Insights into the GALAD score: A new optimal cut-off for hepatocellular carcinoma

Table 1 Baseline characteristics of the subjects included in the study, mean ± SD/n (%)

Parameters	Total cohort (n = 1431)	Healthy (n = 704)	Advanced CLD		P value1
			Cirrhosis (n = 551)	HCC (n = 176)
Age (years)	56.52 ± 13.97	50.84 ± 13.69	60.27 ± 11.97	67.49 ± 9.79	0.0001
Gender (male)	908 (63.45)	413 (58.66)	356 (64.61)	139 (78.98)	< 0.0012
BMI (kg/m2)	27.57 ± 5.05	28.03 ± 4.92	27.09 ± 5.15	26.87 ± 5.13	0.0002
Diabetes (yes)	261 (18.24)	37 (5.26)	170 (30.85)	54 (30.68)	< 0.0012
Child-Pugh					0.0022
A			362 (65.70)	94 (53.41)
B			140 (25.41)	69 (39.20)
C			49 (8.89)	13 (7.39)
Etiology					< 0.0012
HBV			52 (9.52)	9 (5.26)
HCV			164 (30.04)	74 (43.27)
MASLD			100 (18.32)	16 (9.36)
Alcohol			126 (23.08)	55 (32.16)
Cryptogenic			3 (0.55)	7 (4.09)
Other			101 (18.50)	10 (5.85)
Blood
Blood sugar (mg/dL)	109.71 ± 32.43	105.71 ± 19.48	123.71 ± 58.79	123.23 ± 41.65	0.03
Bilirubin (mg/dL)	2.22 ± 5.14	0.88 ± 0.31	3.00 ± 6.20	5.64 ± 9.08	0.0001
GPT (U/L)	32.99 ± 52.13	14.80 ± 7.51	54.28 ± 77.23	50.12 ± 42.79	0.0001
GOT (U/L)	33.63 ± 53.05	10.89 ± 2.89	50.78 ± 55.36	77.01 ± 94.40	0.0001
GGT (U/L)	54.68 ± 102.74	12.99 ± 6.73	103.51 ± 132.82	139.30 ± 151.20	0.0001
AFP (ng/mL)	109.31 ± 1236.92	2.06 ± 1.19	24.66 ± 289.01	803.28 ± 3418.54	0.0001
AFP-L3 (%)	4.31 ± 12.53	0.44 ± 3.04	4.09 ± 9.01	20.48 ± 25.82	0.0001
DCP (ng/mL)	20.30 ± 178.29	0.81 ± 13.41	10.05 ± 62.80	130.36 ± 482.28	0.0001

¹Kruskal-Wallis rank test.

²χ² or Fisher’s test when necessary.

HCC: Hepatocellular carcinoma; CLD: Chronic liver disease; BMI: Body mass index; HBV: Hepatitis B virus; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease; GPT: Glutamic pyruvic transaminase; GOT: Glutamic oxaloacetic transaminase; AFP: Alpha-fetoprotein; GGT: Gamma-glutamyl transferase; DCP: Des-gamma-carboxy prothrombin.

Table 2 Comparison of GALAD score distribution between healthy individuals and advanced chronic liver disease groups

GALAD	Groups			P value1	Multiple comparisons2
	Healthy	Cirrhosis	HCC		Cirrhosis vs healthy	HCC vs healthy	HCC vs cirrhosis
mean ± SD	-4.61 ± 1.65	-2.06 ± 2.31	2.36 ± 3.88	0.0001	< 0.0001	< 0.0001	< 0.0001
Median (IQR)	-4.48 (2.37)	-2.21 (2.36)	1.77 (4.45)

¹Kruskal-Wallis rank test.

²Dunn’s test of multiple comparisons adjusted for Bonferroni correction.

IQR: Interquartile range; HCC: Hepatocellular carcinoma.

Table 3 Performance of the GALAD score using healthy individuals or patients with cirrhosis as reference

Response variable	AUC	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
Control (Ref.)
HCC	0.9725; (K-fold = 0.9743); Δ = 0.0018	85.23	98.86	94.94	96.40	96.14
Cirrhosis (Ref.)
HCC	0.8609; (K-fold = 0.8657); Δ = 0.0048	47.73	95.28	76.36	85.09	83.77

Δ was calculated as difference between area under the curve after K-fold and area under the curve calculated with classical approach. AUC: Area under the curve; PPV: Positive predictive value; NPV: Negative predictive value; HCC: Hepatocellular carcinoma.

Table 4 Individual stratification according to risk class categories of hepatocellular carcinoma and GALAD, n (%)

GALAD categories	Very low risk (0%-10%)	Low risk (10%-25%)	Moderate risk (25%-50%)	High risk (50%-75%)	Very high risk (75%-100%)
HCC vs healthy
≤ -1.6699655	953 (100.00)	88 (51.16)	0 (0.00)	0 (0.00)	0 (0.00)
> -1.6699655	0 (0.00)	84 (48.84)	99 (100.00)	59 (100.00)	148 (100.00)
Cirrhosis vs HCC
≤ -0.77471435	953 (100.00)	172 (100.00)	41 (100.00)	0 (0.00)	0 (0.00)
> -0.77471435	0 (0.00)	0 (0.00)	0 (0.00)	15 (100.00)	148 (100.00)

HCC: Hepatocellular carcinoma.