Comparison of the efficacy of transarterial chemoembolization combined with different molecular targeted agents and/or immune checkpoint inhibitors for unresectable hepatocellular carcinoma: a systematic review and network meta-analysis

Introduction

In 2022, there were approximately 865,000 new cases of liver cancer (LC) and 758,000 LC-related deaths worldwide, making LC the sixth most common malignancy and the third leading cause of cancer-related mortality globally (1). Hepatocellular carcinoma (HCC) accounts for approximately 75–95% of all LC cases (2). However, because HCC often has an insidious onset, lacks obvious early symptoms, and progresses rapidly, about 70% of patients are already at an intermediate or advanced stage at diagnosis, losing the opportunity for curative resection (3).

For unresectable HCC (uHCC), transarterial chemoembolization (TACE) is an important standard treatment, particularly for patients with intermediate-stage disease (4). TACE works by selectively catheterizing the tumor-feeding artery and delivering chemotherapeutic agents together with embolic materials into the tumor vascular bed, thereby achieving both local high-concentration chemotherapy and ischemic necrosis, and ultimately controlling the tumor locally. Due to its strong local antitumor effect, minimal invasiveness, and repeatability, TACE has been widely used in clinical practice.

However, although TACE alone can prolong survival to some extent, it has several limitations, including a high rate of local recurrence, an increased risk of distant metastasis, and unsatisfactory long-term prognosis. One of the key mechanisms is that TACE can significantly upregulate hypoxia-inducible factor-1alpha (HIF-1alpha), thereby promoting the expression of multiple pro-angiogenic signals such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) (5). This process induces tumor neovascularization, re-establishes tumor blood supply, and creates a favorable microenvironment for the growth and metastasis of residual tumor cells (6). In this context, how to preserve the local tumor-control advantage of TACE while inhibiting the pro-angiogenic and microenvironment-remodeling effects induced by TACE has become a key issue in optimizing the comprehensive treatment strategy for uHCC.

In recent years, with a deeper understanding of the molecular mechanisms underlying HCC development and the tumor immune microenvironment, molecular targeted agents (MTAs), represented by tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs), represented by programmed cell death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1), have successively emerged. As a result, the previously difficult treatment landscape for uHCC has been transformed. MTAs inhibit key signaling pathways such as VEGFRs and PDGFRs, thereby blocking tumor angiogenesis and providing an opportunity to counteract the “revascularization” induced by TACE. ICIs restore and enhance antitumor immune responses by relieving tumor-mediated suppression of the host immune system and reactivating exhausted T cells, offering hope for improving survival in patients with intermediate and advanced HCC. Multiple studies have shown that TACE combined with MTAs and/or ICIs can improve overall survival (OS) and progression-free survival (PFS) (7,8).

Although numerous TACE-based combination regimens have been explored, including combinations with different MTAs and/or ICIs, direct head-to-head comparisons among these regimens remain limited. Therefore, this study aimed to conduct a network meta-analysis (NMA) to compare the differences in efficacy among TACE combined with different MTAs and/or ICIs. We present this article in accordance with the PRISMA-NMA reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0436/rc) (9).

Methods

Search strategy

We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science. The search period extended from the inception of each database to February 26, 2026. The search strategy combined subject headings and free-text terms. The core search terms included “hepatocellular carcinoma”, “transarterial chemoembolization”, “sorafenib”, “anlotinib”, “lenvatinib”, “sunitinib”, “apatinib”, “orantinib”, “brivanib”, “donafenib”, “atezolizumab”, “durvalumab”, “camrelizumab”, “pembrolizumab”, “tislelizumab”, and “sintilimab”. Detailed search strategies were provided in Table S1. This NMA was registered in PROSPERO under the registration number CRD420261350164.

Eligibility criteria

The inclusion criteria were developed according to the PICOS framework as follows: (I) patients diagnosed with uHCC by pathology or imaging; (II) the intervention group received TACE combined with MTAs and/or ICIs; (III) the control group received TACE combined with other MTAs and/or ICIs, TACE alone, or MTAs and/or ICIs alone; (IV) the primary outcome measures were OS and PFS; and the secondary outcomes were objective response rate (ORR) and disease control rate (DCR); and (V) the study design was a randomized controlled trial (RCT) or cohort study.

The exclusion criteria were as follows: (I) patients had received other anticancer treatments before the study; (II) valid data could not be extracted; (III) the study was a single-arm study; (IV) the study was a case report; or (V) the study was a systematic review or meta-analysis.

Data extraction and quality assessment

Data from the included studies were independently extracted by two investigators (J.Y.L. and X.H.W.). Any discrepancies were resolved through discussion with a third investigator (Y.L.). The extracted information included the first author, year of publication, study design, sample size, sex distribution, mean age, treatment regimens, and reported outcomes.

For cohort studies and RCTs, study quality was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias tool, respectively. The NOS consists of three domains and eight items, with a maximum score of 9 points (10). Scores of 0–3, 4–6, and 7–9 were defined as low, moderate, and high quality, respectively. The Cochrane Risk of Bias tool evaluates bias across seven domains, with each domain rated as low, high, or unclear risk of bias (11).

Statistical analysis

For OS and PFS, hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted. For studies that did not directly report these data, survival information was extracted from Kaplan-Meier curves using Engauge Digitizer version 11.3 and converted into HR and 95% CIs. For ORR and DCR, pooled odds ratios (ORs) and corresponding 95% CIs were used for comparison.

Statistical analyses were performed using R software (version 4.3.1) and Stata 14.0. Based on a random-effects model, a frequentist framework was used for the NMA. First, a network plot was constructed to integrate direct and indirect evidence across treatment regimens involving TACE combined with different MTAs and/or ICIs. Second, a global inconsistency test was performed to assess the consistency of the entire network evidence structure. If the result was not significant, a consistency model was used to pool the effect estimates. Third, local inconsistency was assessed using node-splitting analysis to evaluate each closed loop in the network and identify specific sources of inconsistency. Fourth, based on the pooled results, P-scores were calculated to quantify the relative efficacy ranking of each intervention in the network; P-scores range from 0 to 1, with higher values indicating a greater likelihood of superior efficacy (12). Finally, publication bias was assessed using comparison-adjusted funnel plots combined with Egger’s test (13). A two-sided P value <0.05 was considered statistically significant.

Results

The studies included in the NMA

A total of 9,327 records were identified through searches of the relevant databases. After removing duplicates, 6,203 records remained. Following title and abstract screening, 5,758 records were excluded, leaving 445 articles for full-text review. Of these, 27 articles were excluded because the full text could not be obtained, and 418 articles were ultimately assessed in full. A further 310 articles were excluded, mainly because the interventions or comparators did not meet the inclusion criteria, the outcome measures were not relevant, the study design or study population were not eligible, the data were incomplete, or the publication was duplicated. Finally, 108 articles were included in the NMA (14-121). The study selection process is shown in Figure 1.

Figure 1 Selection process for the studies included in the network meta-analysis.

A total of 26 treatment regimens were included in this NMA, namely: TACE, TACE + brivanib (TACE + Bri), TACE + sorafenib + sintilimab (TACE + Sor + Sin), apatinib + camrelizumab (Apa + Cam), TACE + Apa + Cam, TACE + Apa, Sor, TACE + Sor, TACE + donafenib + toripalimab (TACE + Don + Tor), TACE + Sor + Cam, TACE + sunitinib (TACE + Sun), TACE + orantinib (TACE + Ora), TACE + lenvatinib + tislelizumab (TACE + Len + Tis), TACE + atezolizumab + bevacizumab (TACE + Ate + Bev), TACE + Ate, Ate + Bev, Len, TACE + Len, TACE + Don, TACE + Len + pembrolizumab (TACE + Len + Pem), TACE + Len + Cam, TACE + Cam, TACE + durvalumab (TACE + Dur), TACE + Dur + Bev, TACE + anlotinib + sintilimab (TACE + Anl + Sin), and TACE + anlotinib (TACE + Anl). The characteristics of the included studies are presented in Table S2.

Among the included studies, 84 were retrospective cohort studies, and 24 were RCTs. A total of 19,761 patients were involved, with mean ages ranging from 45.8 to 79 years. The quality assessment of the included studies is shown in Tables S3,S4. The overall methodological quality of the included studies was generally acceptable.

Evidence network geometry

The treatment networks for OS, PFS, ORR, and DCR were generally characterized by a TACE-centered structure, in which most regimens were connected to the network through comparisons with TACE alone, whereas direct head-to-head comparisons between active combination regimens were relatively limited. As a result, many comparisons among combination strategies were informed partly or predominantly by indirect evidence. In general, conventional regimens such as TACE alone, TACE + Sor, and TACE + Len were supported by broader evidence bases, whereas several triple-combination regimens were represented by fewer studies and smaller sample sizes. The number of studies and patients contributing to each treatment node across the OS, PFS, ORR, and DCR networks is summarized in Table S5.

OS

For OS, 23 treatment regimens were included (Figure 2A). Compared with TACE, several triple-combination regimens showed significant OS benefit, including TACE + Anl + Sin, TACE + Don + Tor, TACE + Len + Tis, TACE + Sor + Cam, TACE + Apa + Cam, TACE + Len + Cam, and TACE + Len + Pem (Figure 2B,2C). According to the P-score ranking, TACE + Anl + Sin had the highest probability of being the best treatment option for OS (P-score =0.937), followed by TACE + Don + Tor (P-score =0.915), TACE + Len + Tis (P-score =0.884), TACE + Sor + Cam (P-score =0.880), and TACE + Apa + Cam (P-score =0.768) (Figure 2D).

Figure 2 Network meta-analysis of overall survival. (A) Network plot. Nodes represent different interventions, and the size of each node is proportional to the sample size or number of studies included for the corresponding treatment. Lines indicate direct comparisons between two interventions, and the thickness of each line is proportional to the number of studies for that direct comparison. (B) Forest plot of each treatment relative to TACE. Squares represent effect size estimates, horizontal lines indicate 95% CIs, and the vertical line represents the line of no effect. (C) League table of pairwise comparisons among all treatments. (D) Bar chart of the P-score values for all treatments. A P-score closer to 1 indicates a higher ranking in overall therapeutic efficacy. Anl, anlotinib; Apa, apatinib; Ate, atezolizumab; Bev, bevacizumab; Bri, brivanib; Cam, camrelizumab; CI, confidence interval; Don, donafenib; HR, hazard ratio; Len, lenvatinib; Ora, orantinib; Pem, pembrolizumab; Sin, sintilimab; Sor, sorafenib; Sun, sunitinib; TACE, transarterial chemoembolization; Tis, tislelizumab; Tor, toripalimab.

PFS

For PFS, 26 treatment regimens were included (Figure 3A). Compared with TACE, several triple-combination regimens showed significant PFS benefit, including TACE + Anl + Sin, TACE + Apa + Cam, TACE + Ate + Bev, TACE + Don + Tor, TACE + Dur + Bev, TACE + Len + Cam, TACE + Len + Pem, TACE + Len + Tis, TACE + Sor + Cam significantly improved PFS in patients (Figure 3B,3C).

Figure 3 Network meta-analysis of progression-free survival. (A) Network plot. Nodes represent different interventions, and the size of each node is proportional to the sample size or number of studies included for the corresponding treatment. Lines indicate direct comparisons between two interventions, and the thickness of each line is proportional to the number of studies for that direct comparison. (B) Forest plot of each treatment relative to TACE. Squares represent effect size estimates, horizontal lines indicate 95% CIs, and the vertical line represents the line of no effect. (C) League table of pairwise comparisons among all treatments. (D) Bar chart of the P-score values for all treatments. A P-score closer to 1 indicates a higher ranking in overall therapeutic efficacy. Anl, anlotinib; Apa, apatinib; Ate, atezolizumab; Bev, bevacizumab; Bri, brivanib; Cam, camrelizumab; CI, confidence interval; Don, donafenib; HR, hazard ratio; Len, lenvatinib; Ora, orantinib; Pem, pembrolizumab; Sin, sintilimab; Sor, sorafenib; Sun, sunitinib; TACE, transarterial chemoembolization; Tis, tislelizumab; Tor, toripalimab.

According to the P-score ranking, TACE + Len + Pem had the highest probability of being the best treatment option (P-score =0.911), followed by TACE + Anl + Sin (P-score =0.890), TACE + Don + Tor (P-score =0.862), TACE + Len + Tis (P-score =0.822), and TACE + Apa + Cam (P-score =0.763) (Figure 3D).

ORR

For ORR, 22 treatment regimens were included (Figure 4A). Compared with TACE, several triple-combination regimens showed significant ORR benefit, including TACE + Anl + Sin, TACE + Ate + Bev, TACE + Don + Tor, TACE + Len + Cam, TACE + Len + Pem, TACE + Len + Tis, TACE + Sor + Cam, and TACE + Sor + Sin (Figure 4B,4C).

Figure 4 Network meta-analysis of objective response rate. (A) Network plot. Nodes represent different interventions, and the size of each node is proportional to the sample size or number of studies included for the corresponding treatment. Lines indicate direct comparisons between two interventions, and the thickness of each line is proportional to the number of studies for that direct comparison. (B) Forest plot of each treatment relative to TACE. Squares represent effect size estimates, horizontal lines indicate 95% CIs, and the vertical line represents the line of no effect. (C) League table of pairwise comparisons among all treatments. (D) Bar chart of the P-score values for all treatments. A P-score closer to 1 indicates a higher ranking in overall therapeutic efficacy. Anl, anlotinib; Apa, apatinib; Ate, atezolizumab; Bev, bevacizumab; Bri, brivanib; Cam, camrelizumab; CI, confidence interval; Don, donafenib; HR, hazard ratio; Len, lenvatinib; Ora, orantinib; Pem, pembrolizumab; Sin, sintilimab; Sor, sorafenib; Sun, sunitinib; TACE, transarterial chemoembolization; Tis, tislelizumab; Tor, toripalimab.

According to the P-score ranking, TACE + Len + Cam had the highest probability of being the best treatment option (P-score =0.960), followed by TACE + Len + Tis (P-score =0.902), TACE + Don + Tor (P-score =0.824), TACE + Anl + Sin (P-score =0.810), and TACE + Apa + Cam (P-score =0.717) (Figure 4D).

DCR

For DCR, 22 treatment regimens were included (Figure 5A). Compared with TACE, several triple-combination regimens showed significant DCR benefit, including TACE + Anl + Sin, TACE + Apa + Cam, TACE + Ate + Bev, TACE + Don + Tor, TACE + Len + Cam, TACE + Len + Pem, TACE + Len + Tis, TACE + Sor + Cam, and TACE + Sor + Sin (Figure 5B,5C).

Figure 5 Network meta-analysis of disease control rate. (A) Network plot. Nodes represent different interventions, and the size of each node is proportional to the sample size or number of studies included for the corresponding treatment. Lines indicate direct comparisons between two interventions, and the thickness of each line is proportional to the number of studies for that direct comparison. (B) Forest plot of each treatment relative to TACE. Squares represent effect size estimates, horizontal lines indicate 95% CIs, and the vertical line represents the line of no effect. (C) League table of pairwise comparisons among all treatments. (D) Bar chart of the P-score values for all treatments. A P-score closer to 1 indicates a higher ranking in overall therapeutic efficacy. Anl, anlotinib; Apa, apatinib; Ate, atezolizumab; Bev, bevacizumab; Bri, brivanib; Cam, camrelizumab; CI, confidence interval; Don, donafenib; HR, hazard ratio; Len, lenvatinib; Ora, orantinib; Pem, pembrolizumab; Sin, sintilimab; Sor, sorafenib; Sun, sunitinib; TACE, transarterial chemoembolization; Tis, tislelizumab; Tor, toripalimab.

According to the P-score ranking, TACE + Len + Tis had the highest probability of being the best treatment option (P-score =0.960), followed by TACE + Ate + Bev (P-score =0.893), TACE + Anl + Sin (P-score =0.838), TACE + Apa + Cam (P-score =0.825), and TACE + Sor + Sin (P-score =0.693) (Figure 5D).

Publication bias and inconsistency analysis

The publication bias analysis for OS, PFS, ORR, and DCR showed that the Egger’s test results were not statistically significant (OS: P=0.72; PFS: P=0.68; ORR: P=0.90; DCR: P=0.23) (Figure 6). The comparison-adjusted funnel plots for OS, PFS, ORR, and DCR were generally symmetrical, suggesting a low likelihood of publication bias among the included studies (Figure 6).

Figure 6 Funnel plots. (A) Overall survival; (B) progression-free survival; (C) objective response rate; (D) disease control rate.

The results of the global inconsistency test showed no statistically significant differences, indicating that there was no significant global inconsistency in the overall network structure and supporting the use of a consistency model for effect size pooling (Table S6). The node-splitting analysis showed no significant differences between direct and indirect comparisons, and no obvious locally inconsistent loops were identified (Figures S1-S4).

Discussion

In this NMA, we systematically compared the efficacy of TACE combined with different MTAs and/or ICIs for uHCC. The results showed that, compared with TACE alone, most combination regimens achieved varying degrees of benefit in OS, PFS, ORR, and DCR, suggesting that TACE-based combination strategies may be more advantageous than local therapy alone in the treatment of uHCC. Further ranking results indicated that, although the performance of different combination regimens was not entirely consistent across efficacy endpoints, triple therapy combining TACE with MTAs and ICIs generally demonstrated the best efficacy, particularly TACE + Anl + Sin, TACE + Len + Tis, and TACE + Apa + Cam.

As a stand-alone treatment, TACE has long been one of the important standard therapies for uHCC, especially in patients with intermediate-stage disease. However, its limitations are also obvious. Previous studies have shown that the hypoxic microenvironment induced by TACE can markedly upregulate factors such as HIF-1α and VEGF, thereby promoting tumor revascularization, residual lesion growth, and extrahepatic metastasis. This may partly explain why TACE alone is often unable to provide sustained improvement in patient outcomes. Llovet et al. (122), while acknowledging the role of TACE in uHCC, also noted that only selected patients may benefit from it, whereas durable disease control is often not achieved in patients with advanced disease or highly aggressive tumor biology. Similarly, systemic therapy alone also has limitations. Although MTAs can partly compensate for the inability of local therapy to control micrometastases and systemic disease, their tumor response rates remain limited, and rapid reduction of intrahepatic tumor burden is often difficult to achieve. In addition, many patients develop resistance to MTAs within a short period, leading to treatment failure. Therefore, monotherapy usually addresses only one key aspect of tumor progression and cannot simultaneously meet the needs of local control, anti-angiogenesis, and immune remodeling.

Against this background, dual therapy has gradually become a transitional strategy for uHCC. Our study showed that most dual regimens were significantly more effective than TACE alone and sorafenib alone, particularly TACE combined with MTAs. Multiple studies have also confirmed this finding (123,124). However, among specific MTAs, although Sor and Len are both first-line therapies for advanced HCC, their actual efficacy differs when combined with TACE. Our study demonstrated that, except for OS, TACE + Len was significantly superior to TACE + Sor in terms of PFS, ORR, and DCR. This may be related to differences in their target spectra. Sor mainly inhibits VEGFR, PDGFR, and RAF kinase signaling pathways, whereas Len inhibits not only VEGFR1–3 but also FGFR1–4, PDGFRα, RET, and KIT (125). Zhang et al. (126) also reported that TACE + Len achieved better tumor response and survival outcomes than TACE + Sor. These findings are consistent with our analysis.

In addition, our results further suggest that adding ICIs on the basis of dual therapy generally confers superior efficacy. For OS, PFS, ORR, and DCR, the top-ranked regimens were mostly triple therapies combining TACE with MTAs and ICIs. This suggests that triple therapy may represent an important future direction for the comprehensive treatment of uHCC. Mechanistically, these three modalities may act synergistically. First, TACE induces ischemic necrosis of the tumor, releases tumor-associated antigens, and alters the tumor microenvironment, thereby enhancing the antitumor immune response of ICIs (127). In addition, MTAs not only inhibit neovascularization but also normalize tumor vasculature, improving the infiltration of immune cells into the tumor microenvironment (128,129). Among them, TACE + Anl + Sin, TACE + Len + Tis, and TACE + Apa + Cam ranked among the top five across OS, PFS, ORR, and DCR. In addition to the common mechanisms described above, different MTAs and ICIs may exert unique effects. Anl, as a multi-target TKI, can simultaneously inhibit VEGFR, FGFR, PDGFR, and c-Kit, all of which are closely related to angiogenesis and tumor proliferation (130). Moreover, Anl enhances the antitumor efficacy of Sin by inhibiting the VEGFR2-AKT-HIF axis and recruiting PD-1(+)CD8(+) T cells (131). TACE + Len + Tis may benefit from Len’s inhibition of the FGF/FGFR axis, which can reactivate IFN-γ signaling in tumor cells and thereby enhance the antitumor activity of PD-1 blockade (132). In addition, Tis minimizes binding to Fcγ receptors, which may help sustain effector T-cell function (133). As a VEGFR-2-targeted TKI, Apa enhances the efficacy of Cam through the STAT1/NK axis (134).

Importantly, the benefit of triple therapy should not be interpreted as evidence that adding an ICIs to TACE alone is sufficient to achieve comparable efficacy. Rather, the currently available evidence suggests that TACE + ICIs doublets and TACE + MTA/anti-VEGF + ICIs triplets are mechanistically and clinically distinct strategies. A particularly informative example is the three-arm EMERALD-1 trial (100), in which TACE + Dur did not significantly improve PFS compared with TACE alone, whereas TACE + Dur + Bev did achieve a significant PFS benefit. This internal comparison suggests that the anti-angiogenic component may be important for generating effective synergy with immunotherapy in the TACE setting, rather than serving as a merely additive component. Biologically, this interpretation is plausible because anti-angiogenic agents may counteract the post-TACE pro-angiogenic rebound, normalize tumor vasculature, and facilitate immune-cell infiltration, thereby creating a more favorable microenvironment for ICIs. In contrast, the evidence base for TACE + ICIs alone remains limited and less conclusive, consisting mainly of small early-phase or retrospective studies. Therefore, the superior ranking of several triple regimens in our network should be understood as likely reflecting the combined contribution of both the MTA/anti-VEGF backbone and the ICIs component, rather than the effect of immunotherapy alone.

However, the superiority of different triple regimens was not consistent across outcome measures, suggesting that different combinations of MTAs and ICIs may have distinct therapeutic emphases. On the one hand, this may be related to differences in drug targets, anti-angiogenic potency, immunomodulatory capacity, and the timing of combination with TACE. On the other hand, baseline patient characteristics in the included studies, such as tumor burden, Child-Pugh class, and the presence of metastasis, also varied. Therefore, the P-score results should not be interpreted as absolute superiority, but rather as a probabilistic ranking based on the current evidence.

Nevertheless, this study has several limitations. First, most included studies were retrospective cohort studies, and RCTs were lacking, which inevitably introduced selection bias, confounding bias, and information bias, thereby affecting the robustness of the conclusions. Second, some treatment regimens were supported by only a small number of studies and had small sample sizes, which may have limited the precision of the effect estimates. Third, there was substantial clinical heterogeneity in TACE implementation across studies. Important procedural factors, such as TACE type (cTACE vs. DEB-TACE), retreatment strategy (scheduled vs on-demand), and catheter selectivity, were not consistently reported and therefore could not be fully accounted for in the network analysis. Fourth, because some studies did not directly report point estimates and 95% CIs, survival data had to be extracted from Kaplan-Meier curves, which may have introduced measurement error. Moreover, the current OS evidence for major triple-combination regimens is still evolving. While network estimates suggested potential OS benefit for several triple therapies, mature confirmatory data from pivotal phase III trials are limited. This evidence immaturity reduces the certainty of indirect comparisons and may affect the robustness of treatment rankings. Finally, the included studies were mainly from Asia, especially China, where the etiologies of HCC differ from those in Western countries. Therefore, the generalizability of our findings requires further validation.

Conclusions

This NMA indicates that, for patients with uHCC, TACE combined with MTAs and/or ICIs provides more significant benefits in terms of OS, PFS, ORR, and DCR compared with TACE alone. Overall, TACE-based combination strategies are superior to local therapy alone, and triple therapy demonstrates a more pronounced therapeutic advantage. Among the various combination regimens, TACE + Anl + Sin, TACE + Len + Tis, and TACE + Apa + Cam showed favorable efficacy across multiple outcome measures, suggesting that they may represent more promising treatment options for the comprehensive management of uHCC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA-NMA reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0436/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0436/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0436/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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