Effect of fatty liver disease on clinical efficacy and prognosis of systemic treatment for advanced ICC

doi:10.3877/cma.j.issn.2095-3232.2026.02.013

Abstract

Abstract:

Objective

To evaluate the effect of fatty liver disease (FLD) on clinical efficacy and prognosis of immunotherapy-based systemic treatment for advanced intrahepatic cholangiocarcinoma (ICC).

Methods

Clinicopathological data of 54 patients with advanced ICC receiving immunotherapy-based systematic treatment in Zhangjiagang Hospital Affiliated to Soochow University from April 2019 to April 2022 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 21 patients were male and 33 female, aged from 29 to 77 years, with a median age of 58 years. All patients were divided into the FLD group (n=24) and non-FLD group (n=30). Clinical efficacy was evaluated by Response Evaluation Criteria In Solid Tumours (RECIST). The objective remission rate (ORR) and adverse event (AE) between two groups were compared by Chi-square test. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method and Log-rank test. Prognostic factors were analyzed and evaluated by Cox's regression model.

Results

The ORR of all patients in this study was 22%(12/54), and 8%(2/24) in the FLD group, significantly lower than 33%(10/30) in the non-FLD group (χ²=18.793, P<0.001). The incidence of AE in the FLD group was 75%(18/24), significantly higher than 37%(11/30) in the non-FLD group (χ²=7.880, P=0.005). The incidence of grade 1-2 AE in the FLD group was 50%(12/24), significantly higher than 20%(6/30) in the non-FLD group (χ²=5.400, P=0.020). However, no significant difference was observed in the incidence of grade 3-4 AE between two groups (χ²=0.571, P=0.450). The median OS was 22.7 months and the median PFS was 5.8 months. The median OS was 11.7 and 27.3 months, and the median PFS was 4.4 and 8.3 months in the FLD and non-FLD groups, respectively. The OS and PFS in the FLD group were significantly shorter than those in the non-FLD group (χ²=14.967, 4.527; both P<0.05). Univariate Cox's analysis showed that FLD, ALB, immunoglobulin (Ig) G and IgM were the influencing factors of OS in ICC patients (HR=11.320, 6.176, 4.877, 6.452; all P<0.05). Multivariate Cox's analysis showed that FLD (HR=6.569, 95%CI: 1.407-30.680; P=0.017) and IgM<2.2 g/L (HR=3.914, 95%CI: 1.130-13.560; P=0.031) were the independent risk factor of OS.

Conclusions

FLD significantly reduces clinical efficacy of immunotherapy-based systemic therapy and shortens the survival time in patients with advanced ICC, suggesting that the influence of FLD on immunotherapy should be considered in clinical practice, thereby adjusting the treatment strategy.

Key words: Intrahepatic cholangiocarcinoma, Fatty liver disease, Systemic therapy, Immunotherapy

Chen Wang, Fang Xu, Fang Zhou, Jin Liu, Fang Sheng. Effect of fatty liver disease on clinical efficacy and prognosis of systemic treatment for advanced ICC[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 226-233.

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Figures/Tables 5

变量	非FLD组	FLD组	统计值	P值
性别(例, 男/女)	12/18	9/15	χ²=0.035	0.851
年龄(岁, $x ¯$ ±s)	54±11	63±10	t=-3.155	0.003
高血压[例(%)]	4(13)	5(21)	-	0.489
糖尿病[例(%)]	2 (7)	8 (33)	-	0.016
腹水[例(%)]	3 (10)	2 (8)	-	>0.999
Child-Pugh分级A级[例(%)]	5 (17)	0 (0)	-	0.059
ECOG-PS评分0分[例(%)]	26 (87)	21 (88)	-	>0.999
HBV感染[例(%)]	11 (37)	8 (33)	χ²=0.065	0.799
CA19-9[kU/L, M(Q₁, Q₃)]	46 (18, 311)	62 (10, 355)	Z=-0.501	0.616
TB [μmol/L, M(Q₁, Q₃)]	11 (8, 15)	12 (10, 20)	Z=-1.260	0.208
ALT[U/L, M(Q₁, Q₃)]	25 (16, 47)	50(34, 74)	Z=-2.507	0.012
ALB[g/L, M(Q₁, Q₃)]	42 (40, 43)	37 (35, 39)	Z=3.447	0.001
WBC[×10⁹/L, M(Q₁, Q₃)]	6.7 (4.9, 7.9)	7.2 (5.6, 9.3)	Z=-1.010	0.313
淋巴细胞[×10⁹/L, M(Q₁, Q₃)]	2.1 (1.4, 2.4)	1.2 (1.0, 1.7)	Z=3.628	<0.001
IgG[g/L, M(Q₁, Q₃)]	13.8 (9.5, 15.2)	23.8 (18.5, 28.3)	Z=-5.520	<0.001
IgA[g/L, M(Q₁, Q₃)]	3.4 (2.5, 4.6)	4.6 (3.9, 6.0)	Z=-3.238	0.001
IgM[g/L, M(Q₁, Q₃)]	1.8 (1.4, 2.3)	2.3 (1.7, 2.8)	Z=-1.776	0.076
CD4/CD8[M(Q₁, Q₃)]	3.8 (3.7, 3.9)	4.0 (3.9, 4.1)	Z=-3.708	<0.001
肿瘤最大直径(mm, $x ¯$ ±s)	56±25	71±32	t=-1.520	0.139
淋巴结转移[例(%)]	23 (77)	18 (75)	χ²=0.020	0.887
肿瘤远处转移[例(%)]	16 (53)	11 (46)	χ²=0.300	0.584
门静脉癌栓[例(%)]	3 (10)	3 (13)	-	>0.999

变量	非FLD组	FLD组	统计值	P值
性别(例, 男/女)	12/18	9/15	χ²=0.035	0.851
年龄(岁, $x ¯$ ±s)	54±11	63±10	t=-3.155	0.003
高血压[例(%)]	4(13)	5(21)	-	0.489
糖尿病[例(%)]	2 (7)	8 (33)	-	0.016
腹水[例(%)]	3 (10)	2 (8)	-	>0.999
Child-Pugh分级A级[例(%)]	5 (17)	0 (0)	-	0.059
ECOG-PS评分0分[例(%)]	26 (87)	21 (88)	-	>0.999
HBV感染[例(%)]	11 (37)	8 (33)	χ²=0.065	0.799
CA19-9[kU/L, M(Q₁, Q₃)]	46 (18, 311)	62 (10, 355)	Z=-0.501	0.616
TB [μmol/L, M(Q₁, Q₃)]	11 (8, 15)	12 (10, 20)	Z=-1.260	0.208
ALT[U/L, M(Q₁, Q₃)]	25 (16, 47)	50(34, 74)	Z=-2.507	0.012
ALB[g/L, M(Q₁, Q₃)]	42 (40, 43)	37 (35, 39)	Z=3.447	0.001
WBC[×10⁹/L, M(Q₁, Q₃)]	6.7 (4.9, 7.9)	7.2 (5.6, 9.3)	Z=-1.010	0.313
淋巴细胞[×10⁹/L, M(Q₁, Q₃)]	2.1 (1.4, 2.4)	1.2 (1.0, 1.7)	Z=3.628	<0.001
IgG[g/L, M(Q₁, Q₃)]	13.8 (9.5, 15.2)	23.8 (18.5, 28.3)	Z=-5.520	<0.001
IgA[g/L, M(Q₁, Q₃)]	3.4 (2.5, 4.6)	4.6 (3.9, 6.0)	Z=-3.238	0.001
IgM[g/L, M(Q₁, Q₃)]	1.8 (1.4, 2.3)	2.3 (1.7, 2.8)	Z=-1.776	0.076
CD4/CD8[M(Q₁, Q₃)]	3.8 (3.7, 3.9)	4.0 (3.9, 4.1)	Z=-3.708	<0.001
肿瘤最大直径(mm, $x ¯$ ±s)	56±25	71±32	t=-1.520	0.139
淋巴结转移[例(%)]	23 (77)	18 (75)	χ²=0.020	0.887
肿瘤远处转移[例(%)]	16 (53)	11 (46)	χ²=0.300	0.584
门静脉癌栓[例(%)]	3 (10)	3 (13)	-	>0.999

变量	非FLD组	FLD组	χ²值	P值
治疗方案			0.855	0.652
免疫+靶向+化疗	21 (70)	14 (58)
免疫+靶向	4 (13)	5 (21)
免疫+化疗	5 (17)	5 (21)
RECIST评价			5.584	0.134
PD	5 (17)	8 (33)
SD	15 (50)	14 (58)
PR	9 (30)	2 (8)
CR	1 (3)	0 (0)
AE	11 (37)	18 (75)	7.880	0.005
1~2级	6 (20)	12 (50)	5.400	0.020
3~4级	5 (17)	6 (25)	0.571	0.450

变量	单因素分析		多因素分析
变量	HR(95%CI)	P值	HR (95%CI)	P值
FLD	11.320 (2.477~51.700)	0.002	6.569(1.407~30.680)	0.017
ALB<35 g/L	6.176 (2.224~17.150)	<0.001	1.511(0.461~4.950)	0.495
IgG<17.4 g/L	4.877 (1.808~13.150)	0.002	2.080(0.724~5.979)	0.174
IgM<2.2 g/L	6.452 (2.117~19.660)	0.001	3.914(1.130~13.560)	0.031

变量	单因素分析		多因素分析
变量	HR(95%CI)	P值	HR (95%CI)	P值
腹水	5.106 (1.607~16.220)	0.006	2.955 (0.283~30.830)	0.365
ECOG-PS评分	3.039 (1.110~8.318)	0.030	1.642 (0.209~12.890)	0.637
FLD	2.196 (1.045~4.614)	0.038	1.692 (0.700~4.091)	0.243
ALB<35 g/L	2.411 (1.019~5.703)	0.045	1.314 (0.464~3.721)	0.606
IgG<17.4 g/L	2.107 (1.026~4.327)	0.042	2.394 (0.953~6.014)	0.063
肿瘤远处转移	1.799 (0.898~3.605)	0.098	2.871 (1.284~6.422)	0.010

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