by Jean Deenmamode
The concept of testing breath, blood or urine for alcohol is familiar to the general public, and blood alcohol testing is widely used across a range of industries, from aviation to driver licensing. But is a snapshot alcohol measurement really the best approach to ensuring longterm safety in these industries, or identifying individuals at risk from complications of chronic excessive alcohol consumption?
The risks associated with driving or operating machinery directly after consuming alcohol are widely known, and the ‘morning after’ effects of excess alcohol intake are equally well understood. Unfortunately, the mid- to long-term effects of routinely high alcohol consumption are less widely recognized. Historically, most people have associated this with liver disease, but it is just one facet of disease; it also affects the kidneys, the brain – leading to depression and other neurological problems – fertility, and many other aspects of human physiology. Dealing with the biochemical and psychological changes associated with excess alcohol intake requires a holistic approach, looking at everything from specific biomarkers to physiology and socio-economic factors, with no one-size-fits-all solution.
Recognizing a problem
Regardless of where affected individuals interact with the healthcare system (through primary care, industry-associated mandatory testing or frequent alcohol-related admissions to the emergency department), the first challenge is to establish that there is an issue. Simple blood alcohol level testing only provides a measure of shortterm alcohol consumption – limited to hours, not days – making it easy to ‘cheat’ by simply abstaining from drinking immediately before testing. Liver function tests [including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), albumin and total protein, among others] are commonly used to assess the health of the liver, and can provide an indication of alcohol-associated liver disease, but are obviously highly non-specific and only suggest very long-term alcohol abuse. Similarly, mean corpuscular volume (MCV) – an index of red blood cell size – has historically been used as a marker of excessive alcohol intake, and can be detected even after an extended period of abstinence, but offers poor sensitivity and can be affected by a wide range of other factors.
Gamma-glutamyl transferase (GGT) is one of the most commonly used biomarkers of chronic drinking. Excessive alcohol consumption over a period of weeks significantly raises levels of this liver enzyme, and it takes, on average, three weeks of abstinence for GGT levels to return to within reference limits. The ability of this test to detect long-term heavy drinking in the recent past has made GGT a useful tool for monitoring abstinence, but liver disease – a common problem in recovering alcoholics – can also increase GGT levels, leading to false-positive results.
Ethyl glucuronide (EtG) in urine is another potential marker, and has the advantage of non-invasive sample collection, avoiding the need for a blood draw. When combined with concomitant measurement of ethyl sulphate it provides a meaningful measure of recent alcohol consumption. However, EtG is only present in urine at detectable levels for around four to five days after heavy alcohol consumption, making it a good marker of binge drinking, but limiting its use for more chronic misuse.
Phosphatidylethanol (PEth) testing is increasingly being seen as a reliable method to provide a mid-term picture of alcohol consumption. Phosphatidylethanols are abnormal phospholipids formed in the presence of ethanol, which bind to the membrane of red blood cells. Unfortunately, there are no commercially available PEth assays at this time, making it impractical as a universally applicable biomarker.
One of the most promising biomarkers for chronic excess alcohol consumption is carbohydrate-deficient transferrin (CDT). Like GGT, this is another blood-based protein that increases in concentration with high alcohol intake. In normal serum, the majority of transferrin isoforms will have four carbohydrate moieties attached to them, forming tetrasialotransferrin. High alcohol consumption over a period of one to two weeks leads to a greater percentage of carbohydratedeficient disialotransferrin. For example, consumption of half a bottle of wine, two cans of beer, or 125 ml of spirits daily for a period of seven to 10 days will lead to an elevated CDT result. Furthermore, with a half-life of about two weeks, CDT is a useful ‘retrospective’ marker. The advantage of this over other biomarkers is that it is highly specific to chronic excessive alcohol consumption.