Search Results (63)

Leptin (LEP) is an adipocyte-derived cytokine that integrates nutritional status, metabolism, and reproduction in cattle, with particular relevance for modern high-producing dairy cows. In ruminants, LEP and its receptors are widely expressed in metabolic and reproductive tissues, including adipose tissue, liver, hypothalamus, pituitary, ovary, uterus, and placenta, where LEP modulates energy homeostasis, neuroendocrine function, and local tissue responses. Changes in circulating LEP concentrations during the transition period reflect changes in body fat reserve, insulin and GH-IGF-1 dynamics, thyroid hormones, and inflammation and contribute to coordinated metabolic adaptations supporting the onset of lactation. At the reproductive level, LEP influences the hypothalamic–pituitary–gonadal axis, affects the pulsatility of luteinizing hormone (LH) under nutritional stress, and exerts direct effects on ovarian steroidogenesis, folliculogenesis, oocyte competence, embryo development, and uterine immune function. New evidence also links LEP profiles to major peripartum disorders, including subclinical ketosis, insulin resistance, postpartum ovarian inactivity, and uterine inflammatory diseases, and emphasises its potential as part of a panel evaluating the risk of metabolic and reproductive disorders. Furthermore, polymorphisms within the bovine LEP gene and its signalling network have been associated with milk production, feed efficiency, body condition, and fertility traits, suggesting opportunities to incorporate markers into genomic selection schemes aimed at improving robustness and reproductive performance. This review summarises current knowledge on LEP biology in cattle, with an emphasis on dairy cows, and discusses perspectives on translating this information into practical tools for nutritional management, health monitoring, and genetic improvement in bovine production systems. Full article

Background and Objectives: Post-hepatectomy liver failure (PHLF) remains the leading cause of mortality following hepatic resection, with reported incidence rates ranging from 1.2% to 32%. Traditional scoring systems such as the Child–Pugh score, Model for End-Stage Liver Disease (MELD), and Albumin–Bilirubin (ALBI) grade have demonstrated limited predictive accuracy for PHLF. Machine learning (ML) algorithms have emerged as promising tools capable of integrating complex, multidimensional clinical data to improve predictive performance. This systematic review aims to evaluate the current evidence on ML-based prediction models for PHLF, assessing their predictive accuracy, methodological quality, clinical applicability, and the key variables utilized across models. Methods: A systematic literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library from inception to January 2026. Studies that developed or validated ML models for predicting PHLF after hepatic resection were included. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to evaluate the risk of bias. Data on model performance, algorithms employed, sample sizes, predictor variables, and validation strategies were extracted. The review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO. Results: Twelve PubMed-verified studies involving 6913 patients were retained in the final analysis. Publication years ranged from 2020 to 2025, with five studies published in 2025. Gradient boosting approaches (LightGBM/XGBoost or phase-specific boosting models) were the most frequent best-performing architectures, while ANN/deep learning, radiomics-integrated, and ensemble approaches also showed clinically relevant discrimination. Best reported non-training AUCs ranged from 0.7927 to 0.981 (median, 0.873). The strongest generalization signals came from studies with temporal, external, or prospective validation structures. Common predictor domains included bilirubin-based liver function measures, coagulation variables, platelet count, volumetry or extent of resection, imaging-derived radiomics features, and perioperative dynamic data. Conclusions: Machine learning models remain promising for PHLF prediction, but the evidence base is smaller and more heterogeneous than the original draft suggested. Performance is highest in studies that combine clinical liver-reserve markers with imaging or perioperative temporal data; however, widespread clinical adoption is still limited by retrospective design predominance, inconsistent outcome definitions, and incomplete external validation. Full article

Background: Major liver resections that include the removal of four or more Couinaud segments require precise assessment of the future liver remnant (FLR) to prevent post-hepatectomy liver failure (PHLF). Volumetry, although standard in surgical planning, does not always reflect true functional reserve, especially in steatotic, fibrotic or chemotherapy-damaged liver. Methods: This review proposes an integrative physiological framework of functional liver recovery after a major hepatectomy that connects preoperative functional assessments—indocyanine clearance (ICG-PDR), Liver Maximum Function Capacity test (LiMAx) and 99mTc-mebrofenin SPECT/CT—with perioperative hemodynamic, oxidative and metabolic parameters. A narrative literature review was performed using PubMed and Web of Science, covering publications from January 2000 to January 2025. The search combined keywords and MeSH terms such as major hepatectomy, liver regeneration, hemodynamic optimization, oxidative stress and post-hepatectomy liver failure. We focused on clinically relevant studies, including randomized controlled studies and consensus guidelines, and complemented the search by screening the reference lists of selected articles. When direct clinical evidence was limited, a physiologically grounded interpretation was used to support a pragmatic framework for perioperative management. Results: The framework integrates three complementary physiological domains that together determine functional liver recovery. The first relates to hemodynamic stability, including optimal maintenance of arterial and venous pressures as well as portal-splanchnic gradients, which support adequate perfusion and oxygenation of hepatocytes. The second addresses the balance between oxidative stress and antioxidant defense, where the key indicators are the level of lipid peroxidation and endogenous antioxidant capacity. The third domain evaluates the functional ability of the liver through dynamic tests of synthesis and metabolism, such as factor V, indocyanine clearance (ICG-PDR), and the LiMAx test. With the integration of these three domains, a functional profile of liver recovery can be defined, facilitating monitoring of the physiological response in real time and guiding individualized perioperative support to the individual needs of the patient. Conclusions: Functional recovery follows a dynamic continuum, progressing from early reperfusion stress through hemodynamic stabilization to progressive hepatocellular regeneration. Integration of functional FLR assessment with perioperative physiological monitoring may support more individualized prediction of the regenerative capacity and therapeutic decision-making. This physiology-guided perspective extends assessment beyond remnant volume alone to include functional recovery. Full article

Background: Accurate prognostic stratification remains essential for optimizing outcomes in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). The hemoglobin–albumin–lymphocyte–platelet (HALP) score is a composite biomarker reflecting systemic inflammation, nutritional status, and immune competence, and has demonstrated prognostic value in several malignancies. This study aimed to evaluate the predictive utility of the HALP score for survivals and recurrence in HCC patients undergoing LT. Methods: A total of 476 consecutive patients who underwent LT for HCC between 2006 and 2024 were retrospectively analyzed. Pretransplant HALP scores were calculated for all patients. Receiver operating characteristic (ROC) analysis identified an optimal cut-off value of 29 for recurrence prediction. Patients were stratified into HALP ≥ 29 and HALP < 29 groups. DFS and recurrence rates were compared. Prognostic performance was assessed using the concordance index (C-index) and area under the ROC curve (AUC). Outcomes were further compared with the Milan and Expanded Malatya criteria. Results: Of the 476 patients, 335 (70.4%) had HALP ≥ 29 and 141 (29.6%) had HALP < 29. The HALP ≥ 29 group demonstrated significantly higher 5- and 10-year DFS rates compared with the HALP < 29 group (67.1% vs. 58.5% and 49.5% vs. 33.5%, respectively; p < 0.001). Recurrence rates were significantly lower in the HALP ≥ 29 group (14.0% vs. 31.9%; p < 0.001). However, patients within the Milan and Expanded Malatya criteria showed superior long-term DFS and lower recurrence rates in the HALP ≥ 29 compared to the HALP < 29 group (p ≤ 0.037). HALP ≥ 29 was associated with lower tumor burden parameters and improved hepatic functional reserve. Despite its significance, HALP demonstrated inferior discriminative performance (C-index: 0.565) compared with the Milan (0.621) and Expanded Malatya (0.648) criteria. Patients beyond the Milan criteria (n = 233) with HALP ≥ 29 achieved a 5-year overall survival of 54.2%, compared with 37.8% with HALP < 29. Conclusions: Low HALP score is associated with poor DFS and a high post-transplant recurrence rate. Although it represents a non-invasive and cost-effective biomarker, its prognostic accuracy remains inferior to established transplant selection criteria, limiting its use as a standalone selection tool. However, individuals beyond Milan with HALP ≥ 29 achieved survival outcomes exceeding internationally accepted post-transplant benchmarks. Incorporating HALP into pre-transplant evaluation may help identify a biologically favorable subgroup among patients traditionally considered high risk based solely on tumor burden. Full article

The transjugular intrahepatic portosystemic shunt (TIPS) is a cornerstone intervention for complications of portal hypertension, including variceal bleeding and refractory ascites. As the population with cirrhosis ages, clinicians increasingly face the question of whether and how to perform TIPS safely in older adults. We reviewed observational cohorts, registry analyses, and systematic reviews/meta-analyses. Existing evidence does not support chronological age as an absolute contraindication; however, multiple studies suggest that advanced age is associated with higher rates of post-TIPS hepatic encephalopathy (HE), early mortality, and readmissions. These findings underscore the need to shift from a binary “eligible vs. ineligible” paradigm to a structured, actionable framework that addresses modifiable risks and anticipates age-related vulnerabilities. Recent clinical practice guidance emphasizes comprehensive pre-TIPS assessment and vigilant post-procedure care, with specific attention to HE risk factors (e.g., prior HE, hyponatremia, renal dysfunction, sarcopenia) and cardiopulmonary reserve. In this narrative review, we propose an elderly-focused clinical pathway built around a four-domain assessment (Liver–Brain–Body–Heart/Kidney) and a traffic-light risk tiering system to guide patient selection, procedural strategy, follow-up scheduling, and triggered management of HE, cardiac decompensation, and renal dysfunction. This pathway aims to preserve the benefits of portal decompression while reducing preventable complications and improving outcomes that are meaningful to older patients, including functional status and quality of life. This narrative review emphasizes that outcomes after TIPS in older adults are determined not by chronological age alone but by multidomain physiological reserve. The proposed pathway informs patient selection, procedural planning, and early post-discharge monitoring in older adults. Full article

Background/Objectives: Acute exercise remodels many interconnected biochemical pathways in metabolically active tissues. This remodeling involves the activation of the energy-sensing AMP-activated protein kinase (AMPK) to maintain cellular energy homeostasis. Critical energy reserves of glycogen, primarily stored in liver and skeletal muscle and known to interact with AMPK, are utilized to help meet increased energy demands with exercise. However, the breadth of metabolic pathways regulated by acute exercise and AMPK’s interactive roles with glycogen remain incompletely understood. This study therefore aimed to map mouse liver and skeletal muscle metabolite responses to continuous acute exercise and disruption of AMPK-glycogen interactions. Methods: Liquid chromatography–mass spectrometry-based untargeted metabolomics was used to measure the relative abundance of liver and gastrocnemius muscle metabolites at rest and following an acute bout of continuous treadmill running in wild type (WT) and AMPK transgenic mice with double knock-in (DKI) mutations in the β subunit carbohydrate binding module that mediates glycogen binding. Results: Over 200 total metabolites were identified/annotated across liver and skeletal muscle, including 45 metabolites responsive to exercise (p < 0.05; FDR < 0.1). Exercise-regulated metabolites included known metabolic pathways and metabolites never associated or with only emerging evidence related to exercise (e.g., ergothioneine) and/or AMPK-glycogen interactions (N6,N6,N6-trimethyl-L-lysine, a precursor of L-carnitine). Conclusions: Liver and skeletal muscle metabolomic profiles displayed shifts between WT and DKI mice at rest, with shifts also detected following a continuous acute exercise bout. An interaction effect was also observed in skeletal muscle, suggesting differential muscle metabolite responses to acute exercise in DKI mice that may contribute to their functional impairments in metabolic control and exercise capacity versus WT. Collectively, these findings expand the molecular landscape of acute exercise and reveal liver and muscle metabolites underlying exercise-induced metabolic responses. Full article

Background: Transcatheter edge-to-edge repair (TEER) has emerged as an established treatment option for patients with severe mitral (MR) and tricuspid regurgitation (TR) who are at high surgical risk. Patients referred for TEER frequently present with advanced comorbidities, including cirrhosis or chronic liver disease (CLD). Hepatic dysfunction, driven by chronic venous congestion and impaired cardiac output, represents a key yet underrecognized determinant of prognosis in this population. The impact of TEER on hepatic function and outcomes in patients with advanced liver disease remains incompletely defined. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO. A comprehensive literature search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed up to 16 January 2026, without language restrictions. Studies evaluating mitral or tricuspid TEER in adult patients with cirrhosis, chronic or advanced liver disease, congestive hepatopathy, or cardiohepatic syndrome were included. Hepatic function was assessed using biochemical markers, clinical diagnoses, or composite scores such as Model for End-Stage Liver Disease (MELD) score and Model for End-Stage Liver Disease Excluding INR (MELD-XI). A qualitative synthesis was performed due to heterogeneity in study design and outcome reporting. Results: Twelve studies were included, comprising prospective and retrospective cohorts, registry-based analyses, mechanistic studies, and one illustrative case report. Six studies evaluated mitral TEER (M-TEER) and six tricuspid (T-TEER). Across both valve interventions, impaired baseline hepatic function was consistently associated with increased mortality and adverse clinical outcomes. MELD and MELD-XI scores emerged as robust prognostic markers following both M-TEER and T-TEER. Successful reduction in valvular regurgitation was associated with stabilization or improvement of hepatic parameters in selected patients, particularly after T-TEER. However, advanced cardiohepatic syndrome and limited hepatic reserve were linked to poor outcomes despite procedural success. Conclusions: Hepatic dysfunction is a powerful determinant of prognosis in patients undergoing M-TEER and T-TEER. While TEER may improve hepatic congestion and liver-related parameters in selected patients, outcomes are highly dependent on baseline hepatic reserve and global hemodynamic status. A personalized approach integrating hepatic assessment into patient selection and risk stratification is essential to optimize outcomes in this complex and growing population. Full article

Patients with hepatocellular carcinoma (HCC) often sit at the crossroads of malignancy and chronic liver disease, where impaired hepatic reserve, systemic inflammation, and treatment-related stress accelerate loss of skeletal muscle mass and function. In this narrative review, we synthesize current evidence on the two-way relationship between sarcopenia and HCC management across curative and palliative settings. We outline key biological pathways—altered energy substrate use, amino acid imbalance, hyperammonemia-related signaling, and inflammatory and hormonal perturbations—that promote progressive muscle wasting, and we summarize how sarcopenia influences tolerance, complications, and outcomes of surgery, locoregional therapies, and systemic agents. We then translate the literature into practical supportive-care principles, including adequate energy and protein delivery, optimized meal distribution (including late-evening snacks), and selected supplementation alongside hepatic rehabilitation/exercise. Potential adjuncts discussed include branched-chain amino acids, L-carnitine, vitamin D, zinc, and other micronutrients. Because the available data are heterogeneous and largely derived from observational cohorts or extrapolated from cirrhosis populations, HCC-specific randomized trials and standardized intervention protocols remain limited. Therefore, nutritional and exercise recommendations should be individualized according to tumor stage, hepatic function, comorbidities, and treatment goals, and viewed as supportive guidance that requires confirmation in well-designed prospective studies. Full article

Background/Objectives: Atezolizumab plus bevacizumab (Atz+Bev) is widely used for advanced hepatocellular carcinoma (HCC), yet predictors of post-progression survival (PPS), a clinically meaningful endpoint reflecting the feasibility of treatment sequencing, remain unclear. We aimed to identify determinants of PPS and factors associated with successful transition to subsequent therapy after progressive disease (PD) on Atz+Bev. Methods: We retrospectively analyzed 132 patients with HCC who initiated Atz+Bev with Child–Pugh A and Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1. PPS was defined as survival from radiological PD to death; tumor response was assessed by RECIST v1.1. Results: Among 132 patients treated with Atz+Bev, median progression-free and overall survival were 9.2 and 21.2 months. PD occurred in 97 patients, with a median PPS of 9.2 months. At PD, 76 patients (78.4%) maintained both Child–Pugh A and ECOG PS 0/1; 93.4% of these patients transitioned to subsequent therapy, compared with 38.0% of patients who did not maintain Child–Pugh A and ECOG PS 0/1. The median PPS values were 14.7 and 2.0 months, respectively (p < 0.0001). In this PD cohort, disease control achieved with subsequent therapy after radiological PD was associated with longer PPS (16.1 vs. 5.0 mosnths; p = 0.0002). ECOG PS 0, Child–Pugh A, absence of portal vein invasion, and AFP < 400 ng/mL at PD independently predicted prolonged PPS. A baseline Child–Pugh score of 5 independently predicted preservation of Child–Pugh A and ECOG PS 0/1 at PD. Conclusions: Initiating Atz+Bev under optimal liver function (Child–Pugh 5) and preserving hepatic reserve and performance status through progression are critical for enabling subsequent therapy and achieving longer PPS. Full article

Objectives: Rifaximin is a non-absorbable antibiotic that has an efficacy for hepatic encephalopathy (HE). We previously demonstrated that rifaximin improved liver functional reserve, but this was a single-center study with a limited number of cases, and there were few cases of long-term use. Here, we conducted a multicenter study to evaluate the efficacy of long-term rifaximin administration on the liver functional reserve. Methods: A multicenter retrospective study was conducted on cirrhotic patients who received rifaximin for more than 12 months. We evaluated the efficacy of long-term rifaximin administration on the liver functional reserve. Results: A total of 65 cirrhotic patients were enrolled. Administration of rifaximin for 12 months significantly improved the Child–Pugh score (CPS) and albumin–bilirubin (ALBI) score. Regarding the parameters of the CPS, albumin scores significantly improved in addition to HE scores at 12 months. Univariate and multivariate analysis revealed that high C-reactive protein (CRP) levels (>0.69 mg/dL) at baseline were the predictive factor for improvement in the liver functional reserve. Conclusions: This study suggests that long-term rifaximin administration may improve the liver functional reserve in cirrhotic patients through improvement in albumin levels. CRP levels predict improvement in the liver functional reserve. Full article

The liver has a notable regenerative capacity, primarily through hepatocyte proliferation. However, when this process is impaired—due to severe and/or chronic injury—liver progenitor cells (LPCs) serve as a facultative reserve to restore hepatic function. LPCs, which are a bipotent and heterogeneous population located near the canals of Hering, can differentiate into hepatocytes and cholangiocytes. Recent evidence suggests that LPCs may originate from mature hepatic cells—such as hepatocytes, cholangiocytes, and hepatic stellate cells—through dedifferentiation under specific injury conditions. Cellular plasticity in the liver is governed by complex signaling networks that regulate LPC activation, maintenance, and lineage commitment. However, the precise cellular origin of LPCs and the mechanisms driving their activation remain incompletely defined. Therefore, this review aims to synthesize current insights into LPC biology and emphasize their diverse cellular origins, functional roles in liver regeneration, and the key signaling pathways involved. A deeper understanding of LPC dynamics may ultimately guide the development of novel therapeutic strategies to enhance liver regeneration in chronic liver disease. Full article

Background and Objectives: The extracellular volume fraction (fECV) of the liver, as measured by contrast-enhanced computed tomography (CT), has been shown to correlate closely with the histological stages of hepatic fibrosis. This study aimed to investigate the diagnostic performance of a liver extracellular volume fraction derived from dual-energy CT (DECT) for evaluating liver functional reserve based on the Child–Pugh class in cirrhotic patients, compared with other noninvasive markers. Materials and Methods: This retrospective study included 258 patients with liver cirrhosis who underwent contrast-enhanced DECT. The fECV was measured using iodine maps derived from equilibrium phase images obtained 3 min after contrast injection at 100/140 Sn kVp. Statistical analyses included Welch’s ANOVA with post hoc tests, Spearman’s correlation, and ROC analysis. The area under the curve (AUC) was compared among fECV and other noninvasive markers (aspartate transaminase to platelet ratio index [APRI], Fibrosis-4 [FIB-4], and model for end-stage liver disease [MELD]) using DeLong’s test. Intra- and interobserver reliability of fECV was assessed with the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) for differentiating Child–Pugh classes was compared among the fECV and other noninvasive markers (aspartate transaminase to platelet ratio index [APRI], Fibrosis-4 [FIB-4], and model for end-stage liver disease [MELD]). Results: The fECV increased significantly with advancing Child–Pugh classes (p < 0.001), showing a moderate correlation with Child–Pugh class (r = 0.53). The mean differences in fECV among the Child–Pugh classes were 8.88 between A and B (95% confidence interval [CI], 5.85–11.92; p < 0.001) and 7.42 between B and C (95% CI, 1.92–12.91: p < 0.001). The AUC for differentiating Child–Pugh classes A and B demonstrated no significant differences among the fECV (0.84), APRI (0.83, p > 0.99) and FIB-4 (0.83, p > 0.99), except for MELD, which had a significantly higher AUC (0.94, p = 0.047). For differentiating Child-Pugh classes B and C, the fECV demonstrated a significantly higher AUC (0.78), compared with FIB-4 (0.50, p = 0.038) and APRI (0.49, p = 0.037), whereas no significant difference was observed between fECV and MELD (0.92, p = 0.12). The intra- and interobserver reliabilities of the fECV measurements were excellent (ICC, 0.93; 95% CI, 0.91–0.95 and 0.91; 95% CI, 0.88–0.92, respectively). Conclusions: DECT derived fECV is a useful noninvasive marker for assessing liver functional reserve based on the Child–Pugh classification. Full article

As a synthetic analogue of vasopressin, desmopressin or DDAVP has well established hemostatic properties. We present a review of DDAVP and summarize the clinical and laboratory evidence for its use in hemophilia A, von Willebrand disease (VWD), platelet function disorders, uremia, liver cirrhosis, and pregnancy, followed by illustrative examples of its broad efficacy from our local practice. In brief, DDAVP acts to release von Willebrand factor (VWF) and factor VIII from endogenously stored reserves, thereby correcting plasma deficiencies present in mild to moderately affected patients with hemophilia A and VWD. Thus, DDAVP represents a non-transfusional therapy for these disorders. Typically, a trial of DDAVP is arranged to assess individual responsiveness before employing DDAVP clinically, since there is individual variation in responsiveness. Thereafter, DDAVP can be utilized in responsive patients for clinical use and provides a factor replacement sparing strategy in these patients for some clinical situations. Nevertheless, DDAVP is best applied as a factor replacement sparing strategy, especially for minor procedures or short-term use. Full article

Liver failure, both acute and chronic, represents a complex, life-threatening condition frequently requiring intensive care unit (ICU) admission. Nutritional management is a crucial component of supportive therapy, aiming to mitigate catabolism, preserve lean body mass, and support immune and organ function. In acute liver failure (ALF), early nutritional intervention within 24–48 h and individualized energy–protein prescriptions are essential, even in the presence of hepatic encephalopathy. Chronic liver failure (CLF) and acute-on-chronic liver failure (ACLF) are often associated with severe malnutrition, sarcopenia, and systemic inflammation, necessitating tailored nutritional strategies. Subjective Global Assessment (SGA) and Royal Free Hospital Global Assessment (RFH-GA) tools are instrumental in identifying nutritional risk. Enteral nutrition (EN) is preferred across all stages, with parenteral nutrition (PN) reserved for contraindications. Special considerations include micronutrient repletion, prevention of refeeding syndrome, and perioperative nutritional support in transplant candidates and recipients. This clinical overview summarizes current evidence and guidelines on ICU nutrition in liver failure, emphasizing a multidisciplinary approach to improve outcomes. Full article

Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy, with the treatment for transplant-ineligible localized disease traditionally relying on locoregional therapies, such as surgical resection, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). Systemic therapy has historically been reserved for advanced, unresectable HCC. However, lenvatinib, an oral multikinase inhibitor, has recently gained traction as part of a multimodal approach for localized HCC in combination with locoregional treatments. An upfront TACE or TARE can induce tumor hypoxia, leading to the upregulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which promotes tumor angiogenesis and progression. The rationale for combining lenvatinib with a locoregional therapy is to enhance tumor shrinkage while preserving liver function before a definitive intervention. Clinical trials, such as TACTICS and LAUNCH, have demonstrated improved outcomes with this approach. Additionally, retrospective studies, including those incorporating immune checkpoint inhibitors, have reported further benefits. This review explores the combination of lenvatinib with various locoregional modalities, including TARE, microwave ablation (MWA), and radiofrequency ablation (RFA), highlighting their indications and clinical outcomes. Furthermore, we discuss the ongoing and upcoming clinical trials investigating the integration of systemic agents with locoregional therapies for intermediate-stage HCC, including EMERALD-1, EMERALD-3, LEAP-012, and CheckMate 74W. Full article