Macrophage dysfunction serves as a pivotal factor in the delayed healing of diabetic wounds. Fibroblast growth factor 21 (FGF21) inhibits inflammation and promotes tissue regeneration, but it's limited by short half-life and poor stability. Poloxamer (P) hydrogel is a sustained drug delivery system. Therefore, this study aimed to investigate the role of macrophage dysfunction on the promotion of wound healing by rhFGF21-P hydrogel in type 2 diabetes mellitus (T2DM) murine models and murine peritoneal macrophages (MPMs) stimulated with high glucose and LPS (HG + LPS) for in vitro studies. P hydrogel sustained the release and enhanced the stability of rhFGF21. RhFGF21-P administration accelerated diabetic wound closure and reduced the levels of TNF-α, IL-6, MCP-1 and MIP-2 in diabetic mouse serum and skin tissues as well as in HG + LPS-stimulated MPMs. RhFGF21-P attenuated the fluorescence intensity of F4/80 and increased the level of autophagy in T2DM wound mice. RhFGF21 enhanced phagocytic capacity and the expression of LC3II protein in HG + LPS-stimulated MPMs, and the regulation of rhFGF21 in inflammatory cytokines and phagocytosis was reversed by autophagy inhibitors (3MA and CQ). In addition, rhFGF21 downregulated the levels of STING in vivo and in vitro. Furthermore, rhFGF21 increased the expression of LC3II protein, inhibited the mRNA levels of inflammatory cytokines (TNF-α and IL-6) and enhanced phagocytosis in HG + LPS-treated MPMs, but these effects were reversed by the STING agonist Vadimezan. These results demonstrated that rhFGF21-P promoted diabetic wound healing through inhibiting the expression of inflammatory cytokines and enhancing phagocytic function of macrophages via the modulation of STING-mediated autophagy.

4121 Background: Conversion therapy allows a subset of patients with initially unresectable hepatocellular carcinoma (uHCC) to achieve a deep pathological response, enabling curative resection. However, the optimal duration of postoperative adjuvant therapy remains unclear. This prospective randomized study compared recurrence-free survival (RFS) and overall survival (OS) between 3-month and 6-month durations of postoperative adjuvant therapy after R0 resection in patients achieving major pathological response (MPR; ≥90% tumor necrosis) or pathological complete response (pCR). Methods: This randomized controlled trial (ChiCTR2100051789) enrolled patients with uHCC who achieved a MPR or pCR following conversion therapy. Eligibility criteria included pathological confirmation of MPR or pCR after R0 resection. Eligible patients were randomized 1:1 to receive 3 months (Group 3M) or 6 months (Group 6M) of postoperative adjuvant therapy starting 1 month after surgery. The primary endpoint was RFS; secondary endpoints included OS and recurrence patterns. Results: Between January 15, 2022, and April 20, 2025, 58 patients were randomized (29 per group). Pathological evaluation confirmed MPR in 21 patients and pCR in 37 patients. After a median follow-up of 33.05 months, recurrence occurred in 8 patients. The 1-, 2-, and 3-year RFS rates were 89.3%, 89.3%, and 78.8% in Group 3M and 88.9%, 88.9%, and 88.9% in Group 6M (P = 0.592). Corresponding OS rates were 100%, 96.4%, and 96.4% versus 100%, 91.8%, and 91.8%, respectively (P = 0.451). Conclusions: In patients with uHCC who achieved a deep pathological response (MPR or pCR) after conversion therapy, a shorter duration of adjuvant therapy may be sufficient, with a 3-month course providing survival outcomes comparable to those of a 6-month course. Clinical trial information: ChiCTR2100051789.

Background & Aims:The combination of transarterial chemoembolization (TACE), lenvatinib and PD-1 inhibitors (triple therapy) demonstrates encouraging efficacy in patients with unresectable hepatocellular carcinoma (uHCC). But its prognostic value remains unclear in patients with double negative des gamma carboxy prothrombin (DCP) and alpha fetoprotein (AFP) uHCC. To identify the best candidates for this treatment, this study aimed to evaluate the prognosis of this specific population and to establish a practical prognostic scoring model. Methods:This multicenter retrospective study included 136 patients with double-negative DCP/AFP uHCC receiving triple therapy, stratified into training (n=91) and validation (n=45) cohorts. Independent predictors for overall survival (OS) were identified by Cox regression to build a scoring system. The model's performance was validated using Kaplan-Meier curves and the area under the receiver operating characteristic curve (AUC). Results:In the training cohort, median OS was not reached, and median progression-free survival was 18.9 months. Additionally, triple therapy produced a 79.1% objective response rate and a 95.6% disease control rate. Four variables (maximal tumor size ≥ 5 cm, absence of conversion surgery, presence of extrahepatic metastasis, and age < 55 years), were independent risk factors for prognosis and were utilized to develop the SEA score. The SEA score effectively stratified patients into low risk (0-3 points) and high risk (4-6 points) groups, with significantly different survival outcomes in both cohorts. This model showed robust discriminative performance, with AUCs of 0.80 in the training cohort and 0.68 in the validation cohort, and outperformed all individual prognostic factors. Conclusion:Triple therapy demonstrates promising efficacy and an acceptable safety profile in patients with double-negative DCP/AFP uHCC. The SEA score effectively stratifies patient outcomes, facilitating the identification of optimal candidates for triple therapy, though prospective validation is warranted before widespread clinical use.

Background:The triple therapy regimen of transcatheter arterial chemoembolization (TACE) plus lenvatinib and PD-1 inhibitors plays a significant role in the treatment of unresectable hepatocellular carcinoma (uHCC). However, only a subset of patients can benefit from it, making it crucial to screen for those who may benefit from the triple therapy regimen. This study constructed and assessed a survival prediction nomogram for uHCC patients undergoing first-line triple therapy. Methods:Using retrospective data from 277 consecutive triple-therapy patients (treated at six Chinese centers between 2018-2023), we constructed the nomogram based on multivariate-derived predictors. Model performance was quantified through discrimination metrics and bootstrapped internal validation. External validation employed an independent cohort (n=208) from three additional institutions. Results:Independent predictors of overall survival (OS) included alpha-fetoprotein (AFP), maximum tumor diameter, tumor number, extrahepatic metastasis, and platelet-to-lymphocyte ratio (PLR). A PLANES model was constructed to predict 12-, 24-, and 36-month OS. The model demonstrated robust discriminative performance, with area under the curve (AUC) values of 0.887, 0.793 and 0.749 for 12-, 24-, and 36-month OS in the training cohort, respectively. External validation yielded AUCs of 0.922, 0.760, and 0.722 for corresponding time points. Conclusions:The PLANES model was successfully established and validated for predict prognosis in unresectable HCC patients receiving first-line triple therapy.

Brain aging is characterized by memory loss and cognitive impairment. With the growth of the population and advances in medical care, the size of the aging population is increasing. Therefore, the discovery of anti-aging drugs has become a popular topic in recent years. Fibroblast growth factor 21 (FGF21) has been reported to inhibit oxidative stress, reduce inflammation, and delay senescence. The present study was designed to investigate the effects of recombinant human FGF21 (rhFGF21) on senescence in the brain in a mouse model of D-galactose (D-gal)-induced aging. The behavioral tests revealed that rhFGF21 improved D-gal-induced learning and memory impairment in mice. RhFGF21 improved the morphology of cortical and hippocampal neurons and increased the expression of PSD95 in the model mice. RhFGF21 reduced the number of microglia and astrocytes in the cortex and hippocampus, increased the activities of the antioxidant enzymes (GSH-PX, CAT, and SOD), and inhibited the expression of p-NFκB and p53 proteins, as well as the mRNA expression of the inflammatory cytokines (IL-1β, IL-6, TNFα, and iNOS). SIRT1 regulates senescence and inflammation, and FGF21 participates in physiological and pathological processes by binding to the FGFR1. Therefore, we measured SIRT1 and activated FGFR1 (p-FGFR1) levels. RhFGF21 administration increased the expression of cortical and hippocampal SIRT1 and p-FGFR1 in D-gal-induced aging mice. These data suggested that rhFGF21 alleviated learning and memory impairment in a mouse model of D-gal-induced aging by increasing antioxidant enzyme activity, inhibiting inflammation, and senescence-related gene expression via modulating FGFR1 and SIRT1.

Diabetic foot ulcers are among the most common complications of diabetes and can lead to delayed wound healing. Fibroblast growth factor (FGF1) is a classic drug for the treatment of skin wounds but has the disadvantages of a short half-life and instability. Poly (lactic-co-glycolic acid) (PLGA) nanofibers are sustained-release biomaterials that have potential for use as therapeutic delivery systems. However, the therapeutic effect of PLGA loaded with recombinant human FGF1 (rhFGF1) on diabetic wound healing is unknown. Therefore, this study aimed to explore the therapeutic effects of PLGA-rhFGF1 in type 2 diabetic (T2D) wound mice. We found that PLGA offers good sustained release, which enhances the stability and bioactivity of rhFGF1. PLGA-rhFGF1 promoted wound closure, re-epithelialization and the expression of keratin 10 and keratin 14 in T2D mice on day 14. PLGA-rhFGF1 significantly decreased the levels of TNF-α and IL-6 in serum and skin tissues as well as the level of IL-1β in skin tissues. Moreover, PLGA-rhFGF1 decreased the mRNA levels of CXCL1, MCP1 and MIP2, and the fluorescence intensity of F4/80 and Ly6G in T2D wound mice and increased the collagen content and the protein expression of collagen I in the dermis of T2D wounds. PLGA-rhFGF1 also increased blood flow; the mRNA levels of the angiogenesis-related factors VEGF, Ang-1 and eNOS and the fluorescence intensity of CD31 in T2D wound mice. These data indicate that PLGA releases rhFGF1 slowly and promotes skin wound healing in T2D mice. The mechanisms through which PLGA-rhFGF1 produces these effects involve decreased inflammation and the promotion of granulation, re-epithelialization and angiogenesis.

BACKGROUND:Triple therapy of transcatheter arterial chemoembolization (TACE) combined with lenvatinib and anti-PD-1 antibodies has demonstrated excellent efficacy in unresectable hepatocellular carcinoma (uHCC). However, tumor drug resistance is still a major problem and the rate of complete response in uHCC following triple therapy is relatively low. This study aimed to investigate the efficacy and safety of sequential radiotherapy after triple therapy in patients with uHCC to improve tumor response rate. METHODS:This retrospective study included 29 patients with uHCC who received sequential radiotherapy after achieving partial response (PR) or stable disease (SD) in tumor response per the modified Response Evaluation Criteria in Solid Tumors (mRECIST) after triple therapy. The overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were analyzed to evaluate the efficacy of this regimen. Treatment-related adverse events were assessed to determine the safety profile. RESULTS:Among the 29 patients, the median OS had not yet been reached, and the median PFS was 19.43 months. The 24-month OS and PFS rates were 72.8% and 46.5%, respectively. The lesions of 6 patients initially with tumor response of PR achieved complete response, and the lesions of 12 patients with SD achieved PR after sequential radiotherapy. All adverse events were manageable, and no treatment-related death occurred. CONCLUSION:Sequential radiotherapy after triple therapy enhanced tumor response and survival benefits for uHCC patients, with manageable adverse effects.

Introduction:Management of patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh class B liver function is challenging owing to compromised hepatic functional reserve, affecting treatment selection and outcomes, as many systemic therapies demonstrate altered pharmacokinetics and increased toxicity in this population. Current treatment guidelines predominantly focus on patients with preserved liver function (Child-Pugh A), creating a critical evidence gap for the optimal management of patients with Child-Pugh B liver function. This network meta-analysis (NMA) evaluated first-line therapies for patients with advanced HCC and Child-Pugh B cirrhosis, addressing current evidence gaps to guide optimal treatment selection for this high-risk population. Methods:The PubMed, Embase, and Cochrane Library databases were searched until 31 October 2024. Randomized controlled trials and prospective cohort studies were included if they involved patients with advanced HCC and Child-Pugh class B liver function, evaluated first-line therapeutic agents, and reported overall survival (OS) and/or progression-free survival (PFS) with 95% confidence intervals. Bayesian NMA was employed to evaluate treatment efficacy and safety. Results:Eleven studies comprising 2,536 patients were included in the NMA. Lenvatinib exhibited the greatest probability of ideal efficacy for OS, while atezolizumab and bevacizumab combination therapy demonstrated the highest likelihood of optimal performance in terms of PFS. The overall incidence of adverse events (AEs) was 68.58%. The predominant grade 3-4 AEs included hypertension, proteinuria, hand-foot syndrome, and abnormal liver function. Conclusion:Atezolizumab and bevacizumab combination therapy demonstrated the optimal net benefit regarding PFS and reduced toxicity, whereas lenvatinib monotherapy exhibited the greatest net benefit in OS but with increased toxicity.

Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) is a promising therapy for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the characteristics and identify predictors of long-term survival (LTS) in advanced uHCC treated with triple therapy. Retrospectively reviewed patients with uHCC who underwent triple therapy between June 2018 and May 2023 at 8 hospitals in China. LTS was defined as an overall survival (OS) ≥ 24 months. Kaplan-Meier curves were used to estimate survival. Univariate and multivariate logistic regression analyses were performed to identify predictors of LTS. A total of 110 patients were included in this study. With a median follow-up of 31.3 months, the median OS and progression-free survival for the entire cohort were 17.9 months (95% confidence interval [CI], 13.8-21.2) and 11.8 months (95% CI, 9.9-15.3), respectively. Thirty-nine (35.5%) patients had LTS, with 36- and 48-month OS rates of 95.8% and 82.1%, respectively. In contrast, the median OS for patients with non-LTS was 10.9 months (95% CI, 9.9-13.2). The independent predictors of LTS were the absence of portal vein tumor thrombus (odds ratio [OR], 13.71; 95% CI, 3.19-88.08; p < .001), absence of extrahepatic metastasis (OR, 7.81; 95% CI, 2.76-25.82; p < .001), and platelet-albumin-bilirubin grade 1 (OR, 3.15; 95% CI, 1.17-9.15; p = .023). The absence of portal vein tumor thrombus, absence of extrahepatic metastasis, and platelet-albumin-bilirubin grade 1 were significantly associated with LTS. These findings help guide treatment decisions in advanced uHCC.

Background: Ultraviolet B (UVB) irradiation can damage skin tissue. Diabetes aggravates skin lesions. Fibroblast growth factor 21 (FGF21) is significantly involved in exerting protective effects and facilitating tissue repair. Therefore, this study aimed to investigate the impact of recombinant human FGF21 (rhFGF21) on diabetic skin affected by UVB damage.Methods: UVB irradiation (270 mJ/cm2) was administered to diabetic mice for 5 consecutive days to establish UVB-irradiated skin injury, and rhFGF21 was administered daily after irradiation. Human immortalized keratinocytes (HaCaT) and mouse peritoneal macrophages (MPMs) were cultured under high glucose (HG) conditions for 3 days, followed by treatment with rhFGF21 for 1 h before UVB irradiation or lipopolysaccharide (LPS) stimulation. We analyzed the effects of UVB irradiation on diabetic skin via laser Doppler flowmetry, histopathological staining, TUNEL assays, RT-PCR, Western blotting, MTT assays and Hoechst 33258 staining.Results: Our findings indicated that the skin of diabetic mice was more severely damaged by UVB irradiation, and rhFGF21 alleviated this damage. RhFGF21 inhibited apoptosis and inflammatory responses in the skin tissues of diabetic mice. These changes were primarily reflected in increase of the sirtuin 1 (SIRT1) level in epidermal cells and peritoneal macrophages of mice. Moreover, rhFGF21 not only increased the survival rate of HaCaT cells but also decreased the generation of pro-inflammatory cytokines in MPMs. Notably, SIRT1 inhibitor (EX527) was capable of reversing these effects.Conclusions: RhFGF21 attenuates UVB-induced damage to the skin of diabetic mice, predominantly by suppressing epidermal cell apoptosis and macrophage-mediated inflammatory responses via the SIRT signaling pathway.

Combination therapy plays a critical role in optimizing surgical outcomes for patients with locally advanced hepatocellular carcinoma (HCC) complicated by bile duct tumor thrombus (BDTT). Current neoadjuvant strategies integrate local and systemic modalities to reduce tumor burden and recurrence rate. However, the combination of transarterial chemoembolization (TACE), lenvatinib, and PD-1 inhibitors (triple therapy) as a neoadjuvant regimen for HCC with BDTT has not been previously reported. Here, we present the case of a 61-year-old man with HBV-associated HCC and BDTT, initially deemed high-risk for direct resection due to tumor size (7 cm) and biliary involvement. The patient underwent one session of TACE followed by two months of lenvatinib (12 mg/day) and sintilimab (200 mg every 3 weeks). Post-treatment contrast-enhanced MRI revealed complete resolution of BDTT and partial response of the primary tumor. Subsequent right hemihepatectomy confirmed extensive tumor necrosis (>90%) with negative margins. At 15-month follow-up, surveillance imaging showed no recurrence. The patient experienced only grade 1 hypertension, managed without treatment interruption. This case highlights the potential of triple therapy as a neoadjuvant approach to downstage advanced HCC with BDTT, enabling curative resection while maintaining a manageable safety profile. Further studies are warranted to validate its efficacy in larger cohorts and define optimal treatment protocols.

INTRODUCTION:Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS:In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS:The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION:The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

Background:This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery. Methods:This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts. Results:No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229-1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119-1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092-0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079-0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373-4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147-372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent. Conclusion:At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.

PURPOSE:The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. MATERIALS AND METHODS:This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. RESULTS:During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. CONCLUSION:Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.

Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti-PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC.

Purpose: The prognosis of hepatocellular carcinoma (HCC) with extrahepatic metastases (EM) is poor. The efficacy and safety of transcatheter arterial chemoembolization combined with lenvatinib plus anti-programmed cell death 1 inhibitors (triple therapy) for HCC with EM remains unclear. In this study, we aimed to determine the efficacy and safety of triple therapy in HCC patients with EM. Patients and Methods: This study retrospectively reviewed HCC patients with EM who received triple therapy and analyzed their survival rate using the Kaplan-Meier method. Univariate prognostic analysis of each data point was performed using the Log rank test, and multivariate prognostic analysis was performed using the Cox proportional risk regression model. Results: Among 60 HCC patients with EM who underwent triple therapy, the most common sites of metastasis were as follows (in descending order): the lungs (n=27), lymph nodes (n=22), and bones (n=10). After triple therapy, the median progression-free survival and median overall survival were 6 and 18.63 months, respectively. The 6-month, 1-year, and 2-year cumulative survival rates were 87.7%, 68.6%, and 26.8%, respectively. In the multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) >= 4 and alpha-fetoprotein (AFP) level >= 400 ng/mL were independently associated with overall survival. Conclusion: Our findings revealed that triple therapy is an effective, well-tolerated regimen for HCC patients with EM. AFP level and NLR are prognostic risk factors for triple therapy in this patient population.