Combination of the CAGE and serum gamma-glutamyl transferase: an effective screening tool for alcohol use disorder and alcohol dependence

Figures & data

Table 1 Subject characteristics

	All (n=394)	Non-PD (NC) (n=91)	PD (n=303)	Non-AUD (n=247)	AUD (n=147)	Non-AD (n=324)	AD (n=70)
Age (Years)	42.72±12.33	48.78±14.07	40.89±11.16	42.46±13.55	43.15±10.00	42.16±13.05	45.30±7.84
Gender (M/F)	309/85	55/36	254/49	177/70	132/15	241/83	68/2
First drinking age	19.611±4.96	21.71±7.40	19.01±3.81	20.09±5.48	18.81±3.85	19.88±5.03	18.39±4.47
Family history of AD (±)	50/344	4/87	46/257	18/229	32/115	28/296	22/48
AUDIT	11.63±9.62	1.76±1.82	14.59±9.01	6.54±4.73	20.18±9.69	8.24±6.08	27.30±7.14
AUDIT sub-category
Alcohol consumption	6.42±3.56	1.63±1.58	7.86±2.60	5.00±3.23	8.81±2.73	5.62±3.34	10.14±1.76
Alcohol dependence	1.93±2.90	0.08±0.40	2.49±3.09	0.52±0.93	4.31±3.47	0.89±1.46	6.77±2.99
Alcohol related-harm	3.27±4.24	0.05±0.35	4.24±4.39	1.02±1.70	7.07±4.52	1.74±2.48	10.39±3.35
CAGE	1.56±1.40	0.35±0.66	1.93±1.36	0.73±0.82	2.97±0.98	1.17±1.16	3.39±0.82
GGT(IU/L)	52.79±74.15	23.13±14.89	61.70±82.12	35.79±38.77	81.37±104.67	39.89±42.68	112.48±135.62

Notes: Data are presented as mean±standard deviation or number.

Abbreviations: NC, normal control; PD, problem drinking; AUD, alcohol use disorder; AD, alcohol dependence; AUDIT, alcohol use disorders identification test; CAGE, cutting down, annoyance by criticism, guilty feeling, and eye-openers; GGT, gamma-glutamyl transferase.

Table 2 Multiple logistic regression analyses treating alcohol use status as a dependent variable

Dependent variable	Independent variable	B	SE	OR (95% CI)	p
PD
	Age	−0.064	0.012	0.938 (0.917–0.961)	<0.001
	Gender	0.229	0.362	1.257 (0.619–2.554)	0.527
	CAGE	1.311	0.204	3.709 (2.485–5.535)	<0.001
	GGT	0.027	0.010	1.027 (1.008–1.048)	0.006
AUD
	Age	0.010	0.014	1.010 (0.983–1.038)	0.464
	Gender	0.076	0.507	1.079 (0.399–2.918)	0.881
	CAGE	2.066	0.208	7.895 (5.251–11.870)	<0.001
	GGT	0.005	0.003	1.005 (0.999–1.012)	0.128
AD
	Age	0.044	0.019	1.045 (1.007–1.085)	0.019
	Gender	2.141	1.044	8.509 (1.100–65.856)	0.040
	CAGE	1.763	0.228	5.829 (3.731–9.106)	<0.001
	GGT	0.008	0.003	1.008 (1.003–1.013)	0.003

Abbreviations: B, regression coefficient; SE, standard error; PD, problem drinking; AUD, alcohol use disorder; AD, alcohol dependence; AUDIT, alcohol use disorders identification test; CAGE, cutting down, annoyance by criticism, guilty feeling, and eye-openers; GGT, gamma-glutamyl transferase.

Table 3 AUROC and cutoff scores for the AUDIT, CAGE, GGT and the combination of CAGE and GGT

	NC vs PD	Non-AUD vs AUD	Non-AD vs AD
AUDIT
AUROC	0.973	0.893	0.970
SE	0.00728	0.0190	0.0106
95% CI	0.951–0.986	0.858–0.922	0.948–0.984
Cutoff	>5	>12	>17
Sen/Spe	90.76/95.60	76.87/89.07	91.43/91.98
CAGE
AUROC	0.834	0.939	0.916
SE	0.0214	0.0124	0.0175
95% CI	0.794–0.869	0.910–0.960	0.884–0.942
Cutoff	>0	>2	>2
Sen/Spe	82.18/74.73	73.47/97.98	88.57/84.26
z score/p-value	6.927/<0.0001*	2.535/0.0112^†	3.233/0.0012*
GGT
AUROC	0.736	0.724	0.799
SE	0.0263	0.0264	0.0257
95% CI	0.690–0.779	0.677–0.767	0.756–0.838
Cutoff	>28	>28	>36
Sen/Spe	61.39/82.42	74.83/62.75	80.00/68.21
z score/p-value	9.482/<0.0001*	6.285/<0.0001*	6.529/<0.0001*
CAGE+GGT
AUROC	0.894	0.944	0.947
SE	0.0175	0.0116	0.0127
95% CI	0.859–0.922	0.917–0.965	0.920–0.967
Logit (case)	>1.063	>0.098	>-1.281
Sen/Spe	79.54/83.52	77.55/96.76	90.00/87.96
z score/p-value	5.301/<0.0001*	2.894/0.0038^†	1.652/0.0985

Notes: The combined CAGE and GGT scores were calculated by equations derived from multiple logistic regression analyses after adjusting for age and gender. Z score/p-value resulted from pairwise comparisons of AUROC (AUDIT vs others). Bonferroni-corrected p<0.0167 (0.05/3) was applied for statistical significance. *Significantly inferior to AUDIT. ^†Significantly superior to AUDIT.

Abbreviations: NC, normal control; PD, problem drinking; AUD, alcohol use disorder; AD, alcohol dependence; AUROC, area under the receiver operating characteristic curves; AUDIT, alcohol use disorders identification test; CAGE, cutting down, annoyance by criticism, guilty feeling, and eye-openers; GGT, gamma-glutamyl transferase; CAGE+GGT, combination of CAGE and GGT; SE, standard error; Sen/Spe, sensitivity/specificity; Pr (case), probability of a case.

Figure 1 ROC curves of the AUDIT, CAGE, GGT and the combination of CAGE and GGT. Notes: The combined CAGE and GGT scores were calculated by equations derived from multiple logistic regression analyses after adjustment for age and gender.

Abbreviations: AUROC, area under the receiver operating characteristic curves; NC, normal control; PD, problem drinking; AUD, alcohol use disorder; AD, alcohol dependence; AUDIT, alcohol use disorders identification test; CAGE, cutting down, annoyance by criticism, guilty feeling, and eye-openers; GGT, gamma-glutamyl transferase; CAGE+GGT, combination of CAGE and GGT.