Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy

doi:10.3748/wjg.v30.i37.4132

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Oct 7, 2024 (publication date) through Jan 1, 2025

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World Journal of Gastroenterology

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1007-9327

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Retrospective Study

World J Gastroenterol. Oct 7, 2024; 30(37): 4132-4148
Published online Oct 7, 2024. doi: 10.3748/wjg.v30.i37.4132

Table 1 Baseline characteristics of the body mass index < 25 kg/m² and body mass index ≥ 25 kg/m² groups, n (%)

Variables	BMI < 25 kg/m² (n = 51)	BMI ≥ 25 kg/m² (n = 75)	χ²	P value
HBV DNA (IU/mL)			0.31	0.579
HBV > 2000	25 (49.02)	33 (44.00)
HBV ≤ 2000	26 (50.98)	42 (56.00)
HBe			2.05	0.152
Negative	32 (62.75)	56 (74.67)
Positive	19 (37.25)	19 (25.33)
Child-Pugh class			0.52	0.472
A	28 (54.90)	46 (61.33)
B	23 (45.10)	29 (38.67)
PVTT			3.12	0.077
No	26 (50.98)	50 (66.67)
Yes	25 (49.02)	25 (33.33)
BCLC stage			0.30	0.586
B	24 (47.06)	39 (52.00)
C	27 (52.94)	36 (48.00)
Metastasis			0.00	0.979
No	28 (54.90)	41 (54.67)
Yes	23 (45.10)	34 (45.33)
AFP (ng/mL)			3.01	0.083
> 1210	27 (52.94)	28 (37.33)
≤ 1210	24 (47.06)	47 (62.67)
Sex			0.97	0.323
Female	16 (31.37)	30 (40.00)
Male	35 (68.63)	45 (60.00)
Age (years)			1.00	0.316
< 60	26 (50.98)	45 (60.00)
≥ 60	25 (49.02)	30 (40.00)
ECOG			3.49	0.062
0-1	27 (52.94)	52 (69.33)
2	24 (47.06)	23 (30.67)
ALT (U/L)			1.14	0.286
> 40	26 (50.98)	31 (41.33)
≤ 40	25 (49.02)	44 (58.67)
Total bilirubin (μmol/L)			1.29	0.256
> 34	35 (68.63)	44 (58.67)
≤ 34	16 (31.37)	31 (41.33)
Diabetes			0.83	0.361
No	41 (80.39)	55 (73.33)
Yes	10 (19.61)	20 (26.67)
Hypertensive			0.11	0.736
No	15 (29.41)	20 (26.67)
Yes	36 (70.59)	55 (73.33)
Cirrhosis			0.18	0.675
No	28 (54.90)	44 (58.67)
Yes	23 (45.10)	31 (41.33)
Smoking			1.33	0.248
No	31 (60.78)	53 (70.67)
Yes	20 (39.22)	22 (29.33)
Alcohol			0.47	0.491
No	35 (68.63)	47 (62.67)
Yes	16 (31.37)	28 (37.33)
Interventional			0.84	0.358
No	25 (49.02)	43 (57.33)
Yes	26 (50.98)	32 (42.67)

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

Table 2 Tumor response between body mass index < 25 kg/m² and body mass index ≥ 25 kg/m² groups, n (%)

Variables	BMI < 25 kg/m² (n = 51)	BMI ≥ 25 kg/m² (n = 75)	χ²	P value
CR
0	51 (100.00)	73 (97.33)
1	0 (0.00)	1 (1.33)
PR
0	48 (94.12)	56 (74.67)
1	3 (5.88)	19 (25.33)
SD
0	34 (66.67)	49 (65.33)
1	17 (33.33)	26 (36.00)
PD
0	20 (39.22)	47 (62.67)
1	31 (60.78)	28 (37.33)
ORR			9.63	0.002
0	48 (94.12)	54 (72.00)
1	3 (5.88)	21 (28.00)
DCR			6.70	0.010
0	31 (60.78)	28 (37.33)
1	20 (39.22)	47 (64.00)

BMI: Body mass index. CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progression disease; ORR: Objective responds rates; DCR: Disease control rates.

Table 3 Cox subgroup analyses of the prognostic factors for progression-free survival and overall survival based on body mass index

BMI group	HR (95%CI)
Overall survival
18.5-24.9	1 (Reference)
25.0-29.9	0.48 (0.25-0.90)
≥ 30.0	0.28 (0.14-0.57)
P value	0.002
Progression-free survival
18.5-24.9	1 (Reference)
25.0-29.9	0.36 (0.19-0.69)
≥ 30.0	0.13 (0.06-0.31)
P value	< 0.001

BMI: Body mass index; HR: Hazard ratio; CI: Confidence interval.

Table 4 Univariate and multivariate analyses of the 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	1.11 (0.71-1.74)	0.642	-	-
Age (≥ 60 vs < 60), years	1.68 (1.09-2.60)	0.019	1.13 (0.70-1.83)	0.624
Alcohol (yes vs no)	0.94 (0.60-1.46)	0.784	-	-
ALT (> 40 vs ≤ 40), U/L	0.86 (0.56-1.30)	0.468	-	-
BCLC stage (C vs B)	1.85 (1.17-2.93)	0.008	2.60 (1.56-4.33)	< 0.001
BMI (normal vs overweight/obesity)	0.28 (0.15-0.52)	< 0.001	0.32 (0.17-0.59)	< 0.001
Child-Pugh score (B vs C)	2.71 (1.73-4.23)	< 0.001	2.30 (1.44-3.67)	< 0.001
Diabetes (yes vs no)	0.88 (0.53-1.49)	0.644	-	-
Cirrhosis (yes vs no)	0.98 (0.64-1.49)	0.922	-	-
ECOG (2 vs 0-1)	2.37 (1.50-3.72)	< 0.001	2.22 (1.37-3.61)	0.001
HBe (positive vs negative)	1.29 (0.82-2.03)	0.273	-	-
HBV-DNA (HBV ≤ 2000 vs HBV > 2000), IU/mL	1.27 (0.83-1.95)	0.276	-	-
Hypertensive (yes vs no)	1.10 (0.68-1.78)	0.709	-	-
PVTT (yes vs no)	1.06 (0.66-1.67)	0.820	-	-
Metastasis (yes vs no)	0.81 (0.53-1.23)	0.321	-	-
Sex (male vs female)	0.89 (0.58-1.35)	0.576	-	-
Smoking (yes vs no)	1.02 (0.65-1.61)	0.919	-	-
Total bilirubin (≤ 34 vs > 34), μmol/L	0.30 (0.18-0.50)	< 0.001	0.38 (0.21-0.67)	0.001
Interventional (yes vs no)	0.77 (0.48-1.22)	0.263	-	-

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

Table 5 Univariate and multivariate analyses of the 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	0.59 (0.36-0.95)	0.031	0.42 (0.25-0.72)	0.002
Age (≥ 60 vs < 60), years	0.70 (0.43-1.12)	0.139	-	-
Alcohol (yes vs no)	1.02 (0.64-1.63)	0.932	-	-
ALT (≤ 40 vs > 40), U/L	1.21 (0.77-1.92)	0.409	-	-
BCLC stage (C vs B)	0.59 (0.37-0.94)	0.028	0.43 (0.26-0.70)	0.001
BMI (normal vs overweight/obesity)	0.39 (0.21-0.70)	0.002	0.22 (0.11-0.45)	< 0.001
Child-Pugh score (B vs C)	0.77 (0.48-1.22)	0.266	-	-
Diabetes (yes vs no)	0.92 (0.52-1.60)	0.755	-	-
Cirrhosis (yes vs no)	1.15 (0.72-1.84)	0.562	-	-
ECOG (2 vs 0-1)	0.66 (0.40-1.07)	0.090	-	-
HBe (positive vs negative)	1.09 (0.67-1.78)	0.717	-	-
HBV-DNA (HBV ≤ 2000 vs HBV > 2000), IU/mL	0.67 (0.42-1.07)	0.091	-	-
Hypertensive (yes vs no)	1.20 (0.71-2.05)	0.494	-	-
PVTT (yes vs no)	2.36 (1.35-4.12)	0.003	2.23 (1.26-3.93)	0.006
Metastasis (yes vs no)	0.79 (0.50-1.26)	0.328	-	-
Sex (male vs female)	1.11 (0.70-1.77)	0.658	-	-
Smoking (yes vs no)	1.33 (0.81-2.19)	0.266	-	-
Total bilirubin (≤ 34 vs > 34), μmol/L	1.26 (0.78-2.02)	0.348	-	-
Interventional (yes vs no)	0.75 (0.47-1.19)	0.224	-	-

Table 6 Comparison of training set and validation set features, n (%)

Characteristic	Test (n = 38)	Train (n = 88)	χ²	P value
HBV DNA (IU/mL)			3.06	0.080
HBV > 2000	13 (34.21)	45 (51.14)
HBV ≤ 2000	25 (65.79)	43 (48.86)
HBe			0.38	0.537
Negative	28 (73.68)	60 (68.18)
Positive	10 (26.32)	28 (31.82)
Child-Pugh class			0.27	0.603
A	21 (55.26)	53 (60.23)
B	17 (44.74)	35 (39.77)
PVTT			2.62	0.106
No	27 (71.05)	49 (55.68)
Yes	11 (28.95)	39 (44.32)
BCLC stage			0.00	1.000
B	19 (50.00)	44 (50.00)
C	19 (50.00)	44 (50.00)
Metastasis			0.50	0.480
No	19 (50.00)	50 (56.82)
Yes	19 (50.00)	38 (43.18)
AFP (ng/mL)			0.03	0.872
> 1210	17 (44.74)	38 (43.18)
≤ 1210	21 (55.26)	50 (56.82)
Sex			1.34	0.247
Female	11 (28.95)	35 (39.77)
Male	27 (71.05)	53 (60.23)
BMI			0.02	0.880
≤ 25	15 (39.47)	36 (40.91)
> 25	23 (60.53)	52 (59.09)
Age (years)			1.78	0.182
< 60	18 (47.37)	53 (60.23)
≥ 60	20 (52.63)	35 (39.77)
ECOG			0.54	0.464
0-1	22 (57.89)	57 (64.77)
2	16 (42.11)	31 (35.23)
ALT (U/L)			0.22	0.642
> 40	16 (42.11)	41 (46.59)
≤ 40	22 (57.89)	47 (53.41)
Total bilirubin (μmol/L)			2.81	0.094
> 34	28 (73.68)	51 (57.95)
≤ 34	10 (26.32)	37 (42.05)
Diabetes			3.24	0.072
No	25 (65.79)	71 (80.68)
Yes	13 (34.21)	17 (19.32)
Hypertensive			1.12	0.289
No	13 (34.21)	22 (25.00)
Yes	25 (65.79)	66 (75.00)
Cirrhosis			0.01	0.911
No	22 (57.89)	50 (56.82)
Yes	16 (42.11)	38 (43.18)
Smoking			1.21	0.272
No	28 (73.68)	56 (63.64)
Yes	10 (26.32)	32 (36.36)
Alcohol			0.27	0.605
No	26 (68.42)	56 (63.64)
Yes	12 (31.58)	32 (36.36)
Interventional			0.94	0.332
No	23 (60.53)	45 (51.14)
Yes	15 (39.47)	43 (48.86)

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

Table 7 Treatment-related adverse events in patients with hepatocellular camrelizumab, n (%)

Variables	BMI < 25 kg/m² (n = 51)	BMI ≥ 25 kg/m² (n = 75)	χ²	P value
All grades: Rash	43 (84.31)	56 (74.67)	1.68	0.195
All grades: Nausea	26 (50.98)	30 (40.00)	1.48	0.223
All grades: Diarrhea	13 (25.49)	19 (25.33)	0.00	0.984
All grades: Fatigue	5 (9.80)	20 (26.67)	5.43	0.020
All grades: Myocarditis	3 (5.88)	9 (12.00)	0.70	0.401
All grades: Hyperbilirubinemia	9 (17.65)	10 (13.33)	0.44	0.507
All grades: Hypertension	4 (7.84)	10 (13.33)	0.93	0.336
All grades: Leukopenia	4 (7.84)	10 (13.33)	0.93	0.336
All grades: Thrombocytopenia	7 (13.73)	10 (13.33)	0.00	0.950
All grades: RCCEP	10 (19.61)	11 (14.67)	0.53	0.465
All grades: Neutropenia	4 (7.84)	10 (13.33)	0.93	0.336
All grades: Proteinuria	4 (7.84)	9 (12.00)	0.57	0.451
All grades: Hypothyroidism	5 (9.80)	8 (10.67)	0.02	0.876
All grades: Elevated ALT	6 (11.76)	10 (13.33)	0.07	0.795
All grades: Elevated AST	6 (11.76)	7 (9.33)	0.19	0.660
≥ 3 grades: Rash	5 (9.80)	10 (13.33)	0.36	0.548
≥ 3 grades: Nausea	2 (3.92)	6 (8.00)	0.30	0.583
≥ 3 grades: Diarrhea	0 (0.00)	4 (5.33)	1.34	0.247
≥ 3 grades: Fatigue	3 (5.88)	11 (14.67)	2.37	0.124
≥ 3 grades: Myocarditis	0 (0.00)	3 (4.00)	0.72	0.395
≥ 3 grades: Hyperbilirubinemia	0 (0.00)	3 (4.00)	0.72	0.395
≥ 3 grades: Hypertension	0 (0.00)	1 (1.33)	-	1.000
≥ 3 grades: Leukopenia	0 (0.00)	2 (2.67)	-	0.514
≥ 3 grades: Thrombocytopenia	0 (0.00)	2 (2.67)	-	0.514
≥ 3 grades: RCCEP	1 (1.96)	3 (4.00)	0.02	0.902
≥ 3 grades: Hypothyroidism	1 (1.96)	2 (2.67)	0.00	1.000
≥ 3 grades: Elevated ALT	1 (1.96)	3 (4.00)	0.02	0.902
≥ 3 grades: Elevated AST	3 (5.88)	4 (5.33)	0.00	1.000
≥ 3 grades: Neutropenia	0 (0.00)	0 (0.00)	-	-
≥ 3 grades: Proteinuria	0 (0.00)	0 (0.00)	-	-

BMI: Body mass index; RCCEP: Reactive cutaneous capillary endothelial proliferation; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Citation: Wang YQ, Pan D, Yao ZY, Li YQ, Qu PF, Wang RB, Gu QH, Jiang J, Han ZX, Liu HN. Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy. World J Gastroenterol 2024; 30(37): 4132-4148
URL: https://www.wjgnet.com/1007-9327/full/v30/i37/4132.htm
DOI: https://dx.doi.org/10.3748/wjg.v30.i37.4132