Aims: A combined index based on γ-glutamyltransferase (GGT) and carbohydrate-deficient transferrin (CDT) measurements (GGT–CDT) has been recently suggested to improve the detection of excessive ethanol consumption. The aim of this work was to compare GGT–CDT with the conventional markers of alcohol abuse in individuals with a wide variety of alcohol consumption. Methods: A cross-sectional and follow-up analysis was conducted in a sample of 165 heavy drinkers, consuming 40–540 g of ethanol per day, and 86 reference individuals who were either moderate drinkers (n = 51) or abstainers (n = 35). Results: GGT–CDT (5.35 ± 1.08) in the heavy drinkers was significantly higher than in the reference individuals (3.30 ± 0.37). The sensitivity of GGT–CDT (90%) in correctly classifying heavy drinkers exceeded that of CDT (63%), GGT (58%), mean corpuscular volume (MCV) (45%), aspartate aminotransferase (AST) (47%), and alanine aminotransferase (ALT) (50%), being also essentially similar for alcoholics with (93%) or without (88%) liver disease. When comparing the data using either moderate drinkers or abstainers as reference population, the sensitivity of GGT–CDT, CDT, and ALT remained unchanged whereas the sensitivity of GGT, MCV, and AST was found to show variation. Conclusions: GGT–CDT improves the sensitivity of detecting excessive ethanol consumption as compared with the traditional markers of ethanol consumption. These findings should be considered in the assessment of patients with alcohol use disorders.

Background: Although both ethanol consumption and overweight alter the activities of hepatic enzymes in circulation, the differentiation of an alcohol or nonalcohol basis for such changes remains problematic. The magnitude of alterations occurring among moderate drinkers has remained obscure. Objective: We examined the links between moderate ethanol consumption, body mass index (BMI; in kg/m²), and liver enzymes. Design: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) were recorded from 2164 apparently healthy participants (1028 men, 1136 women) reporting either no alcohol (abstainers) or <40 g ethanol consumption per day (moderate drinkers). The study population was further classified according to BMI as follows: <19 (underweight), ≥19 and <25 (normal weight), ≥25 and <30 (overweight), and ≥30 (obese). Results: Serum ALT (P < 0.05) and GGT (P < 0.001) but not AST (P = 0.805) activities in moderate drinkers were higher than those in abstainers. For all enzymes, a significant main effect was observed of increasing BMI, which was more striking in moderate drinkers than in abstainers. Tests of between-subjects effects indicated significant interactions with sex and drinking status, although not with sex and BMI. Conclusions: The effect of moderate alcohol consumption on liver enzymes increases with increasing BMI. These findings should be considered in the clinical assessment of overweight alcohol consumers and in the definition of normal ranges for liver enzymes. These results may also help to develop new approaches for examining patients with fatty liver induced by either ethanol or adiposity.

Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders.

Carriers of the hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk of NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, and transcriptome using ultra performance liquid chromatography-mass spectrometry and RNA-seq. In carriers and noncarriers of the gene variant, we also measured pathways of hepatic fatty acids (de novo lipogenesis [DNL] and adipose tissue lipolysis [ATL] using ² H ₂ O and ² H-glycerol) and insulin sensitivity using ³ H-glucose and euglycemic-hyperinsulinemic clamp) and plasma cytokines. Carriers and noncarriers had similar age, sex and BMI. Fibrosis was significantly less frequent while phospholipids, but not other lipids, were enriched in the liver in carriers compared with noncarriers. Expression of 274 genes was altered in carriers compared with noncarriers, consisting predominantly of downregulated inflammation-related gene sets. Plasma IL-6 concentrations were lower, but DNL, ATL and hepatic insulin sensitivity were similar between the groups. In conclusion, carriers of the HSD17B13 variant have decreased fibrosis and expression of inflammation-related genes but increased phospholipids in the liver. These changes are not secondary to steatosis, DNL, ATL, or hepatic insulin sensitivity. The increase in phospholipids and decrease in fibrosis are opposite to features of choline-deficient models of liver disease and suggest HSD17B13 as an attractive therapeutic target.