The Role of the Clinical Laboratory in Nutritional Assessment
Aruna Bakhru in Nutrition and Integrative Medicine, 2018
The two primary biomarkers of alcoholism are gamma glutamyl transferase (GGT) and carbohydrate-deficient transferrin (CDT).32 Phosphatidylethanol is another biomarker of regular alcohol consumption. In a 1989 study, 19 of 22 (86%) self-reported alcoholics had elevated CDT levels, versus none of 47 patients with non-alcoholic liver disease.33 In a more current study, of the various biomarkers for alcoholism, CDT had the highest area under the curve (0.77), followed by GGT (0.68).34 The percentage of excessive drinkers with aspartate aminotransferase:alanine aminotransferase ratio (AST:ALT) >2 was only 2%, a very low sensitivity. CDT typically normalizes within weeks of abstinence. Importantly, there are other causes of elevated CDT levels, including congenital disorders of glycosylation (e.g., hereditary fructosamine and galactosemia) and other genetic and nongenetic causes of liver disease.
Endotoxin Effects on Synthesis of Phosphatidic Acid and Phosphatidic Acid–Derived Diacylglyceride Species
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
The second PA species observed in this peak was synthesized later in GMC whole cell membranes or microsomal membranes after stimulation with lipid A (>60–90 sec). It was derived from the activity of a phospholipase D (PLD) apparently directed against phosphatidylethanolamine (PE) and was characterized by masses (FAB NI [M-H]-/z) in the 705–737 range, enriched in 1-alkyl/alkenyl (sn-1 ether and vinyl ether) species, and had significant C20 and C22 unsaturated species content (21). The provenance of this PA species was verified by the formation of phosphatidylethanol when GMC were stimulated with lipid A in the presence of ethanol (the transphosphatidylation reaction characteristic of PLD in the presence of C2–C4 primary alcohols (see Refs. 20–23). These PA species were subsequently also converted to diradylglycerols, indicating that PAP activation was persistent for at least the observed time course. In summary, lipid A stimulation of GMC resulted in the activation of several mechanisms for the synthesis of PA species, including the enzymes LPAAT and PE-directed PLD, to which the primary response, occurring very rapidly, was activation of LPAAT. Preliminary evidence indicates that the unsaturated PA produced by LPAAT may act as an amplification factor by stimulating PE-PLD but that this may also occur through direct stimulation of PE-PLD by lipid A. PA species were subsequently converted into DG and/or diradylglycerols by the action of PAP. It remains unclear in biological systems whether these diradylglycerol species have specific biological effects or if this represents simply catabolism (or deactivation) of PA. These effects of lipid A are summarized in Figure 1.
Toxicological and Biochemical Analyses
Julian L Burton, Guy Rutty in The Hospital Autopsy, 2010
When assays for ethanol are carried out on blood removed from a putrefied body then questions inevitably arise as to the validity of the results obtained. The question obviously arises as to whether or not the ethanol present in the sample has arisen as a result of ante-mortem alcohol ingestion or postmortem fermentation. Where the sample does not have an adequate amount of fluoride preservative added, then alcohol production can take place in the collection tube. If the alcohol analysis has been carried out by head-space gas–liquid chromatography and there are a number of peaks present on the tracing other than ethanol and the internal standard, the implication is that other volatiles are present. It is likely, when the sample has come from a putrefied body, that they are present as a result of post-mortem fermentation. Culture of the sample may reveal the presence of alcohol-producing organisms. A simpler technique may be simply to leave the sample at room temperature and to repeat the analysis a week later. If alcohol-producing organisms are present in the sample then the alcohol concentration will normally have increased in the interim. If blood samples are taken from multiple sites in the body and there is a discrepancy in their blood alcohol concentrations, then the implication that post-mortem fermentation is confusing the issue is an obvious one. The possibility that alcohol present in the stomach at the time of death might have diffused to the sampling sites should also be considered. Thus, if blood alcohol analyses are to be carried out on samples collected from a putrefied body, blood samples should be obtained from several sites, those sites being carefully specified on the sample tubes, the analyses should be carried out by head-space gas–liquid chromatography, and aliquots of the samples should be submitted for microbiological examination. Samples of vitreous humour can also assist in this situation. Markers of recent alcohol ingestion other than ethanol, such as ethyl glucuronide, ethyl sulphate and phosphatidylethanol, are becoming increasingly available and can be invaluable in helping to address the possibility of alcohol use when a body is showing signs of putrefaction.
Administrative coding for non-alcoholic fatty liver disease is accurate in Swedish patients
Published in Scandinavian Journal of Gastroenterology, 2023
Hanne Åström, Axel Wester, Hannes Hagström
We evaluated the presence of coexisting liver diseases to identify patients with ‘pure’ NAFLD. These included 1) alcohol-related liver disease, defined as either a history of overconsumption of alcohol (≥30 g/day in men and ≥20 g/day in women), phosphatidylethanol levels ≥0.3 μmol/L, if a physician documented a high alcohol consumption without note of the quantity, or a diagnostic code for alcohol use disorders (ICD-10: F10.0–F10.7W) or alcohol-related liver disease (ICD-10: K70.0–K70.9); 2) signs of hepatitis B or hepatitis C defined as either presence of hepatitis B surface antigen, hepatitis C RNA or hepatitis C antibodies on testing, or a diagnostic code for viral hepatitis (ICD-10: B18); 3) signs of autoimmune liver disorders (autoimmune hepatitis [K75.4], primary biliary cholangitis [K74.3], or primary sclerosing cholangitis [K83.0A]), requiring that an ICD-10 diagnosis was made by a specialist in hepatology using standard criteria; or 4) an ICD-10 code for any other competing chronic liver disease (hemochromatosis [E83.1] Wilson’s disease [E83.0B], alpha-1-antitrypsin deficiency [E88.0A], porphyria [E80], or other rare liver-related diagnoses). We required that none of these criteria were met before, at, or within six months after the NAFLD diagnosis, to define ‘pure ‘NAFLD.
Blood phosphatidyl ethanol levels as a tool to detect alcohol misuse in trauma patients
Published in Clinical Toxicology, 2021
Fernando Engel Gerbase, Mariane Tegner, Maria Eduarda Krutzmann, Victória Vendramini Muller, Jonatan de Andrade Alff, Vanessa Becher da Silva, Octaviano Pereira Sagrilo, Rafael Linden, Marina Venzon Antunes
In recent years, phosphatidylethanol (PEth), a direct ethanol biomarker, has attracted special attention as a novel method of alcohol misuse screening in blood [26]. PEth is formed only in the presence of ethanol. Therefore, the diagnostic specificity of PEth as an alcohol marker is theoretically 100% [27]. The half-life of PEth in human blood is about 4–6 days, and it can be detected after 28 days of sobriety [28]. The blood concentration of PEth is correlated with the amount of alcohol ingested in the previous 2–4 weeks, making possible the classification of different drinking patterns [29]. PEth has repeatedly outperformed traditional indirect alcohol biomarkers such as carbohydrate-deficient transferrin (%CDT), gamma glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV) to detect alcohol use disorders in different scenarios [30,31]. Also, blood measurements of PEth evidenced underreporting of alcohol use when self-reported questionnaires were used, in different populations [24,26,32,33].
Relationship between cardiovascular risk factors and binge drinking among college students in South Korea
Published in Journal of Ethnicity in Substance Abuse, 2020
Minkyung Kang, Shane A. Phillips, Mariann R. Piano
Prior to the study visit, participants fasted overnight; all visits were scheduled between 8 am and 12 pm. After questionnaire completion, venous blood was collected into either serum separator tubes or tubes containing sodium citrate for measurement of hs-CRP, fibrinogen, and a lipid profile (TC, HDL-c, low-density lipoprotein cholesterol [LDL-c], and triglycerides [TG]). Tubes were centrifuged, and plasma was removed and stored at 4 °C. All samples were shipped within 24 hours of collection to a commercial laboratory (Seoul Clinical Laboratory; Korea). In a subset of participants, the direct alcohol biomarker phosphatidylethanol (PEth) was measured to confirm drinking status. For PEth measurement, blood spots were placed onto blood spot cards, which were shipped to the U.S. Drug Testing Laboratory (USDTL; Des Plaines, IL). The detection limit for dried blood spot PEth analysis was 8 ng/mL; PEth levels >8 ng/mL were considered evidence of moderate to heavy drinking (Piano et al., 2015).
Related Knowledge Centers
- Alcohol Intoxication
- Carbohydrate Deficient Transferrin
- Fatty Acid
- Phosphate
- Phospholipase D
- Phospholipid
- Lipid-Gated Ion Channels
- Biomarker
- Ethyl Sulfate
- Side Chain