Current hepatocellular carcinoma (HCC) staging systems lack comprehensive assessment of tumor biologic characteristics. This study aimed to develop and validate a tumor biology characteristics score (TBCS) based on alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) to predict long-term oncologic outcomes after HCC resection.

In this multicenter retrospective cohort study, patients who underwent curative resection for HCC between June 2018 and December 2022 were included. TBCS (range, 2-6 points) was calculated by combining preoperative AFP (<20, 20-199, and ≥200 ng/mL) and PIVKA-II levels (<40, 40-399, and ≥400 mAU/mL). Patients were stratified into low (2 points), medium (3-4 points), and high TBCS groups (5-6 points). The primary outcomes were recurrence-free survival (RFS) and overall survival (OS).

A total of 695 patients were analyzed; the low, medium, and high TBCS groups comprised 132 (19.0%), 233 (33.5%), and 330 patients (47.5%), respectively. Notably, 5-year RFS was 30.4%, 14.7%, and 9.7%, whereas 5-year OS was 42.1%, 35.5%, and 23.5% for low, medium, and high TBCS groups, respectively (both P <.001). Multivariate analysis identified TBCS as an independent predictor of both RFS (medium TBCS: hazard ratio [HR], 1.583; 95% CI, 1.219-2.057; P =.001; high TBCS: HR, 1.895; 95% CI, 1.473-2.438; P <.001) and OS (high TBCS: HR, 1.781; 95% CI, 1.353-2.343; P <.001).

The novel TBCS combining AFP and PIVKA-II effectively stratified patients with HCC into distinct prognostic groups after curative-intent resection, independently predicting both RFS and OS. This score may help identify high-risk patients for more intense postoperative recurrence surveillance and receipt of adjuvant therapies.

The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.

RNA-binding proteins (RBPs) are critical regulators in tumorigenesis and therapy resistance by modulating RNA metabolism. However, the role of RBPs in hepatocarcinogenesis and progression remains elusive. Here, RBPs screening and integrating analyses identify major vault protein (MVP) as an oncogenic RBP in the occurrence of hepatocellular carcinoma (HCC) and sorafenib resistance via suppressing ferroptosis. Mechanistically, reactive oxygen species (ROS) induces STAT3-mediated MVP transcription activation and high expression in HCC cells. Subsequently, phosphoglycerate mutase family member 5 (PGAM5) directly dephosphorylates MVP at S873, facilitating its binding to the mRNA of iron-sequestering cytokine LCN2 and maintains its stability, thereby attenuating ferroptosis by reducing lipid peroxidation and intracellular Fe2+ content following sorafenib treatment. Notably, tenapanor, a potent pharmacological inhibitor of MVP, effectively disrupts the interaction between MVP and LCN2 mRNA and enhances ferroptosis and sorafenib sensitivity. Collectively, these findings underscore the central role of MVP in hepatocarcinogenesis and offer promising avenues to improve HCC treatment.

This study presents a translational modeling framework designed to predict tumor size dynamics in cancer patients undergoing anticancer treatment, using data from patient-derived xenograft (PDX) mice. In the first step, a population tumor growth inhibition (TGI) model to estimate the distribution of exponential tumor growth rates and anticancer drug potency in PDX mice was built. Then, model parameters were allometrically scaled from mice to humans to inform a TGI model predicting tumor size dynamics in cancer patients. Longitudinal tumor dynamics predicted by the PDX-informed TGI model were expressed in terms of tumor progression events to allow validation against literature time-to-progression (TTP) data. The proposed approach was tested on two case studies: gemcitabine treatment for pancreatic cancer and sorafenib treatment for hepatocellular cancer. The framework successfully predicted median tumor size dynamics, closely aligned with clinical TTP curves for gemcitabine-pancreatic cancer case study. While predictions for extreme tumor size percentiles highlighted potential avenues for refinement, such as incorporating resistance mechanisms, the overall accuracy underscored the goodness of the approach. For the sorafenib-hepatocellular cancer case study, the framework provided plausible tumor size predictions, with TTP curves closely aligned with clinical observations, despite the limited availability of clinical data prevented a full validation. Overall, the translational modeling framework showed potential for predicting tumor dynamics in cancer patients, with results suggesting its applicability as a valid tool to support early decision-making in oncology.

Atezolizumab plus bevacizumab (A/B) is a first-line therapy for unresectable hepatocellular carcinoma (HCC). Only a small proportion of patients respond to treatment. This study integrated radiomic and clinical data derived from routine pre-treatment imaging to predict outcomes after immunotherapy.

152 patients from two international centres receiving A/B were retrospectively reviewed. Deep learning autosegmentation generated whole liver masks from pre-treatment CTs. Radiomic features combined with clinical variables were used to predict 12-month mortality post A/B. Radiomic and integrated radiomic-clinical models were developed using 7 machine learning models in combination with 13 feature selection techniques in the Imperial College London (ICL) cohort. K-means clustering identified high- and low-risk groups and predicted overall survival (OS), progression-free survival (PFS) and response. Model performance was assessed in the independent Assistance Publique-Hôpitaux de Paris (AP-HP) cohort.

The integrated radiomic-clinical model outperformed BCLC stage (AUC 0.61, p<0.001) and ALBI grade (AUC 0.48, p<0.001) in ICL (AUC 0.89, 95% CI 0.75-0.99) and AP-HP (AUC 0.75, 95% CI 0.64-0.85) cohorts. Integrated model-stratified high-risk patients had significantly shorter median OS (ICL: 5.6 months vs. 28.2 months; p<0.001; AP-HP: 5.8 months vs. 15.7 months; p<0.001) and PFS (ICL: 2.4 months vs. 14.6 months; p<0.001; AP-HP: 2.1 months vs. 6.1 months; p=0.046). Low-risk patients had significantly higher ICI response rates compared to high-risk patients (35.6% vs. 21.4%; p=0.038). In multivariable analysis, radiomic group was the strongest predictor of OS (HR 3.22, 95% CI 1.99-5.20; p<0.001) and PFS (HR 1.82, 95% CI 1.18-2.80; p=0.010).

Radiomic-based models predict survival outcomes and response to immunotherapy in patients with advanced HCC. Deep learning in combination with machine learning can stratify patients and allows for precision treatment strategies.

There is a lack of prognostic markers predicting survival and response after immunotherapy in hepatocellular carcinoma. This study used deep learning and machine learning to develop and validate an integrated radiomic-clinical model which can predict survival and response to atezolizumab plus bevacizumab from pre-treatment imaging. Radiomic-based machine learning models can risk-stratify advanced HCC patients receiving atezolizumab plus bevacizumab.

Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. With the approval of multiple first- and second-line agents, especially the combination therapies based on immune checkpoint inhibitor (ICI) regimens, the landscape of systemic therapy for advanced HCC (aHCC) is more diverse than ever before. The efficacy of current systemic therapies shows great heterogeneity in patients with aHCC, thereby identifying biomarkers for response prediction and patient stratification has become an urgent need. The main biomarkers for systemic therapy in hepatocellular carcinoma are derived from peripheral blood, tissues, and imaging. Currently, the understanding of the clinical response to systemic therapy indicates unequivocally that a single biomarker cannot be used to identify patients who are likely to benefit from these treatments. In this review, we provide an integrated landscape of the recent development in molecular targeted therapies and ICIs-based therapies, especially focusing on the role of clinically applicable predictive biomarkers. Additionally, we further highlight the latest advancements in biomarker-driven therapies, including targeted treatments, adoptive cell therapies, and bispecific antibodies.

Over the past years, there has been a remarkable advance in the systemic treatment options for advanced HCC. The overall survival has gradually increased over time, with larger benefits for patients with sensitive tumors and preserved liver function, the latter being an essential condition for the delivery of sequential lines of treatment and optimization of clinical outcomes. With the approval of new first-line agents and the introduction of immune checkpoint inhibitor-based therapies, the treatment landscape of advanced HCC is becoming wider than ever. Atezolizumab plus bevacizumab and, more recently, durvalumab plus tremelimumab have entered the clinical practice and are the current standard of care for treatment-naïve patients, surpassing sorafenib and lenvatinib monopoly. As no head-to-head comparisons are available among all the first-line treatment options, the recommendation for the most appropriate choice and sequence is patient-driven and integrates efficacy data with clinical comorbidities, background liver disease, and the safety profile of available drugs. In addition, predictive biomarkers for successful patients' stratification are yet to be available and constitute the focus of ongoing research. The treatment algorithm is likely to become even more complex since systemic therapeutic approaches are now being translated into earlier stages of the disease, with an impact on the evolution of the sequential treatment of patients with HCC.

Systemic treatment for unresectable hepatocellular carcinoma (HCC) has rapidly advanced, with immune checkpoint inhibitors now the preferred first-line option. However, with multiple agents available and no established treatment sequence, selecting the most suitable second-line (2L) therapy remains challenging. While sorafenib is frequently chosen for 2L treatment, comprehensive data supporting its use is limited. This study evaluates the effectiveness of sorafenib as 2L therapy and factors influencing outcomes following first-line treatment failure in advanced HCC patients.

This is a retrospective, multicenter study, including 81 patients with unresectable HCC from 12 European centers who received sorafenib as 2L treatment. Median overall survival (mOS), median progression-free survival (mPFS), radiological response to treatment, and toxicity were evaluated. Univariable and multivariable analyses were performed to identify potential predictors of clinical benefit.

In this cohort, some patients were treated with 2L sorafenib mOS for 7.4 months (95% CI: 6.6-13.6) and other patients were treated with mPFS for 3.7 months (95% CI: 3.0-4.8). Multivariable analysis revealed the best median OS for patients with CP A and AFP levels < 400 ng/mL (15.5 months). Adverse events (AE) of grade ≥ 3 were reported in 59.4% of patients.

In this real-world cohort of European patients with unresectable HCC, the outcome of sorafenib treatment in the 2L setting was comparable to that of the other established 2L treatment options in patients with preserved liver function and good performance status. This study contributes to the understanding of the role of sorafenib in the 2L setting and underscores the need for further research to identify predictive factors for response and survival in order to optimize treatment algorithms for advanced HCC.

The combination of nivolumab and ipilimumab has demonstrated significant antitumor activity in first-line treatment for hepatocellular carcinoma (HCC) and in second-line treatment following progression on sorafenib. However, the efficacy and safety of ipilimumab plus anti-PD-1/PD-L1 antibodies combination therapy in advanced HCC patients who have progressed after multiple lines of treatment have not yet been reported.

We conducted a multicenter retrospective study that included 33 HCC patients who had progressed after multiple lines of immune-targeted therapy and received ipilimumab combination therapy. All patients had received at least one line of immunotherapy based combination therapy (excluding those treated with anti-CTLA-4 inhibitors). The primary endpoints were overall survival (OS) and progression-free survival (PFS). Efficacy was assessed using RECIST 1.1, while adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0).

Among the patients, 29 (87.9%) received ipilimumab combination therapy as third-line or later line therapy. The median OS for the entire cohort was 14.07 months (95% CI: 5.57 months - not evaluable), and the median PFS was 2.36 months (95% CI: 1.97-5.64 months). Univariate survival analysis indicated that an NLR ≥ 3.1 and tumor size ≥ 63 mm are prognostic risk factors for OS (P=0.03 and P=0.027, respectively). Multivariate survival analysis revealed that an NLR ≥ 3.1 is the only independent prognostic risk factor for OS (P=0.048). The overall response rate (ORR) was 12.1%, and the disease control rate (DCR) was 48.5%. One patient experienced treatment-related death (3%), two had hyperprogression (6.1%), and three discontinued treatment due to adverse events (9.1%).

Ipilimumab combination therapy in very late lines is a viable treatment option, although careful monitoring for adverse events is essential. Earlier application of this combination may potentially benefit patients more effectively.

Alpha-fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver-related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea. Patients with a baseline serum AFP test and no HCC diagnosis on imaging within 3 months were included. Patients were categorised into high-AFP (≥ 10 ng/mL) and normal-AFP (< 10 ng/mL) groups. The primary outcome was the incidence of HCC within 2 years, with secondary outcomes focused on longitudinal changes in AFP and liver-related laboratory values. Propensity score matching (PSM) and Cox proportional hazard models were used to assess HCC risk. After 1:4 PSM, 1278 high-AFP and 3731 normal-AFP patients were analysed. The high-AFP group had a significantly higher 2-year incidence of HCC (HR: 4.29; 95% CI: 3.31-5.57). AFP levels increased in patients who developed HCC in both groups (p < 0.01). Among the high-AFP group, patients who did not develop HCC had elevated baseline alanine aminotransferase levels (p < 0.01), which decreased during follow-up (p < 0.01) unlike those who developed HCC. In conclusion, baseline AFP elevation in CHB patients is associated with an increased risk of developing HCC within 2 years. Longitudinal monitoring of AFP and liver-related laboratory values can help in risk stratification.

Liver cancer, primarily HCC, exhibits highly heterogeneous histological and molecular aberrations across tumors and within individual tumor nodules. Such intertumor and intratumor heterogeneities may lead to diversity in the natural history of disease progression and various clinical disparities across the patients. Recently developed multimodality, single-cell, and spatial omics profiling technologies have enabled interrogation of the intertumor/intratumor heterogeneity in the cancer cells and the tumor immune microenvironment. These features may influence the natural history and efficacy of emerging therapies targeting novel molecular and immune pathways, some of which had been deemed undruggable. Thus, comprehensive characterization of the heterogeneities at various levels may facilitate the discovery of biomarkers that enable personalized and rational treatment decisions, and optimize treatment efficacy while minimizing the risk of adverse effects. Such companion biomarkers will also refine HCC treatment algorithms across disease stages for cost-effective patient management by optimizing the allocation of limited medical resources. Despite this promise, the complexity of the intertumor/intratumor heterogeneity and ever-expanding inventory of therapeutic agents and regimens have made clinical evaluation and translation of biomarkers increasingly challenging. To address this issue, novel clinical trial designs have been proposed and incorporated into recent studies. In this review, we discuss the latest findings in the molecular and immune landscape of HCC for their potential and utility as biomarkers, the framework of evaluation and clinical application of predictive/prognostic biomarkers, and ongoing biomarker-guided therapeutic clinical trials. These new developments may revolutionize patient care and substantially impact the still dismal HCC mortality.

Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) are recommended to receive systemic therapy according to guidelines. Stereotactic body radiotherapy (SBRT) and surgery are increasingly used in this patient population. This study compares outcomes from these local treatments.

Patients diagnosed with HCC with MVI and treated with surgery or SBRT between 1999 and 2022 were included. Propensity score matching minimized bias from confounders. Overall survival (OS) was analyzed using the Kaplan-Meier method,. and local, regional, and distant recurrences were assessed via competing risk methods. Univariable and multivariable analyses adjusted by the Lasso method evaluated OS predictors.

Among 175 patients, 38 underwent surgery and 137 received SBRT. The median age was 61 years, tumor volume was 158.6 cc, and α-fetoprotein level was 197 IU/mL. Most surgical patients had major resection (74%) via an open approach (97%). The median biologically effective dose (BED) for SBRT was 53.7 Gy. After matching, 35 patients per group had a median OS of 16 months. Local failure was higher in the SBRT group (20%) than in the surgery group (12%) at 1 year (p = 0.028). Distant failure was more frequent in surgery (54%) compared with SBRT (17%) [p = 0.003]. Excluding SBRT patients receiving adjuvant systemic therapy did not change the results. In-hospital mortality was 9% post-surgery and 14% experienced post-SBRT liver impairment.

Both surgery and SBRT offer good long-term OS and control. Surgery provides better local control, while SBRT had lower distant relapse. While SBRT has acceptable toxicity, surgery carries a significant mortality risk.

PD-L1 and VEGF blockade with atezolizumab plus bevacizumab has been shown to improve survival in unresectable hepatocellular carcinoma. TIGIT is an immune checkpoint regulator implicated in many cancers, including unresectable hepatocellular carcinoma. Here, we evaluate the clinical activity and safety of the addition of tiragolumab, an anti-TIGIT monoclonal antibody, to atezolizumab plus bevacizumab.

This randomised, open-label, phase 1b-2 umbrella study was conducted at 26 centres across China, France, Israel, New Zealand, South Korea, Taiwan, and the USA. Eligible patients were adults aged 18 years old or older with previously untreated locally advanced unresectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0-1, Child-Pugh class A disease, and a life expectancy of at least 3 months. Eligible patients were randomly assigned (2:1) using permuted block randomisation to receive either tiragolumab 600 mg plus atezolizumab 1200 mg plus bevacizumab 15 mg/kg or atezolizumab 1200 mg plus bevacizumab 15 mg/kg, administered via intravenous infusion every 3 weeks on day 1 of each 21-day cycle. Patients received treatment until unacceptable toxic effects or loss of clinical benefit, whichever occurred first. The primary endpoint was objective response rate. Analysis of clinical activity was done in the efficacy-evaluable population (all patients who received at least one dose of each drug for their assigned treatment regimen) and safety was assessed in all patients who received any study treatment. The trial is registered with ClinicalTrials.gov, NCT04524871, and is ongoing.

Between Aug 20, 2020, and Feb 10, 2022, we assessed 154 patients for eligibility and 59 eligible patients were randomly assigned to receive tiragolumab plus atezolizumab plus bevacizumab (n=41) or atezolizumab plus bevacizumab (n=18); one patient in the tiragolumab plus atezolizumab plus bevacizumab group experienced an adverse event before receiving any treatment and withdrew from the study. Median age was 65·0 years (IQR 61·0-73·0). 46 (79%) of 58 patients were male and 12 (21%) were female. Most patients were Asian (23 [40%]) or White (21 [36%]). At the time of clinical cutoff (Aug 21, 2023), median follow-up was 20·6 months (IQR 10·6-28·0) in the tiragolumab plus atezolizumab plus bevacizumab group and 14·0 months (4·2-18·5) in the atezolizumab plus bevacizumab group. The confirmed objective response rate was 43% (95% CI 27-59, n=17) in the tiragolumab plus atezolizumab plus bevacizumab group and 11% (1-35, n=2) in the atezolizumab plus bevacizumab group. All patients in both groups experienced an adverse event. The incidence of pruritis (20 [50%] of 40 patients vs three [17%] of 18 patients), arthralgia (13 [33%] vs two [11%]), and diarrhoea (12 [30%] vs one [6%]) was notably higher in the tiragolumab plus atezolizumab plus bevacizumab group than in the atezolizumab plus bevacizumab group, although these were mainly grade 1-2. The most common grade 3-4 adverse events were hypertension (six [15%] of 40 patients in the tiragolumab plus atezolizumab plus bevacizumab group vs two [11%] of 18 patients in the atezolizumab plus bevacizumab group), aspartate aminotransferase increased (three [8%] of 40 patients vs one [6%] of 18 patients), and proteinuria (two [5%] of 40 patients vs two [11%] of 18 patients). Serious adverse events occurred in 21 (53%) of 40 patients in the tiragolumab plus atezolizumab plus bevacizumab group and in ten (56%) of 18 patients in the atezolizumab plus bevacizumab group. Treatment-related deaths occurred in one patient in the tiragolumab plus atezolizumab plus bevacizumab group (due to cholestasis) and two patients in the atezolizumab plus bevacizumab group (due to oesophageal varices haemorrhage and upper gastrointestinal haemorrhage). The addition of tiragolumab to atezolizumab plus bevacizumab did not appear to result in a substantial worsening of treatment-related or immune-mediated adverse events, and no new safety signals were identified.

This signal-seeking study suggests that the addition of tiragolumab to atezolizumab and bevacizumab might be more clinically active than atezolizumab plus bevacizumab alone in unresectable hepatocellular carcinoma. Based on these data, further study of combination tiragolumab plus atezolizumab plus bevacizumab is warranted.

F Hoffmann-La Roche and Genentech.

Cirrhotic patients with super-giant hepatocellular carcinoma (HCC) and portal vein invasion generally have a poor prognosis. This paper presents a patient with super-giant HCC and portal vein invasion, who underwent hepatectomy followed by a combination of sorafenib and camrelizumab, resulting in complete remission (CR) for 5 years.

A 40-year-old male with compensated hepatitis B-related cirrhosis was diagnosed with HCC, Barcelona Clinic Liver Cancer stage C. Enhanced computed tomography imaging revealed a 152 mm × 171 mm tumor in the right liver, invading the portal vein and hepatic vein. Liver function was normal. The patient successfully underwent hepatectomy on July 18, 2019. However, by December 2019, HCC recurrence with lung metastases and portal vein invasion were detected. He started treatment with sorafenib (200 mg twice daily) and camrelizumab (200 mg every 3 weeks). By May 12, 2020, the patient was confirmed to have CR. Camrelizumab was adjusted to 200 mg every 12 weeks from June 16, 2021, with the last infusion on March 29, 2024. Although no further tumor recurrence was observed, he experienced two episodes of gastrointestinal bleeding due to esophagogastric varices, which were managed with endoscopic therapy. To date, the patient has remained in CR for 5 years.

The combination of hepatectomy with sorafenib and camrelizumab can achieve durable CR in patients with super-giant HCC and portal vein invasion. Further research is necessary to address these challenges and improve patient outcomes.

Predicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy.

We analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023. A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. The SII cutoff value, determined using X-tile analysis based on overall survival (OS) in the training cohort, divided patients into high (> 752*109) and low (≤ 752*109) SII groups. Prognostic factors were identified through univariate and multivariate logistic and Cox regression analyses, and survival outcomes were assessed using Kaplan-Meier methods. The predictive accuracy of SII was evaluated using receiver operating characteristic (ROC) curves.

An optimal SII cutoff of 752*109 stratified patients into high and low SII groups. Univariate and multivariate logistic regression indicated that SII was a significant predictor of the objective response rate (ORR), which was markedly different between the low and high SII subgroups (34.72% vs. 9.52%, P = 0.019). This finding was consistent in the validation cohort (34.09% vs. 16.28%, P = 0.026). SII also demonstrated prognostic value in Cox regression and Kaplan-Meier analyses. ROC curves confirmed that SII had superior predictive accuracy compared to common clinical indicators, with predictive relevance even in AFP-negative patients. Furthermore, a lower SII was associated with a higher T cell ratio and an increased number of CD8+ T cells and Granzyme B+ CD8+ T cells in peripheral blood.

SII is a promising predictor of both therapeutic efficacy and prognosis in HCC patients undergoing immune-based treatments. Its application may enhance clinical decision-making, thereby improving patient outcomes from immune-based therapy.

Sora is the first-line drug for advanced hepatocellular carcinoma (HCC). However, acquired resistance to Sora treatment largely hinders its therapeutic efficacy, and the mechanisms underlying Sora resistance remain poorly understood. Here, we revealed a new mechanism by which Sora promotes the differentiation of regulatory T (Treg) cells to suppress the immune response in the HCC tumor microenvironment (TME) and induce Sora resistance.

Human liver tissues were obtained from HCC patients. Female C57BL/6J, OT-II, and Foxp3GFP mice were also used. Flow cytometry was used to analyze immune cells in TME. Flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay were performed to evaluate Treg cell differentiation. Immunoblotting was conducted to identify relevant proteins. Mouse and human tumor tissues were evaluated via multiplex immunofluorescence staining. Sora-treated HCC tissues and Sora-treated Treg cells were subjected to RNA sequencing analysis. Tumor models were generated and treated with Sora, Sora combined with an anti-CD25 antibody, or Sora combined with the Foxo1 inhibitor AS1842856.

First, we found through bioinformatic analysis that Sora suppresses the immune response in HCC. Furthermore, Sora increased the Treg cell population to promote the formation of an immunosuppressive TME in HCC. In vitro, Sora promoted Treg cell differentiation and increased the immunosuppressive activity of Treg cells. Activating VEGF and AKT abolished the effect of Sora on Treg cell differentiation, whereas inhibiting Foxo1 compromised Sora-induced Treg cell differentiation, indicating that the induction of Treg cells by Sora is dependent on the VEGFR/AKT/Foxo1 pathway. Finally, Treg inactivation by an anti-CD25 antibody or the Foxo1 inhibitor AS1842856 in combination with Sora showed greater efficacy in the treatment of HCC.

Sora induced Treg cell differentiation by inhibiting VEGFR/AKT signaling and activating Foxo1, thus suppressing the immune response and reducing Sora efficacy. Treg inactivation might be a promising strategy to alleviate the immunosuppressive TME and overcome Sora resistance.

Although the number of studies on sorafenib for hepatocellular carcinoma (HCC) is increasing during the past two decades, no detailed scientometric examination of its knowledge framework has been undertaken. Therefore, we performed a bibliometric analysis on this topic.

VOSviewer and CiteSpace were utilized to analyze the articles regarding sorafenib for HCC from 2005 to 2024, which were retrieved from the Web of Science Core Collection (WoSCC) database.

There were 7,667 articles related to sorafenib in HCC were retrieved from the WoSCC database, and they covered 99 countries/regions, 5,640 institutions, and 30,450 authors. The most published literature of countries and institutions were China and Sun Yat-sen University, respectively. Cancers is the journal with the most papers published in this field, and the journal with the most co-citations is N Engl J Med. Among authors, Masatoshi Kudo has published the most research papers, and the most co-citations go to JM Llovet. The keywords "survival", "apoptosis", "efficacy", "transarterial chemoembolization", "lenvatinib", etc. represent the current hotspots in this field.

We identified current hotspots and trends by bibliometric analysis in sorafenib-HCC field, which might provide valuable guidance for future researches. Further explorations are supposed to conduct the continued study of HCC apoptosis, large-scaled clinical trials with international cooperations, and comprehensive treatments including multiple systemic or locoregional approaches in patients with HCC.

Hepatocellular carcinoma (HCC) remains a major challenge in oncology, being a leading cause of cancer-related mortality worldwide. Early-stage HCC is typically treated with surgical resection, transplantation, or ablation, while advanced-stage HCC relies on systemic therapies like sorafenib and newer combinations such as atezolizumab-bevacizumab. Despite these advancements, there is still a need for effective treatments for unresectable HCC, especially in cases with macroscopic vascular invasion. Hepatic arterial infusion chemotherapy (HAIC) has demonstrated promising outcomes in Asia for the treatment of unresectable HCC, yet its application in Western countries has been relatively limited. This letter reviews the recent meta-analysis by Zhou et al published in the World Journal of Gastrointestinal Oncology, which demonstrates the efficacy and safety of HAIC vs sorafenib. The analysis includes 9 randomized controlled trials and 35 cohort studies, highlighting significant improvements in overall survival, progression-free survival, and objective response rates with HAIC and its combinations. The editorial explores the reasons behind the limited use of HAIC in Western countries. It underscores the potential of HAIC to enhance treatment outcomes for advanced HCC and calls for more research and broader adoption of HAIC in clinical practice globally.

In recent years, with the decline in HBV and HCV infections, there has been a corresponding reduction in both the morbidity and mortality of virus-associated HCC. Nevertheless, rising living standards, coupled with the increasing prevalence of metabolic disorders like diabetes and obesity, have led to a rapid surge in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) incidence. The mechanisms underlying the progression from NAFLD to NAFLD-HCC are multifaceted and remain incompletely understood. Current research suggests that genetic predisposition, metabolic dysregulation, lipotoxicity, oxidative stress, and inflammation are key contributing factors. Given the complexity of these mechanisms and the frequent occurrence of metabolic comorbidities like type 2 diabetes mellitus (T2DM) and cardiovascular disease in NAFLD-HCC patients, there is a pressing need for tailored therapeutic strategies, along with novel prevention, monitoring, and treatment approaches that are personalized to the patient's pathophysiology. Due to the limited depth of research, incomplete understanding of pathogenesis, and insufficient clinical data on NAFLD-HCC treatment, current therapeutic approaches largely rely on tumor staging. In this review, we synthesize current research on the pathogenesis, surveillance, diagnosis, treatment, and prevention of NAFLD-HCC, and offer perspectives for future studies, particularly regarding its underlying mechanisms.

This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases.

In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023.

Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non-conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non-conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non-conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively).

Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible.

There is still poor evidence about the safety and feasibility of laparoscopic liver resection (LLR) for huge (> 10 cm) hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long-term outcomes of LLR versus open liver resection (OLR) for patients with huge HCC from real-life data from consecutive patients.

Data regarding all consecutive patients undergoing liver resection for huge HCC were retrospectively collected from a Korean referral HPB center. Primary outcomes were the postoperative results, while secondary outcomes were the oncologic survivals.

Sixty-three patients were included in the study: 46 undergoing OLR and 17 LLR. Regarding postoperative outcomes, there were no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications, and R1 resection rates. After a median follow-up of 48.4 (95% CI 8.9-86.8) months, there were no statistically significant differences in 3 years OS (59.3 ± 8.7 months vs. 85.2 ± 9.8 months) and 5 years OS (31.1 ± 9 months vs. 73.1 ± 14.1 months), after OLR and LLR, respectively (p = 0.10). Similarly, there was not a statistically significant difference in both 3 years DFS (23.5% ± 8.1 months vs. 51.6 ± months) and 5 years DFS (15.7 ± 7.1 months vs. 38.7 ± 15.3 months), respectively (p = 0.13), despite a potential clinically significant difference.

LLR for huge HCC may be safe and effective in selected cases. Further studies with larger sample size and more appropriate design are needed to confirm these results.

This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC).

The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.

12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001).

Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.

Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment.

The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT).

Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function.

Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis.

PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Hepatocellular carcinoma (HCC) is the sixth most prevalent form of cancer globally and the third leading cause of cancer-related mortality. The incidence of portal vein tumor thrombosis (PVTT) in HCC patients is 21% at one year and 46% at three years. The presence of PVTT has consistently been associated with a poor prognosis for HCC patients over the past decades. Notably, HCC prognosis is influenced not only by the presence of PVTT but also by the degree or extent of PVTT. Currently, there is a lack of global consensus or established protocols regarding the optimal management of HCC with associated PVTT. The Barcelona Clinic for Liver Cancer classifies HCC patients with PVTT as stage C, indicating an advanced stage, and limiting treatment recommendations for these patients to systemic therapy. In recent years, there has been an increase in the availability of therapeutic options for HCC patients with PVTT. Treatment modalities include systemic therapy, transarterial chemoembolization, surgical resection, stereotactic body radiotherapy, transarterial radioembolization, and liver transplantation. An ideal therapy for each patient necessitates a multidisciplinary approach. This review article presents the latest updates in managing HCC patients with PVTT.

Primary liver cancer is a major health problem being the sixth most frequent cancer in the world and the third cause of cancer-related death in the world. The most common histological type of liver cancer is hepatocellular carcinoma (HCC, 75-80%).

Based on primary literature, this review provides an updated analysis of studies of genetic characterization of HCC at the level of gene mutation profiling, copy number alterations, and gene expression, with the definition of molecular subgroups and the identification of some molecular biomarkers and therapeutic targets. Recent therapeutic developments are also highlighted.

Deepening the understanding of the molecular complexity of HCC is progressively paving the way for the development of more personalized treatment approaches. Two important strategies involve the definition and validation of molecularly defined therapeutic targets in a subset of HCC patients and the identification of suitable biomarkers for approved systematic therapies (multikinase inhibitors and immunotherapies). The extensive molecular characterization of patients at the genomic and transcriptomic levels and the inclusion of detailed and relevant translational studies in clinical trials will represent a fundamental tool for improving the benefit of systemic therapies in HCC.

Circular RNAs (circRNAs) lack the 5'-end methylated guanine cap structure and 3' polyadenylate tail structure, classifying it as a non-coding RNA. With the extensive investigation of circRNA, its role in regulating cell death has garnered significant attention in recent years, establishing it as a recognized participant in cancer's biological processes. Autophagy, an essential pathway in programmed cell death (PCD), involves the formation of autophagosomes using lysosomes to degrade cellular contents under the regulation of various autophagy-related (ATG) genes. Numerous studies have demonstrated that circRNA can modulate the biological activity of cancer cells by influencing the autophagy pathway, exhibiting a dualistic role in suppressing or promoting carcinogenesis. In this review, we comprehensively analyze how autophagy-related circRNA impacts the progression of gastrointestinal cancer (GIC). Additionally, we discuss drug resistance phenomena associated with autophagy regulation in GIC. This review offers valuable insights into exploring potential biological targets for prognosis and treatment strategies related to GIC.

A high baseline NLR is associated with a poor prognosis of immunotherapy in patients with advanced HCC. As anti-tumour immune activation takes time, early dynamic changes in NLR may serve as a biomarker for predicting immunotherapy response. We conducted a retrospective study in which we enrolled 209 patients with aHCC who received ICIs (training cohort: N = 121, validation cohort: N = 88). In the training cohort, we categorized the patients based on the early changes in their NLR. Specifically, we defined patients as NLR Stable-Responder, NLR Responder and NLR Non-Responder. We compared the outcomes of these three patient groups using survival analysis. Additionally, we shortened the observation period to 6 weeks and validated the findings in the validation cohort. In the training cohort, early dynamic changes in NLR (HR 0.14, 95%CI 0.03-0.65, p = 0.012, HR 0.19, 95%CI 0.07-0.54, p = 0.002; HR 0.21, 95%CI 0.10-0.42, p < 0.001, HR 0.40, 95%CI 0.23-0.69, p = 0.001), PD-L1 < 1% (HR 5.36, 95%CI 1.12-25.66, p = 0.036; HR 2.98, 95%CI 1.51-5.91, p = 0.002) and MVI (HR 3.52, 95%CI 1.28-9.69, p = 0.015; HR 1.99, 95%CI 1.14-3.47, p = 0.015) were identified as independent predictors of OS and PFS. In the validation cohort, when the observation period was reduced to 6 weeks, early NLR changes still have predictive value. Early dynamic changes in NLR may be an easily defined, cost-effective, non-invasive biomarker to predict aHCC response to ICIs.

The triple combination of programmed cell death protein-1 (PD-1) inhibitors plus anti-angiogenesis tyrosine kinase inhibitors (TKIs) with or without transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) enhance the effect of treatment for unresectable hepatocellular carcinoma (uHCC). The present study compared the efficacy and safety of PD-1 plus TKI with or without transarterial chemo(embolization) for uHCC.

The meta-analysis was conducted using data acquired from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials.gov from the inception date to December 2023. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were used to measure the pooled effect. In addition, subgroup analysis was conducted to determine the specific patient population that benefited.

The OS (HR = 0.47; 95% CI: 0.39-0.56, P <  0.05), PFS (HR = 0.52; 95% CI: 0.45-0.60, P < 0.05), and ORR (RR = 1.94; 95% CI: 1.60-2.35, P < 0.05) were significantly better in TACE/HAIC+TKI+PD-1(TACE/HAIC TP) group than TKI+PD-1(TP) group. The incidence of AEs was acceptable.

The triple therapy of TACE/HAIC TP had better efficacy for uHCC than TP, with acceptable security.

PROSPERO, identifier CRD42023475953.

This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.

Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.

Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.

Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.

This study aimed to assess the effectiveness and safety of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib (LEN) and PD-1 inhibitors in treating arterioportal shunt (APS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT).

Conducted retrospectively, the study enrolled 54 HCC patients with APS and PVTT treated with HAIC, LEN, and PD-1 inhibitors at our center between January 2021 and October 2023. APS improvement, APS recanalization, tumor response, PVTT response rate, overall survival (OS), intrahepatic progression-free survival (InPFS), and adverse events were evaluated.

APS improvement was observed in 42 patients (77.8%), with all improvement occurring within two treatment sessions. Complete APS occlusion was achieved in 40 patients (74.1%), and no recanalization occurred. The best objective response rate (ORR) and ORR after two HAIC sessions were 74.1% and 66.7%, respectively. The best PVTT response and PVTT response after two HAIC sessions were 98.1% and 94.4%, respectively. The median OS and InPFS were 10.0 months and 5.0 months, respectively. OS and InPFS were longer in patients with APS occlusion compared to those without (OS 12.1 vs 4.4 months, P<0.001, InPFS 6.2 vs 2.3 months, P=0.049). ALBI grade, extrahepatic spread, APS disappearance were potential prognostic factors for OS, while APS grade and extrahepatic spread being independently associated with InPFS. No treatment-related mortality occurred.

Combining HAIC with LEN and PD-1 inhibitors proves to be both effective and safe in managing APS in HCC with PVTT, potentially improving patient survival.