Liver transplantation (LT) provides the best long-term survival outcomes for patients with liver cancer. As a result, the field of transplant oncology has grown greatly over the past few decades, and many centers have expanded their criteria to allow increased access to LT for liver malignancies. Center-level guidelines and practices in transplant oncology significantly vary across the world, leading to debate regarding the best course of treatment for this patient population. An international consensus conference was convened by the International Liver Transplantation Society and the International Liver Cancer Association on February 1-2, 2024, in Valencia, Spain to establish a more universal consensus regarding LT for oncologic indications. The conference followed the Delphi process, followed by an external expert review. Consensus statements were accepted regarding patient assessment and waitlisting criteria, pretransplant treatment (including immunotherapy) and downstaging, living donor LT, post-LT patient management, and patient- and caregiver-related outcomes. The multidisciplinary participants in the consensus conference provided up-to-date recommendations regarding the selection and management of patients with liver cancer being considered for LT. Although participants deferred to center protocols in many cases, there was great interest in safely expanding access to LT for patients with larger tumor burden and biologically amenable lesions.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern-day practice-changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern-day practice-changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient-oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.

Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplant worldwide. While liver transplantation offers a survival advantage for early-stage HCC patients, post-transplant recurrence remains a significant concern, affecting up to 15% of recipients. We sought to conduct a comprehensive review related to HCC recurrence after liver transplant. Tumor-related factors such as poor differentiation, vascular invasion, and elevated tumor biomarkers like alpha-fetoprotein are key predictors of recurrence. Donor-related factors, including graft type and surgical procedures, can also influence outcomes, though their effects are less conclusive. Advancements in patient selection criteria and scoring systems, such as the Milan Criteria and RETREAT score, have improved risk stratification by incorporating tumor size, biomarkers, and response to pre-transplant treatment. Despite these measures, recurrent HCC after transplantation poses treatment challenges. Curative approaches such as resection are feasible for localized or oligometastatic recurrence and offer the best outcomes when applicable. Locoregional treatments, including ablation and transarterial chemoembolization, provide options for unresectable cases but have limited long-term efficacy. Systemic therapies, including targeted agents like sorafenib, regorafenib, and lenvatinib, have shown modest benefits in managing advanced recurrent HCC. Emerging immunotherapy approaches hold promise but face unique challenges due to the required immunosuppression in transplant recipients. Multidisciplinary evaluation remains essential for tailoring treatment plans. Future efforts should focus on refining predictive tools and exploring novel therapies to improve survival outcomes for patients with recurrent HCC after liver transplantation.

In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria, liver transplantation (LT) is an effective therapy. This study aims to define the survival-related molecular biological features helping precisely identifying the patients with HCC beyond the Milan criteria who have acceptable outcomes. In the derivation cohort, integrated analyses of tumor tissues are conducted using RNA sequencing (RNA-seq), proteomic landscape, and transposase-accessible chromatin sequencing (ATAC-seq). Based on transcriptomics, three subgroups that significantly differ in overall survival were identified in the derivation cohort, and these findings are validated in an independent cohort. In-depth bioinformatics analysis using RNA-seq and proteomics reveals that the promotion of cancer stemness by cancer-associated fibroblasts (CAFs) can be responsible for the negative biological characteristics observed in high-risk HCC patients. The ATAC-seq identifies key factors regulating transcription, which may bridge CAF infiltration and stemness. Finally, we demonstrate that the CAF-derived CXCL12 sustains the stemness of HCC cells by promoting XRCC5 through CXCR4.

Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres.

A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma.

Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored.

Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.

To explore the emerging use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients eligible for liver transplantation (LT), particularly as bridging and downstaging therapies. This review also addresses the clinical challenges of integrating ICIs into transplant protocols, including graft rejection, immune-related toxicities, and gaps in evidence.

ICIs have shown potential as bridging and downstaging therapies before LT, with multicentric studies reporting 75.6% successful downstaging, 85% 3-year post-LT survival, and 7.2% rejection-related mortality. A washout interval >94 days and older age have been identified as protective factors against allograft rejection. Combining locoregional therapies with ICIs has proven effective in the EMERALD-1 and LEAP-012 trials, which demonstrated improved progression-free survival (15.0 and 14.6 months, respectively) with ICI-TACE combinations. Similarly, the STAR-FIT phase II trial, combining TACE, SBRT, and avelumab, showed a 42% complete response rate and 12% conversion to curative therapy. Toxicity and rejection risk remain major challenges.

ICIs represent a promising tool for expanding transplant eligibility in HCC, but their integration into LT pathways remains complex. Safety concerns, particularly regarding timing and immune modulation, require careful evaluation. Prospective studies and biomarker development are needed to guide clinical decision-making. Novel therapies such as CAR-T cells may offer more targeted approaches in the future.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Multiple treatment modalities are available for the management of HCC, depending on its stage as determined by the Barcelona Clinic Liver Cancer staging system. Because liver transplantation (LT) theoretically removes the cancer and replaces the organ at risk for future malignancy, LT is often considered the most definitive and one of the most efficacious treatment options for HCC. Nevertheless, the success and efficacy of liver transplantation depend on various tumor characteristics. As a result, multiple criteria have been developed to assess the appropriateness of a case of HCC for LT, with the pioneering Milan Criteria established in 1996. Over the past 20 to 30 years, these criteria have been critically evaluated, expanded, and often liberalized to make LT for patients with HCC a more universally applicable option. Furthermore, the development of other treatment modalities has enabled downstaging and bridging strategies for HCC prior to LT. In this narrative and comprehensive review, we provided an update on recent trends in the epidemiology of HCC, selection criteria for LT, implementation of LT across different regions, treatment modalities available as bridges, downstaging strategies, alternatives to LT, and, finally, post-LT surveillance.

Primary and secondary liver cancers are frequently unresectable at the time of diagnosis. Historically, these patients were treated with palliative therapy and no hope for curative resection. While liver transplant has been the standard of care for unresectable hepatocellular carcinoma (HCC), its indications have expanded to other oncologic indications based on promising data from select centers. This review focuses on the utilization of liver transplant for HCC, cholangiocarcinoma, and colorectal liver metastasis.

In the realm of HCC, immunotherapy is an emerging treatment that has the potential for use in the advanced and neoadjuvant setting. It can benefit patients by downstaging them to resectable or transplantable disease burden. Regarding cholangiocarcinoma, better molecular profiling and targeted therapies have benefited patients, and ongoing studies in the United States and internationally will help further delineate the patients with cholangiocarcinoma who benefit from transplantation. Finally, there is emerging evidence that liver transplant for colorectal liver metastases can be safe and effective. While there is promising data showing survival benefit of liver transplantation (LT) for CRLM, standardized guidelines and recommendations in coordination with multidisciplinary oncology teams will be essential for establishing best practices.

Similar to the evolution of LT becoming the standard of care for well selected patients with HCC, the evolution of the role for LT for other hepatobiliary malignancies is quickly progressing as centers in Europe, Asia, and North America gain experience and develop protocols for selected patients with favorable tumor biology. Optimal oncology treatment requires multidisciplinary tumor board and case-by-case approaches which are essential for providing these patients with the best chance at optimal survival.

Hepatocellular carcinoma arises in the setting of cirrhosis in most cases, requiring multidisciplinary input to define resectability. In this regard, more precise surgical management considers patient factors and anatomical states, including resection margins, tumour biology, and perioperative therapy. Together with advances in surgical techniques, this integrated approach has resulted in considerable improvements in patient morbidity and oncological outcomes. Despite this, recurrence rates in hepatocellular carcinoma remain high. As the systemic treatment landscape in hepatocellular carcinoma continues to evolve and locoregional options are increasingly used, we review current and future opportunities to individualise the surgical management of patients with hepatocellular carcinoma.

Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct-acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash-out period before LT and post-LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non-hepatic complications must be understood to prevent them from becoming obstacles to long-term OS.

In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.

Transplant oncology integrates a wide variety of fields, such as surgery, oncology, and transplant medicine, intending to increase the range of studies and treatments for hepatobiliary cancers and other liver-related malignant lesions. Liver transplantation (LT) has proven to be an effective treatment for hepatocellular carcinoma. While the Milan criteria are still the gold standard, several new, more inclusive criteria have been proposed, and hepatocellular carcinoma has become a major indication for liver transplantation. The continuous evolution of diagnostic technologies supported this with higher image quality and more accurate staging. This review describes the current applications of transplant oncology in hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and liver metastatic disease from colorectal cancer and discusses the path that led to the development of transplant oncology as an organized approach to managing gastrointestinal malignancies through transplantation. More importantly, the significance of a multidisciplinary approach and criteria in the selection of suitable candidates are discussed. In addition, newer aspects of transplant oncology, such as immunotherapy, circulating tumor DNA (ctDNA), novel surgical techniques, and the utilization of artificial intelligence, are presented. Finally, the opportunities and challenges involved in the field's future, as well as the evolution of the criteria used over the years and insightful thoughts for the future of the criteria, are discussed.

To develop and validate an integrated model that combines CT-based radiomics and imaging biomarkers with clinical variables to predict recurrence and recurrence-free survival in patients with HCC following liver transplantation (LT), this 2-center retrospective study includes 123 patients with HCC who underwent LT between 2007 and 2021. Radiomic features (RFs) were extracted from baseline CT liver tumor volume. Feature selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method with 10-fold cross-validation in the training cohort (n=48) to build a predictive radiomics signature for HCC recurrence. Combined diagnostic models were built based on the radiomics signature supplemented with imaging features beyond the Milan criteria, the AFP (alpha-fetoprotein) model, and Metroticket 2.0 before LT using multivariate logistic regression. Receiver operating characteristic analyses were performed in both internal (n=22) and external (n=53) validation cohorts, and patients were stratified into either high-risk or low-risk groups for HCC recurrence. Kaplan-Meier analysis was performed to analyze recurrence-free survival. LASSO and multivariate regression analysis revealed 4 independent predictors associated with an increased risk of HCC recurrence: radiomics signature of 5 RF, peritumoral enhancement, satellite nodules, and no bridging therapies. For the prediction of tumor recurrence, the highest AUC of the final integrated models combining clinical variables, non-radiomics imaging features, and radiomics was 0.990 and 0.900 for the internal and external validation sets, respectively, outperforming the Milan and clinical stand-alone models. In all integrated models, the high-risk groups had a shorter recurrence-free survival than the corresponding low-risk group. CT-based radiomics and imaging parameters beyond the Milan criteria representing aggressive behavior, along with the history of bridging therapies, show potential for predicting HCC recurrence after LT.

Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.

Patients with hepatitis D virus (HDV)/hepatitis B virus (HBV)-related end-stage liver disease candidates for liver transplantation (LT) have traditionally been regarded as a special population, although their outcomes are controversial. An intention-to-treat (ITT) analysis of long-term outcomes of HDV/HBV-coinfected patients waitlisted for LT in Italy, between 2011 and 2020, was performed and compared with HBV-monoinfected LT candidates. Of 1731 HBV-infected LT candidates, 1237 (71.5%) had HBV monoinfection and 494 (28.5%) HDV/HBV coinfection. At listing, HDV/HBV-coinfected patients were significantly younger, listed mainly for decompensated cirrhosis, and with fewer hepatocellular carcinoma (HCC) cases; (26% vs 65.8%; P <.0001) compared with HBV-monoinfected patients. HDV/HBV-coinfected patients showed better 5-year ITT survival (83.2%; 95% CI: 79.4%-83.4%, vs 71.6%; 95% CI: 68.8%-74.2%; P < .0001). ITT-multivariable analysis identified the presence of HCC, advanced recipient age, and high model for end-stage liver disease-Na scores as mortality risk factors. Five years after LT, 99.1% of HDV/HBV-coinfected patients received oral nucleos(t)ide analogs, with immunoglobulins against antigen of the hepatitis B virus in 91.8% of cases. HBV and HDV viral recurrences were 1.1% and 0.2%, respectively, whereas recurrent or de novo HCC were 8.9% and 0.3%, respectively. In Italy, HDV/HBV-coinfected patients waitlisted for LT showed more favorable outcomes compared with HBV-monoinfected patients, both before and after LT. These excellent results, from the largest cohort reported so far, suggest that HDV/HBV-coinfected LT recipients do not represent a risky population and may be considered for simpler long-term antiviral prophylactic strategies.

This study was conducted to examine the dose-related effects over time of oleuropein on the proliferation and area of tumor spheroids in hepatocellular carcinoma cells.

We examined the possible effects of 100 to 500 μM dose concentrations of oleuropein on HepG2 cell proliferation using a real-time cell analyzer. A 3-dimensional hepatocellular carcinoma tumor spheroid model was established by seeding HepG2 cells at a density of 160 cells/well in custom 96-well microplates with low attachment surfaces and culturing for 3 days. Tumor spheres were treated with increasing oleuropein doses for 72 hours, and images were captured every 24 hours. The dose-dependent effects of oleuropein on tumor sphere size were analyzed by measuring the area of tumor spheres with ImageJ software. We conducted oleuropein viability and cytotoxicity analyses using calcein acetoxymethyl ester-based and propidium iodide-based staining in the tumor model.

Oleuropein inhibited cell proliferation; as the dose concentration of oleuropein increased, so did its capacity to inhibit cell proliferation (P < .001). The size of untreated tumor spheres increased at 72 hours (P < .001). However, treatment with 100 to 500 μM oleuropein reduced tumor size by 63.56% to 88.06% compared with untreated cells at the end of 72 hours (P < .001). With increasing concentrations, oleuropein inhibited the viability of tumor spheres, eliminating necrotic death caused by tumor hypoxia.

Overall, oleuropein reduced the size of tumors by inhibiting tumor proliferation and viability. In this context, oleuropein could be a candidate molecule for further extensive studies to reduce hepatocellular carcinoma tumors to meet Milan criteria for liver transplant.

Living donor liver transplantation (LDLT) offers timely curative treatment for unresectable hepatocellular carcinoma (HCC). This study aims to validate and compare previous prediction models for HCC outcomes in 488 LDLT recipients.

For 488 patients who underwent LDLT for HCC, pretransplant imaging studies assessed by modified RECSIT criteria, tumor markers such as alpha feto-protein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA II), and explant pathology were recruited. C-index of models for the HCC outcomes was compared, followed by further investigation for the predictive performances of the best model.

We found MoRAL (11√PIVKA-II + 2√AFP) demonstrated a higher C-index for HCC recurrence than other models that included radiologically viable tumor number and/or size (MoRAL: 0.709, Milan: 0.537, UCSF: 0.575, Up-to-7: 0.572, French AFP: 0.634, Pre-MORAL: 0.637, HALT-HCC: 0.626, Metroticket2.0: 0.629) and also had the highest C-index for HCC-specific deaths (0.706). Five-year HCC recurrence was well stratified upon dividing the patients into three groups by MoRAL cutoffs (11.9% for MoRAL < 100, 29.6% for MoRAL 100-200, and 48.6% for MoRAL > 200, p < 0.001). However, patients with major vessel invasion or portal vein tumor thrombus showed similarly high HCC recurrence regardless of this grouping (p = 0.612).

The MoRAL, based on tumor markers, showed the best predictive performance for HCC recurrence and HCC-specific death among the validated models, except in cases with major vessel invasion or portal vein tumor thrombus.

Liver transplantation is aptly described as the only curative treatment for cirrhosis and cirrhosis with co-morbid hepatocellular carcinoma (HCC). Its utility in the management of various other primary and secondary liver cancers is gaining traction rapidly, with more thorough assessments on broader populations continuing to emerge. Most prominently, this includes colorectal cancer liver metastasis (CRLM), cholangiocarcinoma (CCA), neuroendocrine tumors (NETs), and more. Furthermore, despite being a well described treatment for HCC for many years, growing evidence supports a change in oncological strategy for HCC, with broadened selection criteria and more advanced systemic and locoregional therapies available. Our review aims to describe the evidence supporting the expansion of indications and selection criteria for liver transplantation in various oncologic indications of primary and secondary liver tumors.

Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, characterized by a high rate of recurrence. This study aims to compare the efficacy and safety of repeat hepatectomy (RH) and salvage liver transplantation (sLT) for recurrent hepatocellular carcinoma (rHCC) and explores the predictive value of neutrophil-to-lymphocyte ratio (NLR) and neutrophil extracellular traps (NETs).

In this study, consecutive patients receiving RH (n = 637) or sLT (n = 53) for rHCC within the University of California San Francisco (UCSF) Criteria were recruited. After propensity score matching (PSM), disease-free survival (DFS) and overall survival (OS) were compared utilizing the Kaplan-Meier method. Additionally, the level of neutrophil infiltration and NETs were analyzed by multiplex immunofluorescence.

After PSM, the sLT group demonstrated superior 5-year DFS and OS compared to the RH group (p < 0.001 and p = 0.014). Subgroup analysis demonstrated that NLR > 2.3 was associated with poorer OS (p < 0.001 in the RH group and p = 0.024 in the sLT group) and DFS (p = 0.002 in both groups). Furthermore, we identified that patients in the sLT group are more susceptible to extrahepatic metastasis. In addition, our results revealed that higher infiltration of intratumoral neutrophils was negatively correlated with OS and DFS (p = 0.002 and p = 0.001, respectively), especially in cases with higher NETs level.

This study indicates that sLT achieves better long-term outcomes than RH for rHCC. NLR and NETs formation are promising prognostic factors for HCC.

Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.

Background/Objectives: Since their introduction in the 1990s, the Milan criteria have been the gold standard of indication for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Nevertheless, several institutions have reported wider indication criteria for LT with comparable survival outcomes. Methods: This paper summarizes the recent indications for LT for HCC through a literature review. Results: There are several criteria expanding the Milan criteria, which can be subdivided into the "based on tumor number and size only", "based on tumor number and size plus tumor markers", and "based on tumor differentiation" groups, with the outcomes being comparable to those of patients included within the Milan criteria. Besides the tumor size and number, which are included in the Milan criteria, recent criteria included biomarkers and tumor differentiation. Several retrospective studies have reported microvascular invasion (MVI) as a significant risk factor for postoperative recurrence, highlighting the importance of preoperatively predicting MVI. Several studies attempted to identify preoperative predictive factors for MVI using tumor markers or preoperative imaging findings. Patients with HCC who are LT candidates are often treated while on the waiting list to prevent the progression of HCC or to reduce the measurable disease burden of HCC. The expanding repertoire of chemotherapeutic regiments suitable for patients with HCC should be further investigated. Conclusions: There are several criteria expanding Milan criteria, with the outcomes being comparable to those of patients included within the Milan criteria.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths rising worldwide. This is leading to an increased demand for liver transplantation (LT), the most effective treatment for HCC in its initial stages. However, current patient selection criteria are limited in predicting recurrence and raise ethical concerns about equitable access to care. This study aims to enhance patient selection by refining the HepatoPredict (HP) tool, a machine learning-based model that combines molecular and clinical data to forecast LT outcomes.

The updated HP algorithm was trained on a two-center dataset and assessed against standard clinical criteria. Its prognostic performance was evaluated through accuracy metrics, with additional analyses considering tumor heterogeneity and potential sampling bias.

HP outperformed all clinical criteria, particularly regarding negative predictive value, addressing critical limitations in existing selection strategies. It also demonstrated improved differentiation of recurrence-free and overall survival outcomes. Importantly, the prognostic accuracy of HP remained largely unaffected by intra-nodule and intra-patient heterogeneity, indicating its robustness even when biopsies were taken from smaller or non-dominant nodules.

These findings support the usage of HP as a valuable tool for optimizing LT candidate selection, promoting fair organ allocation and enhancing patient outcomes through integrated analysis of molecular and clinical data.

Hepatocellular carcinoma (HCC) persists as a leading cause of cancer-related mortality, often diagnosed at advanced stages with limited treatment options. Locoregional therapies (LRTs) are crucial in HCC management, playing significant roles in neoadjuvant and palliative treatments, among others. However, the unique disease background of HCC necessitates multidisciplinary and integrated treatment strategies. The therapeutic landscape for advanced HCC has been significantly broadened by the advent of combined therapies, presenting multiple approaches aimed at improving long-term survival, which remains a critical challenge. This review offers a comprehensive overview of major LRTs for HCC, highlighting recent technological advancements and exploring the challenges and limitations in their application, and presents the latest developments in combination therapies, including combinations between different LRTs and their integration with systemic treatments. Additionally, we outline future directions for the development of integrated treatment modalities for advanced HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.