions (LE) are prominent factors for liver test (LT) alterations in patients treated with parenteral nutrition (PN). This study aims to determine incidence of LT alterations, and risk factors related to these alterations in patients with short term PN with homogenous LE. METHODS: Adult non-critically ill hospitalized patients, with normal LTs at the beginning of PN, receiving 0.8 g/kg/day of an olive/soybean LE were included. A paired Student t-test was applied to compare final with initial LT values. LT variation (end vs start of PN) according to type of surgery and infection was studied by means of an analysis of the variance. Univariate and multivariate analyses were constructed to relate the variations of each of the 4 LTs with the adjustment variables. RESULTS: One hundred eighty one patients (66.57 ± 12.89 years; 72.4% men), 66.8% suffered from cancer. Final LT values increased from initial values for gamma-glutamyltransferase (GGT) 2.69 ± 2.49 µkat/L vs 0.55 ± 0.36 µkat/L, alkaline phosphatase (AP) 1.97 ± 1.49 µkat/L vs 1.04 ± 0.33 µkat/L, and alanine aminotransferase (ALT) 0.57 ± 0.92 µkat/L vs 0.32 ± 0.26 µkat/L. GGT and AP variations were associated with days of PN; GGT, AP and total bilirubin with surgical patients, AP variations with infection, and GGT with cancer. Multivariate analysis: elevation of GGT, AP and ALT was related to infection, days of PN and surgery. CONCLUSIONS: Factors that increased the risk of LTs elevation during short term PN treatment were duration of PN, surgery, cancer, and infection associated with oxidative stress.