Vivian Marlowe
Alcohol use disorder (AUD) is a brain disorder characterised by an individual's inability to stop or control their drinking, despite the harm it causes to their health, work, and relationships. AUD can range from mild to severe, with severe AUD previously referred to as alcoholism or alcohol dependence. Laboratory tests play a crucial role in detecting and managing AUD. These tests can identify biological markers, such as elevated levels of certain enzymes and metabolites, that indicate excessive alcohol consumption and help monitor abstinence. The choice of laboratory test depends on the specific context, such as suspicion of alcohol exposure, trauma-related injuries, or abnormalities in certain biomarkers. This introduction sets the stage for exploring the laboratory finding commonly associated with chronic alcohol dependence, providing insights into the diagnostic and monitoring approaches in addressing this complex disorder.
| Characteristics | Values |
|---|---|
| Laboratory tests for acute alcohol ingestion | Ethanol, Ethyl glucuronide (EtG), Ethyl sulfate (EtS) tests |
| Useful markers for monitoring abstinence after long-term use | Carbohydrate-deficient transferrin (CDT), Phosphatidylethanol (PEth) |
| Specific markers for acute alcohol exposure | Ethanol, Ethyl glucuronide (EtG), Ethyl sulfate (EtS) |
| Specific markers for chronic alcohol use | Carbohydrate-deficient transferrin (CDT), Phosphatidylethanol (PEth) |
| Non-specific markers | Gamma-glutamyl transferase (GGT), Mean corpuscular volume (MCV), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) |
| Blood alcohol concentration (BAC) criteria for preliminary diagnosis of alcoholism | Men: 5 or more drinks in one day or 15 or more drinks in a week, Women: 4 or more drinks in a day or 8 or more drinks in a week |
| Useful marker for early intervention | Gamma-glutamyl transferase (GGT) |
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What You'll Learn
Ethanol, ethyl glucuronide, and ethyl sulphate tests
Ethanol, ethyl glucuronide (EtG), and ethyl sulphate (EtS) tests are used to detect recent alcohol consumption. EtG and EtS are direct metabolites of ethanol that are present in urine after the ingestion of products containing ethyl alcohol. These metabolites can also result from the use of products that contain alcohol but were not intentionally consumed, such as mouthwash or hand sanitiser.
EtG and EtS are detectable for longer in urine than breath ethanol or urine ethanol after alcohol intake. They are considered good markers of acute, short-term alcohol ingestion (up to 36 hours in the blood and up to 5 days in urine). The sensitivity of these tests is highest in heavy drinkers but wanes after 24 hours and with lower doses.
EtG can be measured using immunoassay or liquid chromatography–mass spectrometry (LC-MS/MS). If using an immunoassay screen, a positive result is then confirmed by LC-MS/MS. EtG has been studied as a marker for alcohol consumption since the 1960s. Despite being the result of a minor elimination pathway, it has become useful as a marker for alcohol consumption.
EtS has all the advantages of EtG. Unlike EtG, EtS is stable in urine at room temperature with no extrarenal sulfate conjugation (false positive) or de-sulfation upon storage (false negative). However, false negatives can occur with EtG due to bacterial degradation (E. coli is the most common bacteria in clinical laboratories) and high levels of β-glucuronidase found in urinary tract infections, kidney disease, and bladder cancer.
The ability of breath ethanol, urine ethanol, urine EtG, and urine EtS to detect continued alcohol consumption in clients in community alcohol treatment has been compared. Urine EtG and EtS showed the optimum diagnostic performance.
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Carbohydrate-deficient transferrin and phosphatidylethanol markers
Carbohydrate-deficient transferrin (CDT) is a biomarker for chronic alcohol intake of more than 60 g of ethanol per day. CDT is elevated in the blood of people with heavy alcohol consumption. However, elevated levels can also be found in several medical conditions, including liver disease and hepatitis C. CDT is also known to vary with sex and possibly with age. When used with other tests, such as gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), CDT can be a useful tool in identifying problem drinking or alcohol use disorder.
The use of CDT in patients with liver disease can be problematic. For instance, elevated CDT values may not accurately correlate with alcohol consumption in advanced liver disease. However, CDT can be useful in detecting chronic alcohol consumption and relapses after withdrawal, differentiating patients with enzyme-inducing medication from those with alcohol abuse, and identifying patients with congenital disorders of glycosylation or galactosemia.
Phosphatidylethanol (PEth) is a direct ethanol metabolite and a remarkably good marker of alcohol intake. It can be detected in the blood for up to two weeks of sobriety and is closely correlated with alcohol consumption. PEth testing can be used to monitor alcohol consumption, identify early signs of harmful alcohol consumption, and track cases of alcohol use disorder or dependence. PEth is considered more sensitive than CDT in detecting current regular alcohol consumption.
Both CDT and PEth are specific markers for chronic alcohol use and are useful for monitoring abstinence after long-term alcohol consumption. These markers can help identify problem drinking and support individuals in their journey towards reducing or quitting alcohol consumption.
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Gamma-glutamyl transferase, mean corpuscular volume, and more
Laboratory tests can be used to detect acute alcohol ingestion, monitor abstinence after long-term use, and identify alcohol dependence. While serum ethanol testing provides the most accurate determination of a patient's current alcohol level, other tests are more suitable for detecting chronic alcohol use.
Gamma-glutamyl transferase (GGT) is an indirect marker of alcohol consumption. GGT levels are higher in moderate drinkers than in abstainers, and they increase with age, even in abstinent individuals. However, GGT is not specific to alcohol consumption, as levels may also be elevated due to nonalcoholic fatty liver disease, drug intoxication, obesity, diabetes, and hepatobiliary disorders. Combining GGT testing with carbohydrate-deficient transferrin (CDT) testing increases diagnostic sensitivity and specificity, providing a stronger correlation with actual alcohol consumption. CDT is a collection of various isoforms of the iron transport protein transferrin, and its serum concentrations increase with alcohol consumption above 50-80 g/d for 2-3 weeks. CDT distinguishes chronic heavy drinkers from light social drinkers.
Mean corpuscular volume (MCV), which refers to the average size of a person's red blood cells, is another marker associated with chronic alcohol use. High quantities of alcohol ingestion lead to increased MCV levels. Other nonspecific markers of chronic alcohol use include aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
In addition to laboratory tests, blood pressure measurements can provide insights into alcohol consumption patterns. Both acute and chronic alcohol use are associated with arrhythmias, and even low-level alcohol consumption of one to two drinks per day is linked to increased blood pressure. Heavy alcohol consumption is also associated with an increased risk of hip and other types of fractures, as alcohol disrupts the balance between bone erosion and remodelling, contributing to decreased bone density.
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Acetate levels and the oxidation of alcohol
Chronic alcohol consumption is associated with several pathological consequences and tissue damage. Alcohol metabolism results in the generation of acetaldehyde, a highly reactive and toxic byproduct that may contribute to tissue damage and the formation of damaging molecules known as reactive oxygen species (ROS).
Alcohol is converted to acetate, which serves as a source of energy for the brain. Acetate is produced from the oxidation of acetaldehyde, which is, in turn, produced by alcohol oxidation. The enzymes alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase all contribute to the oxidative metabolism of alcohol. ADH, present in the fluid of the cell (cytosol), converts alcohol (ethanol) to acetaldehyde. CYP2E1, present predominantly in the cell's microsomes, plays a crucial role in metabolizing ethanol to acetaldehyde at elevated ethanol concentrations. Catalase, located in cell bodies called peroxisomes, requires hydrogen peroxide (H2O2) to oxidize alcohol.
Acetaldehyde is rapidly metabolized to acetate, mainly by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria. This process forms acetate and NADH, which is then oxidized by a series of chemical reactions in the mitochondria. In chronic and heavy alcohol consumers, a second pathway becomes prominent: the microsomal ethanol-oxidizing system. This system functions in the smooth endoplasmic reticulum of hepatocytes to convert ethanol to acetaldehyde via cytochrome P450.
Studies have shown that heavy alcohol exposure is associated with higher circulating acetate levels and increased brain uptake of acetate. The increased brain uptake of acetate may explain why cognitive function remains relatively preserved despite reductions in glucose metabolism during acute alcohol consumption. In individuals with alcohol use disorder (AUD), elevated levels of acetate may contribute to compensatory changes in brain metabolism.
Laboratory tests for acute alcohol ingestion include ethanol, ethyl glucuronide (EtG), and ethyl sulfate (EtS) tests. Carbohydrate-deficient transferrin (CDT) and phosphatidylethanol (PEth) are useful markers for monitoring abstinence after long-term alcohol use. PEth testing can help monitor alcohol consumption, identify early signs of harmful consumption, and track cases of alcohol dependence.
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Trait markers and state markers
Laboratory findings can indicate the presence of alcohol use disorder (AUD) or chronic alcohol dependence. AUD is a brain disorder characterised by an individual's inability to stop or control their drinking despite the harm it causes. AUD can be mild, moderate, or severe, and severe AUD is often referred to as alcohol dependence or alcoholism.
Biological markers of alcohol abuse can be divided into two main groups: trait markers and state markers.
Trait markers
Trait markers are genetic, biochemical, or behavioural characteristics that indicate a susceptibility to alcoholism. To be considered useful trait markers, these characteristics must be detectable throughout a person's life, including periods of abstinence and before their first exposure to alcohol.
Genetic factors play a role in the development of AUD, with individuals with a family history of the disorder having an increased risk. Certain mental health conditions, such as depression, post-traumatic stress disorder (PTSD), and attention-deficit/hyperactivity disorder (ADHD), may also increase the risk of developing AUD.
State markers
State markers refer to laboratory abnormalities associated with excessive alcohol consumption. These markers are valuable for the early detection of alcohol abuse and the secondary prevention of alcohol-related problems. While there is currently no single test that satisfies all the criteria of an ideal marker, several potential markers are under evaluation.
Biochemical abnormalities associated with long-term alcohol abuse include elevated levels of acetate, which is a product of alcohol metabolism. Accelerated oxidation of alcohol in the liver leads to increased levels of acetate in the bloodstream. This marker is particularly useful as it differentiates between alcoholics and non-alcoholics, with 65% of intoxicated alcoholics exhibiting elevated acetate levels compared to only 8% of intoxicated non-alcoholics.
Another useful marker is gamma-glutamyl transferase (GGT), an enzyme involved in protein metabolism. Excessive long-term alcohol consumption causes GGT to be released from the liver into the bloodstream. Elevated GGT levels can be detected before the onset of alcohol-related liver injury, making it a valuable marker for early intervention. GGT is currently the most commonly used single laboratory marker for detecting alcohol abuse. However, it is important to note that GGT levels may also be influenced by factors such as nonalcoholic fatty liver disease, drug intoxication, obesity, diabetes, and hepatobiliary disorders.
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Frequently asked questions
AUD is a brain disorder in which a person cannot stop or control their drinking, even though it causes distress and harm. It can cause problems in work, relationships, and health. AUD can be mild, moderate, or severe, and was previously called alcohol dependence or alcoholism.
Treatment options include behavioural treatment, medication, and support groups. Behavioural treatment involves working with addiction counsellors or psychologists to change drinking behaviour. The U.S. Food & Drug Administration has approved naltrexone and acamprosate as AUD medications, and topiramate and gabapentin can also reduce cravings. Support groups can provide peer support and help individuals stop or cut back on drinking.
Laboratory abnormalities associated with chronic alcohol dependence include elevated levels of gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Carbohydrate-deficient transferrin (CDT) and phosphatidylethanol (PEth) are also specific markers for chronic alcohol use.
