Search Results (539)

Background/Objectives: To evaluate the incidence of rapid recurrence within 6 months of curative resection for hepatocellular carcinoma (HCC) and to identify preoperative gadoxetic-acid-enhanced MRI features associated with rapid recurrence (<6 months) in the entire cohort. Methods: This retrospective study included 200 patients who underwent curative resection for HCC and had preoperative gadoxetic-acid-enhanced MRI between January 2016 and December 2023. Patients were categorized into a rapid recurrence group (n = 21) and a non-rapid recurrence group (n = 179). Preoperative MRI features, including tumor size, multiplicity, tumor margin, arterial peritumoral enhancement, peritumoral hepatobiliary phase (HBP) hypointensity, diffusion restriction, apparent diffusion coefficient (ADC) values, and presence of non-hypervascular hepatobiliary phase hypointense nodule (NHHN), were evaluated. Univariate and multivariate Firth penalized logistic regression analyses were performed. Results: Rapid recurrence occurred in 10.5% (21/200) of patients (median, 4.0 months). Multivariate analysis revealed that larger tumor size (odds ratio [OR], 1.25 per 1-cm increase; p = 0.012) and the presence of NHHN (OR, 11.30; p < 0.001) were independent predictors of rapid recurrence. A nomogram incorporating these features demonstrated excellent discriminative performance, with a bootstrap-corrected area under the curve (AUC) of 0.864 (95% CI, 0.791–0.922). Conclusions: The presence of NHHN and larger tumor size on preoperative MRI were associated with rapid recurrence (<6 months) after curative resection for HCC. These findings may provide additional support for preoperative risk stratification and the planning of postoperative surveillance strategies. Full article

Background/Objectives: The prognostic significance of body mass index (BMI) in hepatocellular carcinoma (HCC) remains controversial, and whether the obesity paradox may reflect tumor biology or host-related factors is unclear. This study evaluated the association between BMI and survival after curative hepatic resection using continuous and interaction-based analyses. Methods: We retrospectively analyzed 1349 patients who underwent curative hepatic resection for HCC between 2004 and 2021. BMI was assessed both categorically (low (<18.5 kg/m²), normal (18.5–24.9 kg/m²), and high (≥25 kg/m²)) and as a continuous variable. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier methods and multivariable Cox proportional hazards models. Interaction terms were incorporated to examine whether the prognostic effect of BMI varied across clinically relevant subgroups defined by tumor differentiation, tumor size, tumor number, and alpha-fetoprotein level. Results: OS differed significantly across BMI categories (log-rank p < 0.001), whereas differences in RFS were modest. At 3 years, estimated OS rates were 88%, 82%, and 62% in the high, normal, and low BMI groups, respectively. In multivariable analysis, higher BMI as a continuous variable was independently associated with improved OS (hazard ratio per 1-unit increase, 0.87; 95% confidence interval, 0.79–0.95; p = 0.005), but not with RFS. Subgroup analyses demonstrated a consistent protective association between BMI and OS without significant interactions across tumor-related factors. Conclusions: Higher BMI is independently associated with improved overall survival after hepatic resection for HCC, irrespective of tumor biology. These findings support a host-related explanation for the obesity paradox in surgically treated HCC. Full article

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, and its management is limited by heterogeneous risk profiles, suboptimal surveillance performance, diagnostic uncertainty in chronically diseased livers, and difficulty individualizing prognosis after treatment. The aim of this narrative review was to critically evaluate artificial intelligence (AI) applications across the HCC care continuum, with emphasis on their intended clinical role, reported performance, evidence maturity, and barriers to implementation. A major strength of this review is that it moves beyond a descriptive catalog of models by structuring the literature around clinically relevant decision points and by explicitly distinguishing emerging proof-of-concept tools from applications with stronger translational potential. Across risk stratification, surveillance, imaging-based diagnosis, pathology, treatment-response prediction, and prognostication, we found that AI consistently demonstrates promise, particularly for identifying patients at higher future HCC risk, improving lesion detection and characterization on ultrasound, CT, MRI, and contrast-enhanced ultrasound, assisting histopathologic classification, and predicting outcomes such as microvascular invasion, recurrence, survival, and response to locoregional therapies. However, we also found that the evidence base remains highly uneven: many diagnostic studies are retrospective and lesion-enriched rather than embedded in true surveillance populations, many prognostic models lack robust external validation and calibration assessment, and reference standards, imaging protocols, and dataset composition vary substantially across studies. These findings are clinically relevant because they highlight both where AI may offer near-term value and why most published systems are not yet ready for routine use. Overall, AI in HCC should be viewed as a rapidly evolving but still transitional field. Its future impact will depend not only on higher-performing algorithms but on clearly defined clinical use cases, multicenter and prospective validation, transparent reporting, workflow-aware evaluation, and implementation strategies that support safe, equitable, and scalable adoption. Full article

Background/Objectives: Natural killer (NK) cells are essential mediators of innate immune defense and play a key role in tumor surveillance following liver transplantation (LT). Despite this, the prognostic relevance of pre-transplant NK cell activity in living donor LT (LDLT) has not been fully established. Methods: This retrospective analysis included 134 adult patients who underwent LDLT. NK cell activity was evaluated prior to transplantation using interferon-γ release assays and classified as low (<10 pg/mL) or high (≥10 pg/mL). Overall survival (OS) was assessed for all participants, whereas recurrence-free survival (RFS) was analyzed patients with HCC. Results: Patients classified as having high NK activity (≥10 pg/mL) experienced significantly better overall survival compared to those with low activity (log-rank p = 0.032). In the multivariate analysis, high NK activity showed a strong trend toward improved overall survival (HR, 0.52; 95% CI, 0.26–1.04; p = 0.063). Among recipients with HCC, high NK activity was associated with a markedly improved recurrence-free survival (log-rank p = 0.004). Multivariate Cox regression further established NK activity as an independent factor for tumor recurrence (HR, 0.27; 95% CI, 0.08–0.87; p = 0.028). Conclusions: Pre-transplant NK cell activity independently predicts both survival and recurrence following LDLT. Full article

Background and Objectives: Reliable tools for evaluating tumor biology and forecasting clinical outcomes in recurrent hepatocellular carcinoma (HCC) remain scarce, and molecular characterization through genetic profiling is equally limited in this setting. This investigation explores whether serum tumor marker expression patterns correlate with genomic mutation profiles, and whether such correlations may facilitate more accurate prediction of tumor biology and patient prognosis in recurrent HCC. Materials and Methods: We analyzed a cohort of 20 patients who underwent curative-intent resection for both primary and recurrent HCC. Tumor specimens collected at the time of each operation were subjected to targeted next-generation sequencing for mutation profiling. Based on pre-operative serum levels of AFP (alpha-fetoprotein) and PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) measured before each surgery, patients were stratified into four biomarker subgroups. Those who maintained the same biomarker subgroup at both operations were designated the ‘serum concordant group’, whereas those who transitioned between subgroups were classified as the ‘serum discordant group’. Clinical characteristics and mutation data were subsequently compared between these two classifications. Results: The interval from primary surgery to disease recurrence was significantly shorter in the serum concordant group relative to the serum discordant group (mean 11.16 ± 1.86 vs. 44.8 ± 9.45 months, p < 0.001). Additionally, disease-free survival following reoperation was significantly inferior in the concordant group compared with the discordant group (p = 0.039). Regarding mutational patterns, the concordant group demonstrated shared gene mutations between primary and recurrent lesions, while the discordant group exhibited divergent mutational landscapes across both timepoints. Conclusions: The concordance or discordance of serum tumor marker profiles between primary and recurrent HCC lesions may serve as a clinically accessible surrogate for underlying tumor biology and prognostic stratification. These results are preliminary and hypothesis-generating. Further studies in larger, independent cohorts are warranted to confirm the observed associations. Full article

Objective: An important characteristic of Hepatocellular carcinoma (HCC) is that it features multicentric recurrences that can recur after curative treatment. Current recommended curative treatments for HCC include liver transplantation (LT), and prognostic evaluation and appropriate treatment selection are crucial in the management of HCC patients. Factors considered tend to include tumor size and number, lobar distribution, multinodularity, α-fetoprotein (AFP) level, degree of tumor differentiation, vascular invasion, and satellite nodules. However, the prognostic value of intrahepatic lymphatic vessel invasion (LVI) has rarely been reported for liver cancers. Methods: From January 2012 to December 2020, a total of 178 HCC patients who underwent liver transplantation consecutively were retrospectively enrolled. Those who underwent liver transplantation were divided into two groups based on the presence or absence of lymphatic vessel invasion. The primary aim was to compare the two groups for overall survival (OS), disease free survival (DFS), and recurrence rates, as well as to evaluate the prognostic effect of LVI after transplantation. Results: Poor tumor characteristics such as high tumor differentiation grade and MVI were significantly higher in the patient group with LI. Tumor recurrence and mortality rates were significantly higher in LI-positive recipients. Conclusions: The lymphatic invasion (LI) group displayed higher rates of recurrence and mortality. The findings emphasize the need to incorporate LI assessment into prognostic evaluations to enhance the management and outcomes of individuals with Hepatocellular carcinoma. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and liver transplantation (LT) remains the only curative treatment addressing both tumor burden and underlying liver disease. Despite an adequate candidate selection, HCC recurrence after LT occurs in 8–20% of cases and is associated with a poor prognosis, particularly in patients who experience an early relapse. The management of HCC recurrence remains particularly challenging due to the lifelong immunosuppression required after LT, which may promote tumor progression and restrict therapeutic options. This review synthesizes the current evidence on systemic therapies for recurrent HCC after LT, focusing on tyrosine kinase inhibitors (TKIs), immunotherapy, and the current available immunosuppression strategies. Unfortunately, in this setting, robust prospective studies are lacking, and clinical decision-making remains based on retrospective data and expert consensus. Future research should prioritize the prospective evaluation of systemic regimens, integration of immunosuppression modulation, and careful exploration of immunotherapy or new target therapies in this special population. Full article

The integration of artificial intelligence (AI) into medicine, oncology, and radiology represents a marked shift in the diagnosis, prognostication, and management of hepatocellular carcinoma (HCC), a malignancy with high global incidence and poor prognosis. This review examines the application of AI, including machine learning (ML) and deep learning (DL), across the spectrum of HCC care. As AI advances, new convolutional neural networks (CNNs) and other models are enhancing diagnostic accuracy, reducing interpretation times, and improving the characterization of liver lesions across major imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Beyond diagnosis, the transformative role of AI in prognostication is also improving, where AI can now noninvasively predict critical factors such as microvascular invasion, genetic mutation status, tumor recurrence, and treatment response. Furthermore, AI has shown promise in facilitating patient-specific treatment planning by stratifying patients for interventions such as transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT). The review also addresses the emerging fields of pathomics and the use of AI in positron emission tomography (PET), while critically evaluating the cost-effectiveness of these technologies. Despite its promise, the widespread clinical adoption of AI faces challenges, including limited generalizability, maintaining patient privacy, ethical considerations, and the need for robust prospective validation. Ultimately, this review illustrates that the future of HCC management lies in a collaborative, hybrid-intelligence model, where AI-driven insights augment clinical expertise to optimize diagnostic pathways, personalize therapy, and improve patient outcomes. Full article

Protein Kinase N1 (PKN1) is a PKC-related serine/threonine kinase of the AGC group within the eukaryotic protein kinase superfamily (ePK) that orchestrates oncogenic, metabolic, and cytoskeletal signaling. Despite these critical roles, the phosphorylation-dependent regulatory network of PKN1 remains largely undefined. We performed a large-scale phosphoproteomic data integration of publicly available human datasets (892 profiling datasets and 191 differential datasets) to identify recurrent PKN1 phosphorylation sites. This analysis identified two predominant PKN1 phosphosites, S562 and S916, that were frequently observed and differentially regulated across studies. The S916 maps to a turn motif (TM) in the AGC group of kinases, which is evolutionarily conserved among PKN paralogs, while S562 is non-conserved and appears to be PKN1-specific. Co-regulation and enrichment analyses suggest that S916 is associated with insulin/AMPK signaling and metabolic pathways, whereas S562 co-occurs with phosphosites involved in cell division, cytoskeletal regulation, and microtubule cytoskeleton organization. Integrating predicted and experimentally validated kinases, substrates, and interactors, we reconstructed a phospho-regulatory network that positions PKN1 at the crossroads of cytoskeleton organization and metabolic signaling. To assess the disease relevance of these phosphorylation events, we integrated transcriptomic and phosphoproteomic data from the hepatocellular carcinoma database (HCCDB). PKN1 was markedly up-regulated in HCC, and its phosphorylation at S916 was positively co-regulated with multiple oncogenic and proliferation-associated protein phosphosites. These results predict S562 and S916 as potential sites for targeted biochemical validation and functional experiments. The identification of S562 and S916 as key regulatory sites provides new mechanistic insight into PKN1 activation and highlights potential avenues for therapeutic targeting. Full article

Background and Aim: Adjuvant therapy after curative intent treatment for hepatocellular carcinoma (HCC) is a significant unmet need. The IMbrave050 study demonstrated improved recurrence-free survival (RFS) in patients with high-risk HCC receiving adjuvant atezolizumab and bevacizumab post-curative treatment compared to active surveillance. However, the IMbrave050 cohort was predominantly Asian, largely underwent surgical resection, and had chronic liver disease (CLD) mainly due to hepatitis B features that differ markedly from the Australian setting, where microwave ablation (MWA) is more common and hepatitis B-related CLD is less prevalent. Given these differences, this study aimed to explore the performance of the IMbrave050 risk criteria in an Australian population of patients with early-stage HCC undergoing curative treatment to determine if the criteria identified patients with a high risk of recurrence who may benefit from adjuvant treatment. Method: We performed a retrospective 5-year study of 50 patients with early-stage HCC undergoing MWA with curative intent or liver resection. Patients were stratified into high- and low-risk groups using the IMbrave050 criteria. The primary outcomes were RFS and overall survival (OS) in the high- and low-risk cohorts. Results: For patients who underwent liver resection, the 1-year RFS was 77.8% and 100% in high- and low-risk patients respectively (p = NS). In those who underwent MWA, the 1-year RFS was 89.5% in the high-risk cohort and 73.3% in the low-risk cohort (p = NS). OS at 1-year was 100% in all cohorts (p = NS). Conclusions: In this Western cohort receiving predominantly ablation as curative therapy the current high-risk criteria do not reliably distinguish between those with increased risk of early recurrence and those without. Criteria defining high-risk may need to be refined to better identify patients who may benefit from adjuvant therapy in this setting. Full article

Background: Hepatocellular carcinoma (HCC) is a major cause of mortality in the United States, but it can be cured with orthotopic liver transplant (OLT) in selected patients. Despite curative intent, post-OLT recurrence can occur in up to 15% of patients. The need for a program of post-OLT surveillance is widely accepted but the specifics of an optimal program have not been established. There is interest in identifying lower-risk cohorts of patients in whom an abbreviated strategy of surveillance may prove adequate, utilizing tools such as the RETREAT score. Unique challenges are posed in the post-transplant population regarding safety and tolerability of systemic therapy for HCC recurrence, suggesting early detection is beneficial. Methods: This was a single-center retrospective analysis of characteristics and outcomes for all patients undergoing transplant at our center between 1 January 2012 and 31 December 2024. Diagnosis of HCC was determined by histological confirmation or Liver Imaging and Reporting Data System (LI-RADS) 5 findings on contrast-enhanced cross-sectional imaging. RETREAT scores were calculated for all patients. Results: During the study period, 923 transplants were performed, of which 329 (35.6%) were for HCC. Post-OLT recurrence occurred in 36 (10.9%) of these. Recurrence was associated with the presence of any viable tumor on explant surgical pathology, the presence of a viable tumor beyond Milan Criteria, the presence of microvascular invasion, a larger diameter of viable tumor on explant, and a higher RETREAT score. Although higher RETREAT scores were associated with post-OLT recurrence, one-third of patients who experienced post-OLT recurrence had RETREAT scores of 0 or 1. RETREAT scores did not correlate with the time interval between transplant and HCC recurrence. Systemic therapy proved challenging, with 10/25 patients receiving systemic therapy for post-OLT recurrence having to stop or alter regimens due to the severity of adverse effects. Conclusions: The rates of post-transplant recurrence and the experience of patients managed with systemic therapy for post-OLT recurrence in our experience were in line with previously published data. Due to the overall low RETREAT scores, the sensitivity of the RETREAT score in identifying patients at risk for post-OLT recurrence was limited, and the low RETREAT score had very limited incremental negative predictive value for identifying a low-risk population. This suggested that a broad screening strategy for post-OLT recurrence may be better than a personalized strategy in which patients with low RETREAT scores receive abbreviated surveillance. Full article

Background: Liver transplantation (LT) for Hepatocellular carcinoma (HCC) is still burdened by a significant risk of tumor recurrence. The aim of this study was to apply the Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for prediction of HCC recurrence and survival. Methods: This retrospective study included all adult patients who consecutively underwent LT for HCC from January 2000 to July 2022 at a single institution. Results: During a median follow-up of 64 months, 56 (19%) out of 298 patients [54%, 36% and 10% with a RETREAT score equal to 0/1 (low), 2/3 (medium) and 4–6 (high), respectively] experienced HCC recurrence after a median of 31 months. The HCC recurrence rates at 1, 5 and 10 years were respectively 4%, 16% and 23%. The 5-year RFS for low-, medium- and high-risk groups were 93%, 78% and 58% (p < 0.001), respectively. In the competitive risk analysis, the medium- and high-risk RETREAT groups had respectively a 2.3 HR (p = 0.017) and 6.4 HR (p < 0.001) of HCC recurrence compared with the low-risk group. Overall, 119 patients died [32 (27%) due to HCC recurrence], and the 5-year survival was 74% (95%, 86% and 61% for low-, medium- and high-risk groups, respectively). In the multivariate analysis, the RETREAT score was associated with the overall survival only for the highest risk class, which yielded a 2.5 HR of death compared with the lowest risk categories (p < 0.001). Conclusions: This study validates the RETREAT score and confirms its ability to predict the risk of HCC recurrence. Full article

Background and aims: Liver transplantation is effective against hepatocellular carcinoma (HCC), but recurrence remains a challenge. Traditional criteria based on tumor size, nodule number, and AFP levels have had limited success in predicting aggressiveness. [18F]FDG PET/CT has shown promise in identifying high-risk tumor features, including microvascular invasion (MVI), which is a key predictor of recurrence. Methods: In this retrospective, single-center study, all consecutive patients who underwent LT for HCC between 2010 and 2019 were included. Prior to listing, the patients underwent [18F]FDG PET/CT, and explant pathology was analyzed for MVI and other histological features. The primary objective was to identify the predictors of early HCC recurrence (within 24 months after LT). Secondary objectives included identifying predictors of high-risk histological features of the explant, describing recurrence patterns, and assessing post-recurrence survival. Results: The study included 143 patients (median age 59 years [IQR 54–64], 85% males, median MELD 10 [IQR 8–14], median AFP value 8.5 [IQR 4–39] ng/mL) and 40 (28%) with intra-hepatic [18F]FDG PET/CT positivity. HCC recurred post-LT in 25 patients (17%) (median post-LT follow-up 49 months [IQR 28.5–77]) and within 24 months in 12 patients (48%). MVI at the explant stage was independently associated with early recurrence (HR: 7.20, 95% CI 1.82–28.45, p = 0.005), while intra-hepatic [18F]FDG PET/CT positivity before LT independently predicted MVI in explants (OR 3.90, 95% CI 1.30–11.71, p = 0.01). Conclusions: [18F]FDG PET/CT may offer a valuable tool for pre-transplant risk assessment by identifying MVI, which is an independent predictor of early cancer recurrence. Its incorporation into the selection criteria for LT may enhance patient stratification and post-transplant outcomes. Full article

Background and Objectives: Gastric cancer is an aggressive malignancy characterized by high recurrence rates, even following curative resection. The Albumin–Bilirubin (ALBI) score was originally established to assess hepatic functional reserve in patients with hepatocellular carcinoma (HCC). By reflecting both systemic inflammation and nutritional status, the ALBI score has demonstrated significant prognostic utility across a spectrum of solid malignancies. The present study aimed to evaluate the prognostic significance of the ALBI score in gastric cancer patients receiving adjuvant therapy after curative-intent resection. Materials and Methods: This retrospective study included 168 patients with gastric cancer who underwent curative-intent resection followed by adjuvant therapy between November 2008 and January 2021. ALBI scores were calculated from pre-treatment serum albumin and bilirubin levels. Patients were dichotomized into ALBI Grade 1 and ALBI Grade 2 based on an optimal ROC-derived cut-off value of −2.60. Survival outcomes, including overall survival (OS) and recurrence-free survival (RFS), were estimated using the Kaplan–Meier method and compared via the log-rank test. Independent prognostic factors were identified using univariate and multivariate Cox proportional hazards regression models. Results: Of the 168 patients, 56.5% were classified as ALBI Grade 1 and 43.5% as ALBI Grade 2. ALBI Grade 2 was associated with significantly shorter median RFS (18.7 vs. 72.2 months; p = 0.001) and OS (40.7 vs. 104.3 months; p = 0.003). Multivariable analysis identified ALBI Grade 2 as an independent predictor for both poor OS (HR: 1.699, p = 0.010) and RFS (HR: 1.767, p = 0.004). Pathological stage III disease was also a significant independent prognostic factor for OS (HR: 3.024) and RFS (HR: 3.049) (all p = 0.010). Additionally, elevated CEA correlated with shorter RFS (p = 0.023). Conclusions: The ALBI score is a prognostic marker for both overall and recurrence-free survival in gastric cancer patients receiving adjuvant therapy. A lower ALBI score is associated with longer survival outcomes. The ALBI score may support postoperative risk stratification and individualized follow-up planning. Full article

Background/Objectives: Telomere dysfunction and the shelterin complex are implicated in cancer, yet the specific functions and interactions of telomerase and shelterin genes in hepatocellular carcinoma (HCC) tumorigenesis remain poorly understood. This study aims to investigate the clinico-biological functions and collaborative contributions of telomerase and shelterin components in hepatocarcinogenesis. Methods: We analyzed tumor and matched non-tumor tissues from 274 HCC patients who underwent hepatectomy. Telomere-related parameters, including TERT (telomerase reverse transcriptase) expression and telomere length measured by qRT-PCR, telomerase activity assessed by the Telomerase Repeated Amplification Protocol assay, and six shelterin components analyzed by RNA sequencing, were correlated with clinicopathological features. siRNA-mediated knockdown of TPP1 (POT1–TIN2 organizing protein) was performed to evaluate its regulatory effect on TERT expression. Findings were externally validated. Results: TERT and TPP1 were upregulated in tumors with increased telomerase activity and shortened telomere length. Among the shelterin components, TPP1 showed the strongest correlation with TERT, and its expression increased with tumor multiplicity and advancing stage. TPP1 expression also correlated with proliferation-associated genes, consistent with Gene Set Enrichment Analysis suggesting TPP1 involvement in proliferative activity. TPP1 knockdown suppressed TERT protein expression and inhibited HCC cell proliferation, with the strongest anti-proliferative effect observed after dual TERT–TPP1 knockdown. Clinically, high TPP1 expression was associated with significantly earlier HCC recurrence, and co-high expression of TPP1–TERT was linked to significantly worse survival after hepatectomy. Conclusions: The TERT–TPP1 axis enhances proliferative activity and is associated with aggressive features and poor outcomes in HCC. TPP1 represents a potential therapeutic target and prognostic biomarker for HCC. Full article