Transcatheter Interventional Therapy Combined with Targeted Immunotherapy versus Targeted Immunotherapy Alone in Patients with Unresectable Hepatocellular Carcinoma: A Meta-analysis

doi:10.3877/cma.j.issn.2095-5782.2026.03.001

Abstract

Abstract:

Objective

To evaluate the efficacy and safety of transcatheter interventional therapy combined with targeted and immune therapy versus targeted and immune therapy alone in the treatment of unresectable hepatocellular carcinoma.

Methods

A systematic review and meta-analysis conforming to PRISMA guidelines were conducted by searching the Cochrane Library, PubMed, and Embase databases up to January 2026. Relevant literature was collected, and two researchers conducted literature screening and quality assessment according to the inclusion and exclusion criteria. The meta-analysis was performed using RevMan 5.3.

Results

A total of 18 studies were included, involving 3 168 patients, with 1 794 in the combination therapy group and 1,374 in the single targeted-immunotherapy group. The combination therapy group showed higher complete response rate (OR=2.69, 95% CI: 1.45–4.99), objective response rate (OR=2.75, 95% CI: 2.35–3.22), and disease control rate (OR=2.61, 95% CI: 1.78–3.83), as well as longer progression-free survival (HR=0.56, 95% CI: 0.48–0.65) and overall survival (HR=0.5, 95% CI: 0.44–0.57). Regarding safety, the combination therapy group had significantly higher rates of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hyperbilirubinemia, nausea/vomiting, and abdominal pain.

Conclusion

The findings suggest that the transcatheter interventional therapy combined with targeted immunotherapy can improve the local control rate and long-term survival rate of unresectable HCC.

Key words: Hepatocellular carcinoma, Radiology, Interventional, Molecular Targeted Therapy, Immune Checkpoint Inhibitors, Meta-analysis

Tingxi Huang, Liujing Zhang, Wenle Tan, Qi Zhu, Feng Duan. Transcatheter Interventional Therapy Combined with Targeted Immunotherapy versus Targeted Immunotherapy Alone in Patients with Unresectable Hepatocellular Carcinoma: A Meta-analysis[J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2026, 14(03): 221-234.

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References 38

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研究	选择				可比性	结局			得分（总分9分）
研究	暴露队列的代表性（1分）	对照队列的选择（1分）	暴露的确定（1分）	研究开始时结局尚未发生（1分）	基于设计或分析所得的队列可比性（2分）	结局评估（1分）	随访时间足够长以观察到结局发生（1分）	队列随访的充分性（1分）	得分（总分9分）
Zhang,Hua等2024^[17]	1	1	1	1	2	1	1	1	9
Wu,Yang等2025^[18]	1	1	1	1	2	1	1	1	9
Lin,Chen等2025^[19]	1	1	1	1	2	1	1	1	9
Li,Wang等2024^[20]	1	1	1	1	2	1	0	1	8
Huang,Zhong等 2022^[21]	1	1	1	1	2	1	1	1	9
Chen,Wang等2025^[22]	1	1	1	1	2	1	1	1	9
Chen,Xu等2021^[23]	1	1	1	1	1	1	1	1	8
Yang,Deng等2023^[24]	1	1	1	1	2	1	0	1	8
Wang,Zhao等2023^[25]	1	1	1	1	2	1	0	1	8
Shen,Shao等2025^[26]	1	1	1	1	2	1	1	1	9
Pan,Ruan 等2025^[27]	1	1	1	1	2	1	1	1	9
Lei,Bai等2025^[28]	1	1	1	1	1	1	0	1	7
Yin,Li等2025^[29]	1	1	1	1	2	1	0	1	8
Wang,Zhang等2024^[30]	1	1	1	1	1	1	0	1	7
Mei,Tang等2021^[31]	1	1	1	1	1	1	0	1	7
Lou,Zhang等2025^[32]	1	1	1	1	1	1	0	1	7
Liu,Wang等2025^[33]	1	1	1	1	1	1	0	1	7
Diao,Wang等2024^[34]	1	1	1	1	1	1	1	1	8

研究	选择				可比性	结局			得分（总分9分）
研究	暴露队列的代表性（1分）	对照队列的选择（1分）	暴露的确定（1分）	研究开始时结局尚未发生（1分）	基于设计或分析所得的队列可比性（2分）	结局评估（1分）	随访时间足够长以观察到结局发生（1分）	队列随访的充分性（1分）	得分（总分9分）
Zhang,Hua等2024^[17]	1	1	1	1	2	1	1	1	9
Wu,Yang等2025^[18]	1	1	1	1	2	1	1	1	9
Lin,Chen等2025^[19]	1	1	1	1	2	1	1	1	9
Li,Wang等2024^[20]	1	1	1	1	2	1	0	1	8
Huang,Zhong等 2022^[21]	1	1	1	1	2	1	1	1	9
Chen,Wang等2025^[22]	1	1	1	1	2	1	1	1	9
Chen,Xu等2021^[23]	1	1	1	1	1	1	1	1	8
Yang,Deng等2023^[24]	1	1	1	1	2	1	0	1	8
Wang,Zhao等2023^[25]	1	1	1	1	2	1	0	1	8
Shen,Shao等2025^[26]	1	1	1	1	2	1	1	1	9
Pan,Ruan 等2025^[27]	1	1	1	1	2	1	1	1	9
Lei,Bai等2025^[28]	1	1	1	1	1	1	0	1	7
Yin,Li等2025^[29]	1	1	1	1	2	1	0	1	8
Wang,Zhang等2024^[30]	1	1	1	1	1	1	0	1	7
Mei,Tang等2021^[31]	1	1	1	1	1	1	0	1	7
Lou,Zhang等2025^[32]	1	1	1	1	1	1	0	1	7
Liu,Wang等2025^[33]	1	1	1	1	1	1	0	1	7
Diao,Wang等2024^[34]	1	1	1	1	1	1	1	1	8

研究	设计类型	治疗方案	例数	年龄（岁，例数/均数±标准差/中位数）	性别(男性/女性，例)	HBV(P/N，例)	Child-Pugh, A/B(例)	甲胎蛋白(<400/≥400，ng/mL)	VI(是/否，例)	肝外转移(是/否，例)	BCLC 分期, A/B/C(例)	CR, N [例(%)]	ORR,N [例(%)]	DCR, N [例(%)]	中位无进展生存期(月)	中位总生存期(月)
Zhang,Hua等2024 after PSM^[17]	回顾性多中心	TACE+TKI+ICI	54	≤60/>60(38/16)	46/8	53/1	54/0	26/28	22/32	19/35	0/23/31	1(1.9)	34(63.0)	46(85.2)	9.9	NR
		TKI+ICI	54	≤60/>60(37/17)	47/7	52/2	54/0	29/25	20/34	20/34	0/21/33	0(0.0)	16(29.6)	29(53.7)	5.8	18.5
Wu,Yang等2025 after PSM^[18]	回顾性多中心	HAIC+Lenvatinib+PD-1	66	<60/≥60(53/13)	63/3	62/4	58/8	24/42	66/0	21/45	0/0/66	0(0.0)	40(60.6)	63(95.4)	8.4	21.1
		Lenvatinib+PD-1	76	<60/≥60(62/14)	71/5	72/4	62/14	33/43	76/0	20/56	0/0/76	1(1.3)	22(28.9)	59(77.6)	5.6	11.5
Lin,Chen等2025 after PSM^[19]	回顾性多中心	Systemic+TACE	479	≤65/>65(265/214)	436/43	394/85	339/80	205/274	479/0	136/343	NA	15(0.3)	257(53.6)	391(81.6)	10.7	20.9
		Systemic alone	267	≤65/>65(142/125)	242/25	223/44	216/51	110/157	267/0	82/185	NA	0(0.0)	97(36.3）	172(64.4)	7.5	14.3
Li,Wang等2024 after ^[20]PSM	回顾性多中心	HAIC+Lenvatinib+PD1	81	≤60/>60(72/9)	68/13	NA	NA	27/54	67/14	38/43	0/11/70	4(4.9)	41(50.6)	57(70)	7.6	17.8
		Lenvatinib+PD-1	81	≤60/>60(68/13)	69/12	NA	NA	27/54	69/12	40/41	0/8/73	0(0.0)	21(25.9)	67(83)	5.6	13.9
Huang,Zhong等 2022 after PSM^[21]	回顾性单中心	TACE+ICIs+TKIs	24	58.0±10.7	20/4	20/4	18/6	12/12	18/6	9/15	0/0/24	1(4.2)	10(41.7)	19(79.2)	7.4	17.3
		ICIs+TKIs	24	56.5±14.0	21/3	20/4	14/10	15/9	18/6	13/11	0/0/24	0(0.0)	3(12.5)	12(50.0)	6.7	11.8
Chen .Wang等2025 after PSM^[22]	回顾性多中心	HAIC+Lenvatinib+PD-1	151	49±12	133/18	139/12	132/19	57/94	99/52	151/0	0/0/151	0(0.0)	72(47.7)	130(86.1)	7.6	26.0
		Lenvatinib+PD-1	151	49±12	131/20	138/13	132/19	55/96	97/54	151/0	0/0/151	0(0.0)	31(20.5)	109(72.2)	5.5	8.4
Chen,Xu等2021^[23]	回顾性多中心	Pembrolizumab+Lenvatinib+HAIC	84	52(42~67)	72/12	45/39	71/13	NA	49/35	20/64	0/22/62	13(15.5)	50(59.5)	74(88.1)	10.9	17.7
		Pembrolizumab+Lenvatinib	86	53(43~69)	71/15	48/38	75/11	NA	55/31	24/62	0/21/65	8(9.3)	36(41.9)	71(82.6)	6.8	12.6
Yang,Deng等2023 after PSM^[24]	回顾性单中心	Regorafenib+ICIs+TACE	23	53(43~65)	20/3	19/4	22/1	15/8	10/13	11/12	0/9/14	0(0.0)	8(34.8)	16(69.6)	5.8	15.0
		Regorafenib+ICIs	23	49(45~56)	19/4	16/7	18/5	14/9	8/15	12/11	0/5/18	0(0.0)	1(4.3)	10(43.5)	2.6	7.5
Wang,Zhao等2023 after PSM^[25]	回顾性单中心	TACE+Lenvatinib+ICIs	43	57.07±10.53	38/5	NA	35/8	25/18	19/24	22/21	0/8/35	0(0.0)	24(55.8)	37(86.0)	10.2	20.5
		Lenvatinib+ICIs	43	58.00±10.52	37/6	NA	33/10	21/22	18/25	25/18	0/7/36	0(0.0)	13(30.2)	28(65.1)	7.4	12.6
Shen,Shao等2025 after PSM^[26]	回顾性单中心	HAIT+Lenvatinib+PD-1	74	≤65/>65(61/13)	64/10	45/29	63/11	30/44	74/0	9/65	0/0/74	1(1.4)	28(37.8)	58(78.4)	10	19
		Lenvatinib+PD-1	74	≤65/>65(59/15)	64/10	46/28	64/10	25/49	74/0	8/66	0/0/74	1(1.4)	12(16.2)	35(47.3)	4	14
Pan,Ruan 等2025 after PSM^[27]	回顾性单中心	ICI+TKI+TACE	60	≥60/<60(42/18)	49/11	55/5	52/8	40/20	19/41	26/34	9/18/33	NA	10(16.6)	30(50)	8.4	26.9
		ICI+TKI	60	≥60/<60(47/13)	52/8	57/3	52/8	40/20	23/37	30/30	7/11/42	NA	13(21.6)	44(73)	6.6	24.2
Lei,Bai等2025^[28]	回顾性多中心	TACE+TKI+ICI	210	<65/≥65(187/23)	182/28	171/39	159/51	120/90	否	否	4/29/177	4(1.9)	86(56.7)	177(84.3)	8.4	14.5
		TKI+ICI	76	<65/≥65(62/14)	63/13	59/17	54/22	45/31	否	否	4/14/58	1(1.3)	16(21.1)	55(72.4)	4.0	10.0
Yin,Li等2025 after sIPTW^[29]	回顾性单中心	TACE-HAIC+Donafenib+ICIs	122	56.86±9.08	101/21	95/27	97/25	49/73	104/18	89/33	0/0/122	NA	83(68.4)	112(92.3)	16.4	29.4
		Targeted+ICIs	71	56.63±8.58	63/8	52/19	56/15	30/41	59/12	50/21	0/0/71	NA	20(28.0)	45(63.1)	10.0	18.0
Wang,Zhang等2024^[30]	回顾性单中心	HAIC+PD-1+TKIs	99	56.40±8.70	81/18	99/0	70/29	45/54	59/40	65/34	NA	0(0.0)	53(53.5)	94(94.9)	9.20	18.10
		PD-1+TKIs	95	57.11±8.60	78/17	95/0	72/23	51/44	57/38	71/24	NA	0(0.0)	30(31.6)	79(83.2)	6.33	12.57
Mei,Tang等2021^[31]	回顾性单中心	HAIC+PD-1+Lenvatinib	45	49.1±10.6	38/7	37/8	44/1	NA	36/9	15/30	0/5/40	0(0.0)	18(40.0)	38(77.6)	8.8	15.9
		PD-1+Lenvatinib	25	50.1±12.3	18/7	19/6	22/3	NA	18/7	13/12	0/3/22	0(0.0)	4(16.0)	11(44.0)	5.4	8.6
Lou,Zhang等2025^[32]	回顾性单中心	HAIC+Lenvatinib+PD-1	67	56.15±7.78	61/6	59/8	56/11	<1000/≥1000: 34/33	41/26	49/27	0/0/67	3(4.5)	46(68.7)	62(92.5)	13.8	22.2
		Lenvatinib+PD-1	48	53.48±10.39	44/4	36/12	37/11	28/20	26/22	36/13	0/0/48	1(2.1)	18(37.5)	36(75.0)	5.1	14.4
Liu,Wang等2025^[33]	回顾性单中心	TACE+ICI+anti-VEGF/TKI	54	61(55~66)	42/12	44/10	44/10	≤200/>200: 33/21	37/17	25/29	0/0/54	NA	NA	NA	14.7	18.3
		ICI+anti-VEGF/TKI	57	60(50~66)	48/9	37/20	48/9	27/30	39/18	34/23	0/0/57	NA	NA	NA	11.2	11.8
Diao,Wang等2024^[34]	回顾性单中心	HAIC+Lenvatinib+ICI	58	≤50/>50(16/52)	49/9	47/11	49/9	28/30	32/26	19/39	0/24/34	1(1.7)	28(48.3)	51(87.9)	13.0	24.0
		Lenvatinib+ICI	63	≤50/>50(5/27)	50/13	52/11	55/8	31/32	30/33	21/42	0/25/38	0(0.0)	15(23.8)	44(69.8)	7.2	13.0

研究	设计类型	治疗方案	例数	年龄（岁，例数/均数±标准差/中位数）	性别(男性/女性，例)	HBV(P/N，例)	Child-Pugh, A/B(例)	甲胎蛋白(<400/≥400，ng/mL)	VI(是/否，例)	肝外转移(是/否，例)	BCLC 分期, A/B/C(例)	CR, N [例(%)]	ORR,N [例(%)]	DCR, N [例(%)]	中位无进展生存期(月)	中位总生存期(月)
Zhang,Hua等2024 after PSM^[17]	回顾性多中心	TACE+TKI+ICI	54	≤60/>60(38/16)	46/8	53/1	54/0	26/28	22/32	19/35	0/23/31	1(1.9)	34(63.0)	46(85.2)	9.9	NR
		TKI+ICI	54	≤60/>60(37/17)	47/7	52/2	54/0	29/25	20/34	20/34	0/21/33	0(0.0)	16(29.6)	29(53.7)	5.8	18.5
Wu,Yang等2025 after PSM^[18]	回顾性多中心	HAIC+Lenvatinib+PD-1	66	<60/≥60(53/13)	63/3	62/4	58/8	24/42	66/0	21/45	0/0/66	0(0.0)	40(60.6)	63(95.4)	8.4	21.1
		Lenvatinib+PD-1	76	<60/≥60(62/14)	71/5	72/4	62/14	33/43	76/0	20/56	0/0/76	1(1.3)	22(28.9)	59(77.6)	5.6	11.5
Lin,Chen等2025 after PSM^[19]	回顾性多中心	Systemic+TACE	479	≤65/>65(265/214)	436/43	394/85	339/80	205/274	479/0	136/343	NA	15(0.3)	257(53.6)	391(81.6)	10.7	20.9
		Systemic alone	267	≤65/>65(142/125)	242/25	223/44	216/51	110/157	267/0	82/185	NA	0(0.0)	97(36.3）	172(64.4)	7.5	14.3
Li,Wang等2024 after ^[20]PSM	回顾性多中心	HAIC+Lenvatinib+PD1	81	≤60/>60(72/9)	68/13	NA	NA	27/54	67/14	38/43	0/11/70	4(4.9)	41(50.6)	57(70)	7.6	17.8
		Lenvatinib+PD-1	81	≤60/>60(68/13)	69/12	NA	NA	27/54	69/12	40/41	0/8/73	0(0.0)	21(25.9)	67(83)	5.6	13.9
Huang,Zhong等 2022 after PSM^[21]	回顾性单中心	TACE+ICIs+TKIs	24	58.0±10.7	20/4	20/4	18/6	12/12	18/6	9/15	0/0/24	1(4.2)	10(41.7)	19(79.2)	7.4	17.3
		ICIs+TKIs	24	56.5±14.0	21/3	20/4	14/10	15/9	18/6	13/11	0/0/24	0(0.0)	3(12.5)	12(50.0)	6.7	11.8
Chen .Wang等2025 after PSM^[22]	回顾性多中心	HAIC+Lenvatinib+PD-1	151	49±12	133/18	139/12	132/19	57/94	99/52	151/0	0/0/151	0(0.0)	72(47.7)	130(86.1)	7.6	26.0
		Lenvatinib+PD-1	151	49±12	131/20	138/13	132/19	55/96	97/54	151/0	0/0/151	0(0.0)	31(20.5)	109(72.2)	5.5	8.4
Chen,Xu等2021^[23]	回顾性多中心	Pembrolizumab+Lenvatinib+HAIC	84	52(42~67)	72/12	45/39	71/13	NA	49/35	20/64	0/22/62	13(15.5)	50(59.5)	74(88.1)	10.9	17.7
		Pembrolizumab+Lenvatinib	86	53(43~69)	71/15	48/38	75/11	NA	55/31	24/62	0/21/65	8(9.3)	36(41.9)	71(82.6)	6.8	12.6
Yang,Deng等2023 after PSM^[24]	回顾性单中心	Regorafenib+ICIs+TACE	23	53(43~65)	20/3	19/4	22/1	15/8	10/13	11/12	0/9/14	0(0.0)	8(34.8)	16(69.6)	5.8	15.0
		Regorafenib+ICIs	23	49(45~56)	19/4	16/7	18/5	14/9	8/15	12/11	0/5/18	0(0.0)	1(4.3)	10(43.5)	2.6	7.5
Wang,Zhao等2023 after PSM^[25]	回顾性单中心	TACE+Lenvatinib+ICIs	43	57.07±10.53	38/5	NA	35/8	25/18	19/24	22/21	0/8/35	0(0.0)	24(55.8)	37(86.0)	10.2	20.5
		Lenvatinib+ICIs	43	58.00±10.52	37/6	NA	33/10	21/22	18/25	25/18	0/7/36	0(0.0)	13(30.2)	28(65.1)	7.4	12.6
Shen,Shao等2025 after PSM^[26]	回顾性单中心	HAIT+Lenvatinib+PD-1	74	≤65/>65(61/13)	64/10	45/29	63/11	30/44	74/0	9/65	0/0/74	1(1.4)	28(37.8)	58(78.4)	10	19
		Lenvatinib+PD-1	74	≤65/>65(59/15)	64/10	46/28	64/10	25/49	74/0	8/66	0/0/74	1(1.4)	12(16.2)	35(47.3)	4	14
Pan,Ruan 等2025 after PSM^[27]	回顾性单中心	ICI+TKI+TACE	60	≥60/<60(42/18)	49/11	55/5	52/8	40/20	19/41	26/34	9/18/33	NA	10(16.6)	30(50)	8.4	26.9
		ICI+TKI	60	≥60/<60(47/13)	52/8	57/3	52/8	40/20	23/37	30/30	7/11/42	NA	13(21.6)	44(73)	6.6	24.2
Lei,Bai等2025^[28]	回顾性多中心	TACE+TKI+ICI	210	<65/≥65(187/23)	182/28	171/39	159/51	120/90	否	否	4/29/177	4(1.9)	86(56.7)	177(84.3)	8.4	14.5
		TKI+ICI	76	<65/≥65(62/14)	63/13	59/17	54/22	45/31	否	否	4/14/58	1(1.3)	16(21.1)	55(72.4)	4.0	10.0
Yin,Li等2025 after sIPTW^[29]	回顾性单中心	TACE-HAIC+Donafenib+ICIs	122	56.86±9.08	101/21	95/27	97/25	49/73	104/18	89/33	0/0/122	NA	83(68.4)	112(92.3)	16.4	29.4
		Targeted+ICIs	71	56.63±8.58	63/8	52/19	56/15	30/41	59/12	50/21	0/0/71	NA	20(28.0)	45(63.1)	10.0	18.0
Wang,Zhang等2024^[30]	回顾性单中心	HAIC+PD-1+TKIs	99	56.40±8.70	81/18	99/0	70/29	45/54	59/40	65/34	NA	0(0.0)	53(53.5)	94(94.9)	9.20	18.10
		PD-1+TKIs	95	57.11±8.60	78/17	95/0	72/23	51/44	57/38	71/24	NA	0(0.0)	30(31.6)	79(83.2)	6.33	12.57
Mei,Tang等2021^[31]	回顾性单中心	HAIC+PD-1+Lenvatinib	45	49.1±10.6	38/7	37/8	44/1	NA	36/9	15/30	0/5/40	0(0.0)	18(40.0)	38(77.6)	8.8	15.9
		PD-1+Lenvatinib	25	50.1±12.3	18/7	19/6	22/3	NA	18/7	13/12	0/3/22	0(0.0)	4(16.0)	11(44.0)	5.4	8.6
Lou,Zhang等2025^[32]	回顾性单中心	HAIC+Lenvatinib+PD-1	67	56.15±7.78	61/6	59/8	56/11	<1000/≥1000: 34/33	41/26	49/27	0/0/67	3(4.5)	46(68.7)	62(92.5)	13.8	22.2
		Lenvatinib+PD-1	48	53.48±10.39	44/4	36/12	37/11	28/20	26/22	36/13	0/0/48	1(2.1)	18(37.5)	36(75.0)	5.1	14.4
Liu,Wang等2025^[33]	回顾性单中心	TACE+ICI+anti-VEGF/TKI	54	61(55~66)	42/12	44/10	44/10	≤200/>200: 33/21	37/17	25/29	0/0/54	NA	NA	NA	14.7	18.3
		ICI+anti-VEGF/TKI	57	60(50~66)	48/9	37/20	48/9	27/30	39/18	34/23	0/0/57	NA	NA	NA	11.2	11.8
Diao,Wang等2024^[34]	回顾性单中心	HAIC+Lenvatinib+ICI	58	≤50/>50(16/52)	49/9	47/11	49/9	28/30	32/26	19/39	0/24/34	1(1.7)	28(48.3)	51(87.9)	13.0	24.0
		Lenvatinib+ICI	63	≤50/>50(5/27)	50/13	52/11	55/8	31/32	30/33	21/42	0/25/38	0(0.0)	15(23.8)	44(69.8)	7.2	13.0

结局指标	纳入文献数	I²	OR/HR(95% CI)	Egger检验	Begg检验
CR	10	0%	2.69(1.45~4.99)	0.454 6	0.420 8
ORR	17	30%	2.75(2.35~3.22)	0.103 6	0.117 5
DCR	17	73%	2.61(1.78~3.83)	0.410 7	0.138 1
PFS	16	65%	0.56(0.48~0.65)	0.019 9	0.005 2
OS	18	42%	0.50(0.44~0.57)	0.092 4	0.102 9

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