Most adjuvant therapies for hepatocellular carcinoma (HCC) have failed except for autologous cytokine-induced killer (CIK) therapy, which prolonged recurrence-free survival (RFS) in a previously reported randomized controlled trial (RCT) and real-world data (RWD). This study aimed to assess the long-term outcomes of adjuvant CIK therapy using both an extended follow-up of the original RCT and a retrospective cohort study. An extended follow-up analysis of the RCT included 226 patients (114 in the CIK group and 112 in the control group). The follow-up duration was extended from 2 to 9 years after the enrollment of the last patient. In parallel, a retrospective RWD study was performed involving 577 patients from two tertiary centers in Korea, including 251 who received adjuvant CIK therapy and 326 controls. Propensity score matching (PSM) was applied to adjust for baseline imbalances. The primary endpoint was RFS in both studies. In the RWD study (median follow-up = 57.2 months), the CIK group demonstrated significantly prolonged RFS than controls both before PSM (median = 101.2 versus 64.7 months; HR = 0.69, 95

Background Gut microbiota play an integral role in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to clarify the potential ameliorative effects of Multi-biotics (a freeze-dried product containing prebiotics, probiotics, and postbiotics) on diet-induced MASLD. Methods Forty-eight C57BL/6 mice were evenly divided into three groups according to diet type: standard diet (SD); choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD); and CDAHFD supplemented with Multi-biotics (CDAHFD+Multi-biotics). The blood, feces, and liver tissues were collected at weeks 8 (early stage MASLD, n = 24) and 30 (late-stage MASLD, n = 24). Results Mice in the two CDAHFD groups developed steatohepatitis at weeks 8 and 30, unlike those in the SD group. The NAFLD activity score showed that the addition of Multi-biotics was significantly associated with reduced steatosis at weeks 8 and 30. Gut microbiota, including the Muribaculaceae and Ruminococcaceae families, were significantly decreased in the CDAHFD group, compared with those in the SD and CDAHFD+Multi-biotics groups at week 8. Transcriptomic analysis indicated that mice in the CDAHFD+Multi-biotics group showed upregulated macrophage-targeting anti-inflammatory signals, such as Nr4a1 , whereas the pro-inflammatory TLR4 signal was downregulated. These transcriptomic findings were corroborated by qPCR and Western blot analysis, which showed consistent trends at the mRNA and protein levels, respectively. Conclusions Multi-biotics may modulate gut microbiota and support improvements in hepatic inflammation and steatosis. The integration of multi-omics data provides valuable mechanistic insight into the therapeutic potential of Multi-biotics.

PURPOSE:Immunotherapy has significantly improved outcomes in advanced hepatocellular carcinoma (HCC). However, most patients eventually progress, and second-line (2L) options remain limited. Fostroxacitabine bralpamide (fostrox), a liver-targeted prodrug, was administered in combination with lenvatinib, aiming at enhancing antitumor activity while avoiding further deterioration of residual liver function. PATIENTS AND METHODS:This multicenter, single-arm phase Ib/IIa study evaluated the safety, pharmacokinetics (PK)/pharmacodynamics, and efficacy of fostrox (orally for 5 days in 21-day cycles), plus lenvatinib (standard doses), in locally advanced unresectable or metastatic HCC progressed on first-line/2L therapy (NCT03781934). A 3 + 3 dose-escalation design was used to determine the recommended phase II dose (RP2D). RESULTS:Twenty-one patients were enrolled, and the median follow-up was 10.5 months. No dose-limiting toxicities were observed, and the RP2D of fostrox was established at 30 mg. All patients reported adverse events (AE), with 81% being grade ≥3 with possible relation to fostrox in 52.5% and to lenvatinib in 66.7% of cases. Fostrox-related AEs were mainly transient neutropenia and thrombocytopenia. Other AEs, mainly attributed to lenvatinib, were grade I/II and consistent with monotherapy use. Fostrox dose reduction and discontinuation rates were 29% and 5%, and for lenvatinib the rates were 52% and 14%, respectively. There were no signs of treatment-related liver function deterioration. The overall response rate was 24%, disease control rate was 81%, median time to progression was 10.9 months, median progression-free survival was 6.7 months, and median overall survival was 13.7 months. Fostrox PK analyses confirmed dose proportionality, and liver biopsies showed tumor-selective DNA damage. CONCLUSIONS:The combination of fostrox and lenvatinib demonstrated promising preliminary efficacy and tolerability after immunotherapy, supporting further investigation as a 2L option in advanced HCC.

BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent among young adults and may contribute to cancer development. However, the impact of longitudinal changes in MASLD status on cancer risk remains unclear. This study aimed to evaluate the association between changes in MASLD status and subsequent cancer incidence in young adults. METHODS:Adults aged 20-39 years who underwent two consecutive health screening examinations-one between 2009-2012 and another between 2011-2014-were identified from the Korean National Health Insurance Service database. Participants were classified into four groups based on changes in MASLD status: non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for the development of cancer. RESULTS:During a median follow-up of 10.6 years, 95,666 (2.7 %) of 3536,172 participants developed cancer. Compared with the non-MASLD group, the persistent MASLD group exhibited the highest overall cancer risk (HR = 1.15; 95 % CI = 1.13-1.18), followed by the incident MASLD group (HR = 1.03; 95 % CI = 1.00-1.06). The resolved MASLD group showed no significant difference in cancer risk (HR = 1.02; 95 % CI = 0.98-1.05). Persistent MASLD was further associated with elevated risks of laryngeal, biliary, renal, hepatic, pancreatic, and colorectal cancers. Among women, persistent MASLD was linked to higher risks of uterine corpus, cervical, and ovarian cancers. CONCLUSIONS:Incident and persistent MASLD in young adults are associated with increased overall and site-specific cancer risks, whereas individuals whose MASLD improved showed no significant excess risk. Early identification and management of MASLD may help reduce future cancer burden.

BACKGROUNDS/AIMS:Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE. METHODS:Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP. RESULTS:The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively. CONCLUSIONS:Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as the first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Emerging evidence suggests that immune-related adverse events (irAEs) may be associated with improved ICI efficacy. This study evaluated the impact of adverse events during atezolizumab plus bevacizumab therapy on clinical outcomes in patients with unresectable HCC. Methods: This retrospective study included consecutive patients receiving first-line atezolizumab plus bevacizumab for unresectable HCC. IrAEs and bevacizumab-related adverse events were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5.0). Imaging studies conducted during treatment were reviewed to identify asymptomatic, imaging-detected adverse events. Overall survival (OS) was the primary endpoint and was analyzed using time-dependent Cox regression. The secondary endpoint was the disease control rate (DCR). Results: Among the 198 enrolled patients, 12 had imaging-detected irAEs without symptoms (asymptomatic AE group), whereas 56 experienced clinical symptoms of irAEs (n = 28), bevacizumab-related adverse events (n = 19) or both (n = 9) (symptomatic AE group). The OS rates at 6, 12, 18, and 24 months were 100.0%, 82.5%, 82.5%, and 82.5%, respectively, in the asymptomatic AE group; 89.1%, 64.1%, 41.7%, and 40.5%, respectively, in the symptomatic AE group; and 72.3%, 48.3%, 31.3%, and 19.4%, respectively, for the non-AE group. Compared with the non-AE group, both the asymptomatic and symptomatic AE groups showed significantly improved OS in the inverse probability of treatment weighting-adjusted time-dependent Cox regression analysis (p = 0.02). The DCR was significantly greater in the asymptomatic AE group (100.0%) and the symptomatic AE group (91.8%) than in the non-AE group (60.0%) (p < 0.001). Conclusion: Adverse events during atezolizumab plus bevacizumab therapy are associated with improved OS and treatment response in unresectable HCC patients. Asymptomatic imaging-detected irAEs may serve as prognostic factors, highlighting the value of proactive imaging in patient management.

This study compared denosumab and bisphosphonates for osteoporosis in tenofovir-exposed chronic hepatitis B patients. Both denosumab and bisphosphonates increased bone mineral density (BMD) at year 1. However, denosumab resulted in a greater BMD improvement and a more pronounced reduction in procollagen type 1 N-terminal peptide (P1NP) compared to bisphosphonate. These findings suggest that while both drugs have beneficial effects, denosumab may be the more effective therapeutic option in this population. Tenofovir disoproxil fumarate (TDF), a first-line antiviral for chronic hepatitis B (CHB), is a risk factor for osteoporosis. This study aimed to compare the effectiveness of denosumab and bisphosphonates for osteoporosis in TDF-exposed CHB patients. CHB patients who were treated with either denosumab or bisphosphonates for newly diagnosed osteoporosis during > 1 year of TDF treatment between 2010 and June 2024 were included from two tertiary centers in Korea. The primary outcome was bone mineral density (BMD) change at year 1 in the lumbar spine (LS) and femoral neck (FN). Secondary outcomes included changes in two bone turnover markers, procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type 1 collagen (CTX). A total of 155 patients were included: 79 received denosumab and 76 received bisphosphonates. The median time from TDF initiation to osteoporosis diagnosis was 4.8 years. After balancing baseline characteristics using propensity score matching, the denosumab group showed a significant increase in BMD at the LS and FN (denosumab vs. bisphosphonates: LS, 11.7

575 Background: EMERALD-1 (NCT03778957) met its primary endpoint, showing improved progression-free survival (PFS) in pts with locoregional HCC treated with D + B + TACE versus PBO + TACE (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.98). This analysis assessed the impact of TACE modality (conventional TACE [cTACE] or drug-eluting bead [DEB]-TACE) on efficacy and safety outcomes. Methods: Pts in this analysis received D (1500 mg) or PBO for D (Q4W) plus cTACE or DEB-TACE (investigator choice; TACE modality was a stratification factor). After completing the last TACE, pts received D (1120 mg) + B (15 mg/kg) or PBO for D + B (Q3W). PFS, time to progression (TTP), and overall response rate (ORR; BICR per RECIST v1.1) with D + B + TACE and PBO + TACE (intent-to-treat population) are reported by TACE modality. Safety was assessed in the safety analysis set (pts received ≥1 dose of study treatment [tx], regardless of randomization). Results: Overall, 59.3% of pts received cTACE and 40.7% received DEB-TACE in the D + B + TACE arm; similarly, 58.5% of pts received cTACE and 41.5% received DEB-TACE in the PBO + TACE arm. Most pts received 1 or 2 TACE procedures in both cTACE (60% in D + B + TACE arm; 67.2% in PBO + TACE arm) and DEB-TACE groups (55.6% in D + B + TACE arm; 53.6% in PBO + TACE arm). Baseline characteristics in the cTACE and DEB-TACE groups were similar, with some differences in the relative distribution of BCLC, HAP, and tumor burden (BCLC Score A; 29.0% vs 17.9%: HAP Score A; 36.5% vs 25.0%: tumor burden within up-to-7 criteria; 56.4% vs 37.5%, respectively). Baseline characteristics were generally well balanced across tx arms within the cTACE and DEB-TACE groups. PFS, TTP, and ORR improved with D + B + TACE versus PBO + TACE, regardless of TACE modality (Table). In the D + B + TACE and PBO + TACE arms, max Grade 3–4 adverse events possibly related to study tx were reported by 25/100 (25.0%) and 3/116 (2.6%) pts in the cTACE group, and 16/54 (29.6%) and 9/84 (10.7%) pts in the DEB-TACE group, respectively. Conclusions: Overall, pts receiving D + B + TACE had improved PFS, TTP, and ORR versus PBO + TACE regardless of TACE modality. Safety was manageable with both cTACE and DEB-TACE. Clinical trial information: NCT03778957 . D + B and cTACE (n=121) PBO and cTACE (n=120) D + B and DEB-TACE (n=83) PBO and DEB-TACE (n=85) Median (95% CI) PFS, months 19.4 (12.4–22.3) 11.1 (7.2–14.0) 11.1 (7.2–14.2) 6.7 (5.0–7.3) PFS HR (95% CI) 0.80 (0.59–1.10) 0.74 (0.51–1.06) Median (95% CI) TTP, months 22.3 (19.4–27.7) 13.6 (9.2–16.6) 15.0 (11.1–22.4) 6.9 (5.1–11.1) TTP HR (95% CI) 0.70 (0.49–0.98) 0.55 (0.36–0.83) Pts with measurable disease at baseline, n 119 119 83 84 ORR, n (%) pts with response* 62 (52.1) 43 (36.1) 26 (31.3) 17 (20.2) ORR, odds ratio (95% CI) 1.93 (1.15–3.27) 1.80 (0.89–3.69) *Includes confirmed complete or partial response.

518 Background: Notwithstanding the pressing need for adjuvant therapy for hepatocellular carcinoma (HCC), most adjuvant therapies, including atezolizumab/bevacizumab, have failed. Meanwhile, adjuvant immunotherapy utilizing autologous cytokine-induced killer (CIK) cells for HCC improved recurrence-free survival (RFS) in a previously reported randomized controlled trial (RCT) and real-world data. This study aimed to assess the longer-term outcomes of the RCT and elucidate the underlying mechanisms of sustained effects of CIK cell treatment. Methods: This study comprised two parts: a long-term follow-up of the preceding RCT and an analysis of immune cells in patients who received adjuvant CIK cell treatment. In the original RCT, 226 patients who underwent curative treatment for stage I or II HCC were randomly allocated to either the CIK (n=114, 16 injections of 6.4×10 9 CIK cells over an 11-month period) or control group (n=112). The follow-up period was extended to 9 years after the enrollment of the last patient. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included cancer-specific survival (CSS) and overall survival (OS). Parallelly, a prospective study was conducted to investigate post-treatment changes of immune cells in peripheral blood of 7 patients, who received repeated transfer of CIK cells after curative treatment for HCC, using flow cytometry. Results: In the extended follow-up of the RCT (median follow-up=115.7 months, interquartile range=74.2–130.5 months), the CIK group sustained a significantly prolonged RFS (median=43.5 vs 27.4 months; hazard ratio [HR]=0.74, 95% confidence interval [CI]=0.55–0.99, P =0.045) and CSS (median=unreached; HR=0.49, 95% CI=0.25–0.95, P=0.04) compared to the control group. Adjuvant CIK cell therapy reduced the risk of overall death by 30%, although it did not achieve statistical significance (median=unreached; HR=0.70, 95% CI=0.44–1.11, P=0.1). A preliminary analysis of peripheral blood immune cells revealed that the CIK cell treatment tended to increase the frequencies of CD8 + and CD4 + classical memory cells. Conclusions: Adjuvant CIK cell treatment demonstrated significantly enhanced RFS and CSS in the prolonged follow-up of the RCT extending to 9 years in patients who received curative treatment for HCC. The CIK group also demonstrated a consistent trend of improved OS. The increase in memory T cell populations might be linked to the sustained off-treatment anti-tumor efficacy of CIK cell treatment.

Although a robust association between metabolic dysfunction-associated fatty liver disease (MASLD) and cardiovascular disease (CVD) has been established, the impact of MASLD on CVD risk in young adults has not been fully evaluated. This population-based study included adults aged 20-39 years who underwent health screening examinations from 2009 to 2012 based on Korean National Health Insurance Service database. MASLD was defined as a fatty liver index >= 30 without any other cause of steatosis, and presence of one or more cardiometabolic risk factors. The primary outcome was newly developed CVD, including myocardial infarction, ischemic stroke, and congestive heart failure. During the median 10.6 years of follow-up, MASLD was observed in 1,435,659 (25.3%) of the 5,666,728 participants. Cumulative incidence of major adverse cardiovascular events was significantly higher in individuals with MASLD compared those without steatosis (P < 0.001). The adjusted hazard ratio (HR) for myocardial infarction was 1.23 [95% CI (confidence interval): 1.18-1.27] in individuals with MASLD compared to those without steatosis. The HR for ischemic stroke and congestive heart failure were higher in individuals with MASLD compared to those without steatosis (HR, 1.12; 95% CI, 1.07-1.17 and HR, 1.18; 95% CI, 1.15-1.21, respectively]. In the subgroup analysis, the elevated HR for CVD in the MASLD group was prominent among individuals who were female and obese. MASLD was associated with an increased risk of CVD in young adults. These findings highlight the need for early intervention in patients with MASLD before they reach middle to reduce the risk of CVD, particularly among young adults in South Korea.

Background/Aims:Current guidelines recommend biannual ultrasound for hepatocellular carcinoma (HCC) surveillance in chronic hepatitis B (CHB) patients. However, computed tomography (CT) or magnetic resonance imaging (MRI) may be used when ultrasound is inadequate. The clinical impact of these alternative modalities remains unclear. Methods:CHB patients undergoing regular HCC surveillance were classified into two groups: ultrasound-only and alternative surveillance (CT/MRI). Patients were stratified into high- and low-risk groups using the Risk Estimation for HCC in CHB (REACH-B) score. Outcomes included 10-year overall survival (OS), HCC tumor size, Barcelona Clinic Liver Cancer (BCLC) stage at diagnosis, and OS after HCC diagnosis. Propensity score matching was applied to balance baseline characteristics. Results:A total of 2,024 patients were included after propensity score matching to ensure balanced baseline characteristics, with 1,012 patients in each group. OS was similar (ultrasound-only 96.0% vs alternative 96.8%; p=0.379). HCC occurred in 66 patients in each group. Alternative surveillance detected smaller HCC tumors (1.6 cm vs 2.1 cm; p<0.001) and more BCLC stage 0 cases (alternative 71.2% vs ultrasound-only 42.4%; p=0.003). The OS after HCC diagnosis was higher with alternative surveillance (83.0% vs 67.0%; p=0.025). In high-risk patients (n=970), alternative surveillance increased the OS (97.3% vs 93.6%; p=0.029) and the OS after HCC diagnosis (83.0% vs 60.6%; p=0.010). No significant differences were observed in low-risk patients. Conclusions:CT/MRI-based alternative surveillance led to earlier HCC detection and improved post-diagnosis survival, particularly in high-risk CHB patients, supporting its potential role as an alternative to ultrasound in selected populations.

Introduction: Biannual ultrasound (US) is recommended for HCC surveillance, although its sensitivity for early-stage HCC is low. This study aims to compare the performance of annual dynamic abbreviated MRI (D-AMRI) and biannual US for HCC detection. Methods: This prospective, two-center cohort study enrolled participants eligible for HCC surveillance according to Korean guidelines between November 2018 and December 2021. Participants underwent four rounds of surveillance at 6-month intervals: both D-AMRI and US at the first and third rounds and only US at the second and fourth rounds. The diagnostic yield (DY) and false referral rate (FRR) were compared between the two modalities. The scan time of D-AMRI was measured using a stopwatch. Results: Of the 257 enrolled participants, 213 participants completed the protocol and were included in the analysis. Primary liver cancers were found in 32 participants, including 31 HCCs (22 very early-stage, eight early-stage, and one advanced-stage) and one intrahepatic cholangiocarcinoma. The DY of annual D-AMRI was higher than biannual US for all (6.4% [26/405] vs. 2.2% [9/405]), early-stage (6.2% [25/405] vs. 2.0% [8/405]), and very early-stage HCCs (4.7% [19/405] vs. 1.2% [5/405]) (p < 0.001 for all). No significant difference in the FRR was observed for all (2.5% [10/405] for both), early-stage (2.7% [11/405] for both) (p > 0.999 for both), and very early-stage HCCs (4.2% [17/405] vs. 3.5% [14/405], p = 0.564). The median scan time of D-AMRI was 13 min. Conclusion: Annual D-AMRI showed a higher DY than biannual US for detecting HCCs, without increasing the FRR.

Supplementary Figure S3. Kaplan–Meier estimates of time to progression and overall survival according to BCLC stage in the per-protocol population. (A) Time to progression. (B) Overall survival. (C) Progression-free survival.

Background Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival. Methods In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries. Eligible patients were randomly assigned (1:1:1), stratified by TACE method, region, and portal vein invasion, using an interactive voice response or web response system, to TACE plus either durvalumab plus bevacizumab (1500 mg intravenous durvalumab once every 4 weeks, then 1120 mg durvalumab plus 15 mg/kg intravenous bevacizumab once every 3 weeks), durvalumab plus placebo (same regimen using placebo instead of bevacizumab), or placebo alone (same regimen using placebo instead of durvalumab and instead of bevacizumab). Participants, investigators, and those assessing outcomes were masked to treatment assignment until data analysis. The primary endpoint was progression-free survival, by blinded independent central review (BICR), and per RECIST version 1.1, with durvalumab plus bevacizumab versus placebo alone in the intention-to-treat population (ITT; ie, all participants assigned to treatment). Key secondary endpoints were progression-free survival by BICR per RECIST version 1.1 with durvalumab plus placebo versus placebo alone, overall survival, and time to deterioration in select patient-reported outcomes. Participants continue to be followed up for overall survival, and overall survival and patient-reported outcomes will be reported in a later publication. Safety was assessed in the safety analysis set, which included all participants assigned to treatment who received any study treatment (ie, any durvalumab, bevacizumab, or placebo) by treatment received. This study is registered with ClinicalTrials.gov, NCT03778957, and is closed to accrual. Findings Between Nov 30, 2018, and July 19, 2021, 887 patients were screened, of whom 616 were randomly assigned to durvalumab plus bevacizumab (n=204), durvalumab plus placebo (n=207), or placebo alone (n=205; ITT population). Median age was 650 years (IQR 590-720), 135 (22%) of 616 participants were female, 481 (78%) were male, 375 (61%) were Asian, 176 (29%) were White, 22 (4%) were American Indian or Alaska Native, nine (1%) were Black or African American, one (<1%) was native Hawaiian or other Pacific Islander, and 33 (5%) were other races. As of data cutoff (Sept 11, 2023) median follow-up for progression-free survival was 279 months (95% CI 274-304), median progression-free survival was 150 months (95% CI 111-189) with durvalumab plus bevacizumab, 100 months (90-127) with durvalumab, and 82 months (69-111) with placebo. Progression-free survival hazard ratio was 077 (95% CI 061-098; two-sided p=0032) for durvalumab plus bevacizumab versus placebo, and 094 (075-119; two-sided p=064) for durvalumab plus placebo versus placebo. The most common maximum grade 3-4 adverse events were hypertension in participants who received durvalumab and bevacizumab (nine [6%] of 154 participants), anaemia in participants who received durvalumab and placebo (ten [4%] of 232 participants), and post-embolisation syndrome in participants who received placebo alone (eight [4%] of 200 participants). Study treatment-related adverse events that led to death occurred in none of 154 participants who received durvalumab and bevacizumab, three (1%) of 232 who received durvalumab and placebo (n=1 for arterial haemorrhage, liver injury, and multiple organ dysfunction syndrome), and three (2%) of 200 who received placebo alone (n=1 for oesophageal varices haemorrhage, upper gastrointestinal haemorrhage, and dermatomyositis). Interpretation Durvalumab plus bevacizumab plus TACE has the potential to set a new standard of care. With additional follow-up of the EMERALD-1 study, future analyses, including the final overall survival data and patient-reported outcomes, will help to further characterise the potential clinical benefits of durvalumab plus bevacizumab plus TACE in hepatocellular carcinoma amenable to embolisation.