Alcohol A Alcoholism Vol. 31. No. 6, pp. 613-616, 1996
LABORATORY MARKERS OF ALCOHOL ABUSE
PEKKA SILLANAUKEE
Pharmacia & Upjohn Diagnostics, Alcohol Related Diseases, S-75182, Uppsala, Sweden and University of Tampere Medical
School. Tampere, Finland
Abstract — A number of routine laboratory markers provide objective information about alcohol use
and abuse. The usefulness of these markers is discussed One such marker recently developed is serum
carbohydrate-deficient transfemn (CDT). which has a greater overall marker potential than other
existing tests. The use of CDT in combination with some of the other markers is likely to enhance the
detection of alcohol abuse or heavy consumption
markers are that they give objective information
about alcohol consumption and changes in drinking habits. Consequently, laboratory tests are
useful in screening heavy drinking; in decisionmaking about the role of alcohol as an aetiological
factor of disease; in follow-up and monitoring
changes in alcohol consumption; in motivating
patients to change their drinking habits by showing alcohol-induced changes in their body; and
finally in detecting patients who are sensitive for
alcohol-induced problems. The search for more
objective laboratory markers of alcohol abuse has
therefore been active. Several laboratory abnormalities based on haematological characteristics,
liver enzyme activities, lipids, immune factors,
hormones and neurological factors have been
observed to be associated with alcohol abuse
(Holt et al., 1981; Cushman et al., 1984; Watson
etal., 1986; Salaspuro, 1986, 1989; Stibler, 1991;
Nilssen et al., 1992; Mihas and Tavassoli, 1992;
Allen et al., 1994). The following is a brief
description of the most frequently used short- and
long-term markers for alcohol consumption.
INTRODUCTION
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
clearly considerable.
Despite such a need, there is no exact clinical
finding or symptom in a patient history, in an
interview or in a clinical setting that is sufficiently
sensitive and specific to detect alcohol abuse in its
early phase. The clinical signs of alcohol abuse are
rather minimal in the early phase of this process
while most of the signs arise later after several
years of excessive drinking. Also alcohol consumption is usually under-reported in interviews;
alcohol abusers tend to underestimate their drinking even more than the social drinkers (Poikolainen, 1985). For example in our study among heavy
drinkers, who were willing to participate in brief
intervention treatment, the typical first selfreported 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.
USE OF LABORATORY MARKERS
The reasons for using biological laboratory
ETHANOL
Blood, urine or breath ethanol analyses provide
no information about the severity of alcohol drinking, but the presence of an increased tolerance can
be identified. Blood or breath alcohol levels > 1.5%
(35 mmol/1) without gross evidence of intoxication
or >3% (69 mmol/1) at any time has been reported
to be the first-level criterion of alcoholism (National
Council of Alcoholism, 1972). Due to the short halflife of ethanol and the fact that alcohol drinking
does not necessarily mean alcohol abuse, its value
613
© 1996 Medical Council on Alcoholism
P. SILLANAUKEE
614
Table I. Comparisons of markers of alcohol use and abuse
Marker
ETOH
5-HTOL/5-HIAA
GGT
MCV
ASAT
ALAT
CDT
Sensitivity (%)
0-100
0-90
34-85
34-89
15-69
26-58
39-94
Specificity (%)
Half-life/elimination
100
lg/kg/h
5-20 h after ETOH disappearance
2-3 weeks
~ 3 months
2-3 weeks
2-3 weeks
2 weeks
>90
11-85
26-91
low
low
82-100
ETOH = ethanol; 5-HTOL/5-HIAA = 5-hydroxytryptophol/5-hydroxyindol-3-ylacetic acid ratio, GGT = y-glutamyl
transferase; MCV = mean corpuscular volume, ASAT = aspartate aminotransferase; ALAT = alanine aminotransferase; CDT = carbohydrate-deficient transferrin.
as a marker of alcohol abuse is limited.
5-HYDROXYTRYPTOPHOL
The ratio of the serotonin metabolite 5-hydroxytryptophol (5-HTOL) to creatinine or to 5-hydroxyindol-3-ylacetic acid (5-HIAA) in urine has
been proposed to be a specific short-term marker
for alcohol consumption (Voltaire et al., 1992;
Helander et al., 1992a,b). 5-HTOL stays elevated
6-20 h after ethanol disappearance. False-positive
values have been reported in patients using drugs
inhibiting aldehyde dehydrogenase. If the 5-HTOL
ratio to creatinine (instead of 5-HIAA) is used,
serotonin-rich foods may also 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 high-performance liquid
chromatography with electrochemical detection
(Helander et al., 1992a) and thus the problem is
the difficulty of routine application today.
GAMMA-GLUTAMYL TRANSFERASE
An elevated serum level of membrane-bound
enzyme, gamma-glutamyl transferase (GGT) has
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 halflife of elevated GGT is between 2 and 3 weeks. In
addition to alcohol abuse, increased GGT is
frequently found in non-alcoholic liver disease,
diabetes, obesity, pancreatitis, hyperlipidaemia,
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
Mean corpuscular volume (MCV) is an index of
red blood cell size. Increased MCV values have
been observed in 34-89% of alcohol abusers
(Unger and Johnson, 1974; Wu etal., 1974; Chick,
1981). Increased MCV values are also found in
cases of vitamin B|2 and folic acid deficiency,
liver diseases, several haematological disorders,
hypothyroidism, reticulocytosis, in users of antiepileptics, as well as among smokers. Alcohol
abuse has been found to explain 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 3
months of abstinence (Morgan et al., 1981).
SERUM AMINOTRANSFERASES
Other widely used markers are serum aspartate
aminotransferase (ASAT) and alanine aminotransferase (ALAT). These enzymes are more indicative of liver damage than of alcohol abuse. The
pooled sensitivity of ASAT has been estimated to
be 35% as a marker of alcohol abuse (Rosman and
Lieber, 1992). The sensitivity for ALAT may be
even poorer. Increased values are also found in
non-alcoholic liver diseases (ASAT, ALAT), in
LABORATORY MARKERS OF ALCOHOL ABUSE
muscle disorders (ASAT) and in myocardial
infarction (ASAT).
CARBOHYDRATE-DEFICIENT
TRANSFERRED
One of the recently developed routine laboratory tests for alcohol abuse is serum carbohydratedeficient transferrin (CDT). The marker consists
of the asialo, monosialo and disialo isoforms of
transferrin that are deficient in their terminal
trisaccharides. In a recent review by Stibler
(1991), summarizing 2500 individuals in different
studies, a total clinical sensitivity of 82% and
specificity of 97% were estimated. False-positives
have been reported in patients with severe liver
diseases (mainly in primary biliary cirrhosis,
chronic hepatitis C, hepatic malignancies), 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 of 79% and
specificity of >90% among males who drank
>60g/day before admission. During abstinence,
the CDT values normalize with a mean half-life of
14-17 days. Females have higher normal values of
CDT than males, possibly due to asialo- and
monosialo-transferrin.
CDT has now been shown to have a 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 a level of 50-80 g ethanol per day. It also has 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
for monitoring either abstinence or relapse during
treatment. Additionally, following
relative
changes in CDT and GGT from each individual's
baseline values, rather than using the conventional
population-based cut-offs, may improve the detection of relapses in a monitoring situation (Borg et
al., 1995; Helander et al., 1996). In one study,
CDT indicated relapses even before self-report
among male subjects (Rosman et al., 1995).
CONCLUSION AND COMMENTS
Table 1 summarizes the sensitivities, specificities and half-lives of different laboratory mar-
615
kers of alcohol abuse. Due to the limited
sensitivity of any single laboratory marker, the
parallel measurement of CDT with traditional
alcohol markers may enhance the ability to detect
alcohol abuse. Recent studies indicate that the
combined measurement of CDT and GGT or of
CDT and MCV could achieve such an enhancement (Allen et al., 1994; Anton and Moak, 1994;
Yersin et al., 1995; Helander et al., 1996).
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