Association of triglyceride-glucose index with long-term prognosis in advanced hepatocellular carcinoma patients receiving immunotherapy and targeted therapy

doi:10.3748/wjg.v31.i30.109863

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World Journal of Gastroenterology

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World J Gastroenterol. Aug 14, 2025; 31(30): 109863
Published online Aug 14, 2025. doi: 10.3748/wjg.v31.i30.109863

Table 1 Baseline characteristics of triglyceride-glucose index < 1.58 and triglyceride-glucose index ≥ 1.58, mean ± SD/n (%)

Variables	Overall (N = 278), mean ± SD (%)	Low TyG index (n = 134)	High TyG index (n = 144)	P value
BMI, kg/m²	22.67 ± 2.89	21.86 ± 2.68	23.53 ± 2.87	< 0.001^a
Fasting glucose, mg/dL	5.47 ± 1.24	4.83 ± 0.80	6.56 ± 1.10	< 0.001^a
Fasting triglycerides, mg/dL	1.73 ± 0.42	1.42 ± 0.27	2.07 ± 0.25	< 0.001^a
Tyg index	1.66 ± 0.56	1.24 ± 0.43	2.12 ± 0.23	< 0.001^a
Age, years				0.673
< 60	125 (44.96)	62 (46.27)	63 (43.75)
≥ 60	153 (55.04)	72 (53.73)	81 (56.25)
Sex				0.637
Female	141 (50.72)	66 (49.25)	75 (52.08)
Male	137 (49.28)	68 (50.75)	69 (47.92)
Drinking history				0.428
No	191 (68.71)	89 (66.42)	102 (70.83)
Yes	87 (31.29)	45 (33.58)	42 (29.17)
Smoking history				0.887
No	192 (69.06)	92 (68.66)	100 (69.44)
Yes	86 (30.94)	42 (31.34)	44 (30.56)
ECOG				0.183
0	182 (65.47)	93 (69.40)	89 (61.81)
1	96 (34.53)	41 (30.60)	55 (38.19)
Hypertensive				0.545
No	169 (60.79)	79 (58.96)	90 (62.50)
Yes	109 (39.21)	55 (41.04)	54 (37.50)
Diabetes				0.132
No	210 (75.54)	112 (83.58)	98 (68.06)
Yes	68 (24.46)	22 (16.42)	46 (31.94)
HBV DNA (IU/mL)				0.216
HBV ≤ 2000	147 (52.88)	76 (56.72)	71 (49.31)
HBV > 2000	131 (47.12)	58 (43.28)	73 (50.69)
AFP, ng/mL				0.431
< 1210	126 (45.38)	64 (47.76)	62 (43.06)
≥ 1210	152 (54.68)	70 (52.24)	82 (56.94)
HBe				0.328
Negative	202 (72.66)	101 (75.37)	101 (70.14)
Positive	76 (27.34)	33 (24.63)	43 (29.86)
Metastasis				0.178
No	190 (68.35)	94 (70.15)	96 (66.67)
Yes	88 (31.65)	40 (29.85)	48 (33.33)
Child-Pugh class				0.241
A	158 (56.83)	81 (60.45)	77 (53.47)
B	120 (43.17)	53 (39.55)	67 (46.53)
BCLC stage				0.830
B	145 (52.16)	69 (51.49)	76 (54.17)
C	133 (47.84)	65 (48.51)	68 (45.83)
PVTT				0.215
No	212 (76.26)	104 (77.71)	108 (75.00)
Yes	66 (23.74)	30 (22.29)	36 (25.00)
ALT (U/L)				0.683
≤ 40	150 (53.96)	74 (47.76)	76 (52.78)
> 40	128 (46.04)	60 (52.24)	68 (47.22)
Total bilirubin (μmol/L)				0.182
> 34	173 (62.23)	78 (58.21)	95 (65.97)
≤ 34	105 (37.77)	56 (41.79)	49 (34.03)
Cirrhosis				0.213
No	149 (53.60)	77 (57.46)	72 (50.00)
Yes	129 (46.40)	57 (42.54)	72 (50.00)
Interventional				0.845
No	156 (56.12)	76 (56.72)	80 (55.56)
Yes	122 (43.88)	58 (43.28)	64 (44.44)

^aP < 0.05.

TyG: Triglyceride-glucose; BMI: Body mass index; ECOG: Eastern Cooperative Oncology Group; HBV: Hepatitis B virus; AFP: Alpha-fetoprotein; HBe: Hepatitis B e; BCLC: Barcelona Clinic Liver Cancer; PVTT: Portal vein tumor thrombosis; ALT: Alanine aminotransferase.

Table 2 Tumor responses of triglyceride-glucose index < 1.58 and triglyceride-glucose index ≥ 1.58, n (%)

Variables	Low TyG index (n = 134)	High TyG index (n = 144)	χ²	P value
CR
0	133 (99.25)	144 (100.00)
1	1 (0.75)	0 (0.00)
PR
0	105 (78.36)	126 (87.50)
1	29 (21.64)	18 (12.50)
SD
0	78 (58.21)	88 (61.11)
1	56 (41.79)	56 (38.89)
PD
0	86 (64.18)	74 (51.39)
1	48 (35.82)	70 (48.61)
ORR			4.75	0.029^a
0	104 (77.61)	126 (87.50)
1	30 (22.39)	18 (12.50)
DCR			4.65	0.031^a
0	48 (35.82)	70 (48.61)
1	86 (64.18)	74 (51.39)

^aP < 0.05.

TyG: Triglyceride-glucose; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progression disease; ORR: Objective responds rates; DCR: Disease control rates.

Table 3 Univariate and multivariate analyses of prognostic factors for progression-free survival

Factors	Univariate		Multivariate
Factors	HR (95%CI)	P value	HR (95%CI)	P value
AFP (≤ 1210 vs > 1210), ng/mL	2.22 (1.50-3.29)	< 0.001^a	1.73 (1.15-2.62)	0.009^a
Age (< 60 vs ≥ 60), years	1.03 (0.71-1.50)	0.881	-	-
ALT (≤ 40 vs > 40), U/L	1.08 (0.74-1.56)	0.705	-	-
BCLC stage (B vs C)	2.35 (1.60-3.46)	< 0.001^a	1.97 (1.32-2.94)	< 0.001^a
BMI (< 25 vs ≥ 25), kg/m²	0.51 (0.29-0.89)	< 0.001^a	0.55 (0.37-0.83)	0.037^a
Child-Pugh score (C vs B)	0.94 (0.65-1.37)	0.757	-	-
Diabetes (no vs yes)	1.05 (0.63-1.73)	0.861	-	-
Cirrhosis (yes vs no)	0.82 (0.56-1.20)	0.308	-	-
ECOG (0-1 vs 2)	2.07 (1.40-3.08)	< 0.001^a	1.68 (1.11-2.53)	0.014^a
HBe (positive vs negative)	0.89 (0.59-1.35)	0.587	-	-
HBV-DNA (HBV ≤ 2000 vs HBV > 2000), IU/mL	1.05 (0.72-1.52)	0.802	-	-
Hypertensive (no vs yes)	1.06 (0.72-1.56)	0.777	-	-
PVTT (no vs yes)	1.27 (0.88-1.85)	0.203	-	-
Metastasis (no vs yes)	1.88 (1.28-2.74)	0.001^a	1.66 (1.13-2.45)	0.010^a
Sex (male vs female)	1.08 (0.74-1.56)	0.697	-	-
TyG index (high vs low)	0.45 (0.30-0.67)	< 0.001^a	0.55 (0.37-0.83)	0.005^a
Total bilirubin (> 34 vs ≤ 34), μmol/L	0.98 (0.67-1.45)	0.993	-	-
Interventional (no vs yes)	1.03 (0.71-1.50)	0.875	-	-

^aP < 0.05.

HR: Hazard ratio; CI: Confidence interval; AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; BCLC: Barcelona Clinic Liver Cancer; BMI: Body mass index; ECOG: Eastern Cooperative Oncology Group; HBe: Hepatitis B e; HBV: Hepatitis B virus; PVTT: Portal vein tumor thrombosis; TyG: Triglyceride-glucose index.

Table 4 Univariate and multivariate analyses of prognostic factors for overall survival

Factors	Univariate		Multivariate
Factors	HR (95%CI)	P value	HR (95%CI)	P value
AFP (≤ 1210 vs > 1210), ng/mL	2.15 (1.44-3.21)	< 0.001^a	1.51 (1.01-2.28)	0.046^a
Age (< 60 vs ≥ 60), years	1.14 (0.78-1.67)	0.507	-	-
ALT (≤ 40 vs > 40), U/L	1.11 (0.76-1.62)	0.575	-	-
BCLC stage (B vs C)	2.40 (1.62-3.53)	< 0.001^a	1.87 (1.25-2.80)	0.002^a
BMI (< 25 vs ≥ 25), kg/ m²	0.72 (0.44-1.19)	0.202	-	-
Child-Pugh score (B vs C)	1.02 (0.70-1.49)	0.906	-	-
Diabetes (yes vs no)	0.94 (0.56-1.58)	0.820	-	-
Cirrhosis (no vs yes)	1.29 (0.88-1.88)	0.189	-	-
ECOG (0-1 vs 2)	2.28 (1.52-3.42)	< 0.001^a	1.71 (1.12-2.61)	0.012^a
HBe (negative vs positive)	1.20 (0.81-1.79)	0.364	-	-
HBV-DNA (HBV ≤ 2000 vs HBV > 2000), IU/mL	1.01 (0.69-1.48)	0.954	-	-
Hypertensive (yes vs no)	0.97 (0.65-1.45)	0.887	-	-
PVTT (no vs yes)	1.37 (0.94-2.00)	0.101	-	-
Metastasis (no vs yes)	1.78 (1.21-2.62)	0.003^a	1.58 (1.07-2.33)	0.021^a
Sex (male vs female)	1.05 (0.72-1.53)	0.794	-	-
TyG index (high vs low)	0.37 (0.25-0.56)	< 0.001^a	0.48 (0.31-0.72)	< 0.001^a
Total bilirubin (≤ 34 vs > 34), μmol/L	1.23 (0.84-1.81)	0.286	-	-
Interventional (no vs yes)	1.09 (0.75-1.58)	0.666	-	-

^aP < 0.05.

Table 5 Comparison of features between the training and validation sets, n (%)

Characteristic	Test (n = 84)	Train (n = 194)	χ²	P value
Age, years			0.10	0.747
< 60	39 (46.43)	86 (44.33)
≥ 60	45 (53.57)	108 (55.67)
Sex			0.79	0.375
Female	46 (54.76)	95 (48.97)
Male	38 (45.24)	99 (51.03)
BMI, kg/m²			0.81	0.369
< 25	64 (76.19)	157 (80.39)
≥ 25	20 (23.81)	37 (19.07)
TyG index			0.02	0.894
Low	41 (48.81)	93 (47.94)
High	43 (51.19)	101 (47.94)
HBV-DNA			0.80	0.371
HBV ≤ 2000	41 (48.81)	106 (54.64)
HBV > 2000	43 (51.19)	88 (45.36)
HBe			0.08	0.778
Negative	62 (73.81)	140 (72.16)
Positive	22 (26.19)	54 (27.84)
ECOG			0.07	0.785
0-1	54 (64.29)	128 (65.98)
2	30 (35.71)	85 (34.02)
Child-Pugh score			0.00	0.961
B	44 (52.38)	101 (56.19)
C	40 (47.62)	93 (43.81)
PVTT			1.55	0.213
No	60 (71.43)	152 (78.35)
Yes	24 (28.57)	42 (21.65)
Diabetes			2.41	0.121
No	59 (70.24)	153 (83.15)
Yes	25 (29.76)	41 (16.85)
AFP, ng/mL			0.65	0.420
< 1210	35 (41.67)	91 (46.91)
≥ 1210	49 (58.33)	103 (53.09)
BCLC class			1.58	0.208
B	39 (46.43)	106 (54.64)
C	45 (53.57)	88 (45.36)
Metastasis			1.66	0.197
No	62 (73.81)	128 (65.98)
Yes	22 (26.19)	66 (34.02)
ALT			0.76	0.384
≤ 40	42 (50.00)	108 (55.67)
> 40	42 (50.00)	86 (44.33)
Total bilirubin			0.22	0.642
≤ 34	54 (64.29)	119 (61.34)
> 34	30 (35.71)	75 (38.66)
Cirrhosis			0.07	0.798
No	46 (54.76)	103 (53.09)
Yes	38 (45.24)	91 (46.91)
Interventional			0.57	0.451
No	50 (59.52)	106 (54.64)
Yes	34 (40.48)	88 (45.36)
Hypertensive			0.13	0.720
No	46 (54.76)	123 (63.40)
Yes	38 (45.24)	50 (36.60)

BMI: Body mass index; TyG: Triglyceride-glucose; HBV: Hepatitis B virus; HBe: Hepatitis B e; ECOG: Eastern Cooperative Oncology Group; PVTT: Portal vein tumor thrombosis; AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; ALT: Alanine aminotransferase.

Table 6 Treatment-related adverse events in patients with hepatocellular camrelizumab, n (%)

Variables	Low TyG index (n = 134)	High TyG index (n = 144)	χ²	P value
All grades: Rash	51 (38.06)	62 (43.06)	0.72	0.397
All grades: Nausea	44 (32.84)	53 (36.81)	0.48	0.488
All grades: Fatigue	44 (32.84)	50 (34.72)	0.11	0.740
All grades: Diarrhea	42 (31.34)	47 (32.64)	0.05	0.817
All grades: Hypertension	15 (11.19)	32 (22.22)	6.01	0.014^a
All grades: RCCEP	14 (10.45)	16 (11.11)	0.03	0.859
All grades: Hypothyroidism	18 (13.43)	15 (10.42)	0.60	0.437
All grades: Elevated ALT	12 (8.96)	15 (10.42)	0.17	0.681
All grades: Elevated AST	12 (8.96)	17 (11.81)	0.60	0.437
All grades: Thrombocytopenia	10 (7.46)	12 (8.33)	0.07	0.788
All grades: Leukopenia	20 (14.93)	19 (13.19)	0.17	0.678
All grades: Neutropenia	17 (12.69)	15 (10.42)	0.35	0.554
All grades: Proteinuria	8 (5.97)	10 (6.94)	0.11	0.742
All grades: Pneumonitis	8 (5.97)	5 (3.47)	0.97	0.324
All grades: Myocarditis	5 (3.73)	7 (4.86)	0.21	0.643
≥ 3 grades: Rash	22 (16.41)	26 (18.06)	0.13	0.718
≥ 3 grades: Nausea	14 (10.45)	21 (14.58)	1.08	0.299
≥ 3 grades: Fatigue	15 (11.19)	18 (12.50)	0.11	0.737
≥ 3 grades: Diarrhea	10 (7.46)	13 (9.03)	0.22	0.636
≥ 3 grades: Hypertension	5 (3.73)	13 (9.03)	3.22	0.073
≥ 3 grades: RCCEP	2 (1.49)	3 (2.08)	0.01	0.935
≥ 3 grades: Hypothyroidism	5 (3.73)	4 (2.78)	0.01	0.912
≥ 3 grades: Elevated ALT	4 (2.99)	6 (4.17)	0.04	0.837
≥ 3 grades: Elevated AST	3 (2.24)	6 (4.17)	0.32	0.570
≥ 3 grades: Proteinuria	2 (1.49)	2 (1.39)	0.19	0.666
≥ 3 grades: Leukopenia	6 (4.48)	8 (5.56)	0.17	0.681
≥ 3 grades: Neutropenia	5 (3.73)	4 (2.78)	0.01	0.912
≥ 3 grades: Myocarditis	0 (0.00)	2 (1.39)	0.43	0.499
≥ 3 grades: Pneumonitis	0 (0.00)	0 (0.00)	-	-
≥ 3 grades: Thrombocytopenia	0 (0.00)	0 (0.00)	-	-

^aP < 0.05.

TyG: Triglyceride-glucose; RCCEP: Reactive cutaneous capillary endothelial proliferation; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Citation: Li GC, Yao ZY, Mao HS, Han ZX. Association of triglyceride-glucose index with long-term prognosis in advanced hepatocellular carcinoma patients receiving immunotherapy and targeted therapy. World J Gastroenterol 2025; 31(30): 109863
URL: https://www.wjgnet.com/1007-9327/full/v31/i30/109863.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i30.109863