Recently, the survival benefit of immuno-oncologic (IO) agents for advanced hepatocellular carcinoma (HCC) has been proven in several randomized controlled trials. Especially, atezolizumab with bevacizumab (Ate+Beva), as a first-line therapy for advanced HCC, has shown outstanding efficacy in the IMBrave150 study. Fortunately in south Korea, the cost of Ate+Beva therapy can be covered by national medical insurance, therefore HCC patients can receive Ate+Beva therapy without trouble. However, almost all HCC patients have no choice but to stop the treatment after two years completion of Ate+Beva therapy because our national medical insurance only cover IO therapy for two years. Therefore clinicians have been restarting the systemic treatment after confirming the disease progression of HCC patients on resting period of systemic therapy. Here, we report a case that showed a partial response of lymph node metastasis by 3rd line regorafenib therapy for progression of LN metastasis after achieving nearly complete response by two-year completion of 1st line Ate+Beva therapy in advanced HCC patient.

Immune checkpoint inhibitors (ICIs) have robust therapeutic efficacy, offering sustained clinical benefit in various malignancies. However, the optimal duration of treatment remains under investigation. This review summarizes recent trends in long-term ICI therapy, with particular focus on hepatocellular carcinoma (HCC). The conventional 2-year treatment limitation, initially based on data from non-small cell lung cancer trials (e.g., KEYNOTE-010, Check-Mate-017), has been adopted broadly across tumor types. Follow-up data suggest that many patients maintain remission even after discontinuation of treatment, prompting reevaluation of prolonged therapy necessity. In HCC, atezolizumab plus bevacizumab has become the firstline standard treatment, but questions persist regarding continuation beyond two years and post-progression management. Emerging data indicate that salvage therapies—including tyrosine kinase inhibitors like sorafenib or lenvatinib—remain viable options after ICI failure. Furthermore, recent studies from European cohorts and Asian populations have provided insights into long-term survival, treatment sequencing. This review aims to provide a clinical and practical overview of these evolving paradigms to guide personalized, evidence-based decisions in immune-oncology.

Liver transplantation (LT) is a curative therapy for selected patients with hepatocellular carcinoma (HCC) and cirrhosis, simultaneously treating tumors and underlying liver disease. This review provides an up-to-date overview of LT for HCC, focusing on key considerations for hepatobiliary surgeons. We discuss established selection criteria (Milan and University of California, San Francisco) and the evolution of expanded eligibility models incorporating tumor biology (e.g., “up-to-7” criteria, alpha-fetoprotein–based models). Outcomes of LT for HCC are excellent in appropriately selected patients, with 5-year survival >70% and low recurrence rates when within criteria. We examine strategies for downstaging advanced HCC to transplantable disease, which have enabled curative LT in patients initially beyond criteria with acceptable 10-year outcomes. We compare living donor and deceased donor LT, highlighting the role of living donor transplantation in expanding access and its comparable survival. Immunosuppression protocols are reviewed, with an emphasis on striking a balance between preventing rejection and minimizing the risk of tumor recurrence. We also address global trends and challenges, including organ shortages and ethical considerations, and survey recent innovations from clinical trials and translational research—such as machine perfusion organ preservation, novel biomarkers, and immunotherapy—for their potential impact on HCC transplant practice.

Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related mortality worldwide, largely because of its late detection and high recurrence rates. Conventional biomarkers such as alpha-fetoprotein (AFP) are unable to detect early-stage diseases with sufficient accuracy. Exosomal microRNAs (miRNAs) are small non-coding RNAs, encapsulated within extracellular vesicles, that have emerged as highly sensitive and specific non-invasive biomarkers with revolutionary potentials for improving HCC diagnosis and prognosis prediction. Several studies have demonstrated that circulating exosomal miRNAs outperform AFP detection in differentiating early-stage HCC from chronic liver disease and in predicting metastasis, recurrence, and patient survival. Furthermore, multi-miRNA panels and AI-driven predictive models integrating exosomal miRNA signatures with clinical parameters enhance the diagnostic accuracy and enable personalized risk stratification. Despite promising results, clinical implementation has been challenged by assay standardization, interpatient variability, and the need for large-scale prospective validation. Future research should include developing robust, high-throughput exosomal miRNA detection platforms, incorporating machine learning for optimized biomarker selection, and integrating exosomal miRNAs with other liquid biopsy approaches for comprehensive disease monitoring. In summary, exosomal miRNAs represent a powerful tool for revolutionizing the early detection and tailored management of HCC, ultimately improving patient outcomes through timely and precise interventions.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and therapeutic cancer vaccines have emerged as a promising immunotherapeutic strategy. These vaccines target tumor-associated antigens such as glypican-3, alpha-fetoprotein, melanoma-associate antigen-1, heat shock protein 70, glutamine synthetase, and TMEM176A/B, which are abnormally expressed in HCC cells and serve as both diagnostic markers and therapeutic targets. Various vaccine platforms—including peptide-based, dendritic cells-based, viral vector-based, and genetic vaccines (DNA/mRNA)—are under investigation for their ability to elicit antigen-specific cytotoxic T cell responses and establish long-term immune memory. Despite promising preclinical and early clinical results, challenges such as the immunosuppressive tumor microenvironment, antigen heterogeneity, and immune evasion mechanisms limit their efficacy. Future strategies focus on combination therapies with immune checkpoint inhibitors, personalized neoantigen vaccines, and advanced delivery technologies. These approaches aim to enhance immunogenicity and clinical outcomes, positioning therapeutic cancer vaccines as a key component of precision oncology in HCC.