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

Abstract

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.

Keywords: Intravenous lipid emulsions; Liver function tests; Parenteral nutrition; Phytosterolemia; Polymorphisms.