Laboratory Markers of Alcohol Abuse

Pekka Sillanaukee

Alcohol Related Diseases, Pharmacia & Upjohn Diagnostics AB, Sweden, and University of

Tampere, Medical School, Finland

Alcohol consumption in many parts of Europe has increased considerably in the past 25

years, and with it alcohol-related problems have risen sharply. Consequently, more patients

seen in clinical practice as well as among drunk drivers have an underlying alcohol problem.

The need for accurate methods for detection and monitoring of alcohol abuse in different

health care settings is huge.

Despite the need there is no exact clinical finding or symptom in a patient history, in an

interview or in a clinical status that is sufficiently sensitive and specific to detect alcohol

abuse in its early phase. The clinical signs o f alcohol abuse are rather minimal in the early

phase o f alcohol abuse while most o f the signs arise later, after several years o f excessive

drinking. Alcohol consumption is usually under-reported in interviews. Alcohol abusers tend

to underestimate their drinking even more than the social drinkers (Poikolainen, 1995). For

example, in our study among heavy drinkers who were willing to participate in a brief

intervention treatment the typical first self-reported alcohol consumption was only 124

g/week among males and 73 g/week among females (Sillanaukee, 1995). The reliability of

personal interviews about alcohol consumption is difficult. This is especially true when the

individual is trying to get feedback about his/her excessive drinking.

The reasons for using biological laboratory markers are that they give objective information

about alcohol consum ption and changes in drinking habits. Consequently, laboratory tests are

useful in screening heavy drinking; in decision making about the role of alcohol as an

etiologic factor o f disease; in follow-up and monitoring changes in alcohol consumption; in

m otivating patients to change their drinking habits by showing alcohol-induced changes in

their bodies; and, finally, in picking up patients who are sensitive for alcohol-induced

problems.

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Thus, the search for more objective laboratory markers of alcohol abuse has been active.

Several laboratory abnormalities based on hematological characteristics, liver enzyme

activities, lipids, immune function factors, hormones, neurological factors have been

observed to be associated with alcohol abuse (Holt et al, 1981; Cushman et al, 1984; Watson

et al, 1986; Salaspuro, 1986 and 1989; Nilssen and Huseby, 1992; Mihas and Tavassoli,

1992; Stibler, 1992; Allen et al, 1994).

Blood, urine or breath ethanol analyses (5HTOL) and creatinine or 5-hydroxyindoleactic acid

(HIAA) in urine have been proposed to be a specific short-term marker for alcohol

consumption (Voltaire et al, 1992; Helander et al, 1995). 5HTOL stays elevated 6-20 hours

after ethanol disappearance. False positive values have been reported in patients using drugs

inhibiting aldehyde dehydrogenase. If the 5HTOL ratio to creatinine (instead of HIAA) is

used also serotonine rich food may cause false positive values. The marker seems to be

promising, having high sensitivity and specificity for detecting recent alcohol consumption.

The measurement is based on GC-MS technique or HPLC with electrochemical detection

(Helander, 1992) and thus the problem is the difficulty o f routine application today.

Elevated serum levels of membrane-bound enzyme, eamma-elutamvl transferase (GGT) have

been widely used as a marker of alcohol abuse. The sensitivity of GGT in detecting alcohol

abuse has been reported to vary between 34% and 85%. GGT is not increased after acute

alcohol intake but needs probably alcohol consumption of 80-200 g/day for one or several

weeks. The half-life o f elevated GGT is between two and three weeks. In addition to alcohol

abuse increased GGT is frequently found in non-alcoholic liver disease, diabetes, obesity,

pancreatitis, hyperlipidemia, heart failure, severe trauma, and in subjects using barbiturates,

antiepileptics or anticoagulants. Despite its poor specificity, 50-72% of elevated GGT values

can be explained by an excessive alcohol consumption (Kristenson et al, 1980; Penn et al,

1981; Suokas, 1992).

Mean corpuscular volume (MCV) is an index of red blood cell size. Increased MCV values

have been observed in 34-89% of alcohol abusers (Wu et al, 1974; Unger and Johnson, 1974;

Chick et al, 1981). Increased MCV values are also found in vitamin B12 and folic acid

deficiency, liver diseases, several hematological diseases, hypothyroidism, reticulocytosis, in

users o f antiepileptics, as well as among smokers. Alcohol abuse has been found to explain

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increased MCV values in 89% of men and 56% of women in general practice (Seppa et al,

1991). MCV responds slowly to abstinence and up to 40% may have an elevated MCV value

even after three months o f abstinence (Morgan et al, 1981).

Other widely used markers are serum aspartate aminotransferase (ASAT) and alanine

aminotransferase (ALAT). The intracellular enzymes are more indicative for liver damage

than for alcohol abuse. The pooled sensitivity o f ASAT has been estimated to be 35% as a

marker of alcohol abuse (Rosman and Lieber, 1991). The sensitivity for ALAT may be even

poorer. Increased values are also found in non-alcoholic liver diseases (ASAT, ALAT), in

muscle disorders (ASAT), and in myocardial infraction (ASAT).

One of the recently developed routine laboratory tests for alcohol abuse is serum

carbohydrate-deficient transferrin (CDT). The marker consists o f a-, mono-, and

disialoisoforms of transferrin that are deficient in their terminal trisaccharide. In a recent

review by Helena Sdbler (1992) summarizing 2500 individuals in different studies, a total

clinical sensitivity was 82% and specificity 97%. False positives have been reported in

patients with severe liver diseases (mainly in primary biliary chirrosis, chronic hepatitis C,

hepatic malignities), in patients with genetic D-variant of transferrin, and in patients with an

inborn error of glycoprotein metabolism. In a more recent study Anton and Moak (1994)

reported a sensitivity o f 79% and a specificity of >90% among males who drank more than

60 g/day before admission. During abstinence the CDT values normalize with a mean half-

life o f 14-17 days. Females have higher normal values of CDT than males, possibly due to

asialo- and monosialotransferrin.

CDT has now been shown to have high specificity and a sensitivity that is at least equal to

that of the conventional laboratory markers. CDT values seem to increase after 10 days of

drinking at 50-80 grams of ethanol per day. It has also a relatively good correlation with self-

reported alcohol consumption but not with conventional markers. This combination makes it

suitable for routine work in the detection of alcohol abuse and monitoring either abstinence or

relapse during treatment. Additionally, by following relative changes in CDT and GGT from

each individual’s baseline values, rather than using the conventional population-based cut­

offs, one may improve the detection of relapses in a monitoring situation (Borg et al, 1995;

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Helander et al, 1996). In one study CDT detected relapses even before self-report among

male subjects (Rosman et al, 1995).

The summary table below gives an estimation of the sensitivity, specificity and half-life o f

different laboratory markers of alcohol abuse. Due to the limited sensitivity o f a single

laboratory marker the parallel measurement of CDT with traditional alcohol markers may

increase the possibility to detect alcohol abuse. Recent studies indicate that the combined

measurement of CDT and GGT or CDT and MCV will increase the possibility to detect

alcohol abuse (Allen et al, 1994; Anton and Moak, 1994; Yersin et al, 1995; Helander et al,

1996).

Marker Sensitivity Specificity Half-life/elim ination

ETOH 0 - 1 0 0 1 0 0 1 g/kg/h

5HTOL/HIAA 0-90 >90 5-20 h after ETOH

GGT 34-85 11-85 2-3 weeks

MCV 34-89 26-91 -3 months

AS AT 15-69 low 2-3 weeks

ALAT 26-58 low 2-3 weeks

CDT 39-94 82-100 2 weeks

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