Fat emulsion is an indispensable component of total parenteral nutrient (PN) preparations. Fat emulsions provide essential fatty acids and play an important role as an energy source. Furthermore, lipids are involved in the structure and function of cell membranes and receptors, gene expression modification, and inflammatory and immune response modification [
We searched both electronically and manually for journal articles published from January 2007 to March 2017. We searched PubMed, the Cochrane Library, Web of Science, EMBASE, and the Chinese Biomedicine Database using the following search terms: (structured triglyceride OR structured triacylglycerol OR structured lipid OR STG) AND (long-chain triglyceride OR long-chain triacylglycerol OR long-chain lipid OR medium-chain triglyceride OR medium-chain triacylglycerol OR medium-chain lipid OR MCT OR LCT OR MCT/LCT) AND (randomized controlled trial OR RCT). No language restriction was applied and the search was performed by two independent researchers (Figure
The included studies met the following criteria: (1) the study compared STG emulsion with MCT/LCT mixture; (2) the study population consisted of patients with benign or malignant liver tumors who had undergone elective liver surgery; (3) the study was the latest publication (if the same data had been published multiple times); and (4) the study was a randomized controlled trial (RCT).
The following studies were excluded: (1) the PN type or the details of the surgical method were not reported; (2) the patients had not undergone liver surgery or had severe chronic liver disease (and were staying in an ICU); (3) there was no comparison of STG emulsion with MCT/LCT mixture; (4) the study outcomes did not include postoperative liver or immune function indicators; (5) the study was a report of data used in a later study; (6) low-quality studies: the quality of RCTs was evaluated based on the Jadad scale system: if the total score was <4, the RCT was deemed to be of low quality; (7) abstracts, case reports, letters, comments, and reviews without original data, and studies that presented insufficient data were not included; and (8) studies that were not RCTs were not included.
All reports found during the literature search were screened by two independent investigators. When the two authors had a disagreement, they first tried to resolve it through discussion. If this failed, the final decision was made by a third author. EndNote reference management software was used to search for and remove any duplicate studies.
The following data were independently extracted by the two investigators and checked by the other authors: title; authors; year of publication; country; study design; PN type; number of patients (by age and sex); postoperative liver function markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, prealbumin, and total bilirubin; and postoperative immune function markers such as immunoglobulins A, M, and G (IgA, IgM, and IgG) and CD3+, CD4+, and CD8+ cell counts.
RevMan (version 5.3.0) software provided by the Cochrane Collaboration was used to perform the meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Odds ratios (ORs) were used for the analyses of dichotomous variables and 95% confidence intervals (CIs) were reported. The Mantel-Haenszel, chi-square, and
On the basis of the inclusion and exclusion criteria, six RCTs were included in the meta-analysis. The total number of patients was 516, of whom 259 were in the STG group and 257 were in the LCT/MCT group. The detailed characteristics of all the included studies are shown in Table
The characteristics of all the included studies.
Author | Year | Country | Study type | Group | Patients number | Male/female | Age, |
Study quality |
---|---|---|---|---|---|---|---|---|
Peng et al. [ |
2017 | China | RCT | STG | 50 | 33/17 | 52.1 ± 8.5 | 7 |
MCT/LCT | 50 | 30/20 | 51.3 ± 3.2 | |||||
Shi et al. [ |
2015 | China | RCT | STG | 40 | 25/15 | 56 ± 10 | 5 |
MCT/LCT | 40 | 26/14 | 57 ± 11 | |||||
Wu et al. [ |
2013 | China | RCT | STG | 33 | 25/8 | 49.1 ± 1.8 | 7 |
MCT/LCT | 33 | 25/8 | 51.3 ± 3.2 | |||||
Zhou et al. [ |
2011 | China | RCT | STG | 29 | 24/5 | 53.83 ± 10.29 | 7 |
MCT/LCT | 30 | 23/7 | 52.37 ± 12.27 | |||||
Jing et al. [ |
2010 | China | RCT | STG | 64 | 47/17 | 49.9 ± 8.6 | 5 |
MCT/LCT | 61 | 45/16 | 48.7 ± 10.5 | |||||
Zhuo and Qi [ |
2010 | China | RCT | STG | 43 | 25/18 | 43.0 ± 5.0 | 7 |
MCT/LCT | 43 | 27/16 | 45.0 ± 8.0 |
RCT = randomized controlled trial; STG: structured triglycerides; MCT/LCT: medium- and long-chain triglycerides.
Meta-analysis of postoperative ALT.
Meta-analysis of postoperative AST.
Meta-analysis of postoperative ALB.
Meta-analysis of postoperative prealbumin.
Meta-analysis of postoperative total bilirubin.
Two included studies reported the postoperative immune function. The results of meta-analysis show that there is a clear difference between the STG and MCT/LCT groups in terms of postoperative immunoglobulins M and G [IgM (OR = 1.36; 95% CI, 0.91–1.81;
Meta-analysis of postoperative IgA.
Meta-analysis of postoperative IgM.
Meta-analysis of postoperative IgG.
Meta-analysis of the postoperative CD3+ cell counts.
Meta-analysis of the postoperative CD4+ cell counts.
Meta-analysis of the postoperative CD8+ cell counts.
Funnel plots were constructed to assess the publication bias in this meta-analysis. As shown in Figure
Funnel plots: (a) ALT; (b) AST; (c) albumin; (d) prealbumin; (e) total bilirubin; (f) IgA; (g) IgM; (h) IgG; (i) CD3+; (j) CD4+; (k) CD8+.
Dietary lipids are important factors that affect xenobiotic metabolism. Hepatic microsomal cytochrome P450 plays a key role in the metabolism of various endogenous and exogenous compounds. Consequently, total PN (which includes lipids) may be associated with liver disease, which frequently occurs in neonates and in patients with liver disease.
STG emulsions are an alternative to physical MCT/LCT mixtures. STG emulsions can be manufactured by mixing MCT and LCT oils and heating the mixture in the presence of a catalyst. A number of pathologic changes leading to the development of hepatic dysfunction have been observed in PN patients [
The main results of the present study showed that STG emulsions have no effect on hepatocellular integrity, whereas both physical MCT/LCT mixtures cause subclinical hepatic injury in postoperative patients [
SGT emulsions did not increase the burden on the liver and they were beneficial in terms of inhibiting protein decomposition, reducing tissue consumption, and improving the metabolism of human body protein. This may be related to the relatively stable nature of STGs. STG emulsions did not increase the rate of cholestasis and they led to benefits in terms of decreasing the levels of postoperative total bilirubin. Total bilirubin can reflect postoperative liver function and biliary obstruction. Sandstrom and colleagues [
The meta-analysis results also showed that there was a clear difference between the STG and MCT/LCT groups in terms of postoperative immune function. IgG, IgA, and IgM levels are common indicators that can reflect humoral immune function. The level of CD3+ T cells reflects the overall level of cellular immunity. CD4+ T cells can promote B cell differentiation (to induce the production of antibodies), activate other cells so that they secrete lymphatic factor, and play a role in inflammatory reactions and a mediating role. CD8+ T cells are a kind of immune suppression cell, as they inhibit antibody secretion and T-cell proliferation.
The results indicated that STG emulsions can improve cellular and humoral immune function. Several clinical and experimental studies [
The immune function inhibition caused by some fat emulsions is mainly related to LCTs, as the fatty acid carbon chains of MCTs do not contain unsaturated double bonds, so MCTs are chemically stable and easily undergo peroxidation. MCTs can be cleared directly and quickly (they are not readily deposited in the liver, lungs, and reticuloendothelial system), and esterification does not readily occur, which can reduce the system load.
During the metabolism of STG emulsions, the MCTs and LCTs are released in a 1 : 1 ratio, so using an STG emulsion does not lead to the accumulation of LCTs resulting from the MCT that is easily metabolized. MCT metabolism does not produce arachidonic acid, which has an inhibitory effect on the immune system. In addition, ketone bodies, which are produced during MCT metabolism, can promote the proliferation of immune and intestinal mucosal epithelial cells [
Several RCTs showed that, among patients receiving MCT/LCT mixtures, serum IgG, IgM, CD3+, and CD4+ levels dropped significantly by the fifth postoperative day, with no significant recovery by the seventh day. In contrast, in patients receiving an STG emulsion, the change in serum IgG, IgM, CD3+, and CD4+ levels was not very obvious by the fifth postoperative day, and these values recovered (to preoperative levels) by the seventh day [
A major limitation of the study was that it only included a small number of high-quality RCTs, which are all coming from the same country, China. Another potential limitation is that some of the RCTs used epidural analgesia so we were unable to exclude its influence on hepatic blood flow (which can affect liver function). However, the type of analgesia did not differ between study groups in any of the RCTs, so any influence on our results is less likely. However, the different types of liver-protecting therapy used in the RCTs may have affected their outcomes and increased the heterogeneity between the included studies.
Compared to physical MCT/LCT mixtures, STG emulsions can safely improve nutritional status while relieving the burden associated with liver metabolism and inflammatory reactions in patients with liver carcinoma after hepatectomy. The meta-analysis showed that STG emulsions were more beneficial than MCT/LCT mixtures in terms of recovery of liver function and immune function. Therefore, STG emulsions represent a promising alternative to other types of lipid emulsion for liver surgery patients. However, large multicenter RCTs are needed to better evaluate the most preferable PN strategies. In addition, further studies are needed to investigate the clinical relevance of the effects of PN strategies, particularly in patients requiring long-term PN, those with preexisting liver injuries, and those undergoing surgery that affects liver function, for example, hemihepatectomy. In summary, PN involving physical MCT/LCT mixtures is likely to cause subclinical hepatic injury, whereas STG emulsions have no detectable effect on hepatocellular integrity.
The authors have no conflicts of interest.