Immune checkpoint inhibitor (ICI)-based combination therapy has transformed the treatment of advanced hepatocellular carcinoma (HCC), yet immune-related adverse events (irAEs) remain a serious and potentially fatal complication. We report two cases of severe irAEs following ICIbased therapy for HCC. In Case 1, a man with multimetastatic HCC developed immune-mediated colitis with hemodynamic collapse and multi-organ failure after the second cycle of the STRIDE regimen yet achieved a near-complete oncologic response. In Case 2, a patient who had tolerated 17 cycles of adjuvant atezolizumab (ate) plus bevacizumab (bev) without irAE developed fatal immune-mediated fulminant hepatitis after a single dose of ate+bev reinitiated as first-line therapy for unresectable HCC following recurrence and TACE failure. These cases highlight the unpredictability of irAEs—even in previously tolerant patients—and underscore the importance of early recognition and prompt management.

Hepatic angiomyolipoma (HAML) is a rare mesenchymal tumor of the liver composed of varying proportions of adipose tissue, smooth muscle cells, and blood vessels. Its heterogenous composition results in diverse features that may closely mimic hepatocellular carcinoma (HCC) on imaging. Here, we report a 56-year-old woman was referred after an incidental 1.8 cm hepatic mass on computed tomography. Magnetic resonance imaging demonstrated arterial phase hyperenhancement, portal venous washout, hepatobiliary phase hypointensity, and diffusion restriction, strongly mimicking the imaging appearance of HCC. However, the absence of chronic liver disease or viral hepatitis limited a confident noninvasive diagnosis. To establish a definitive diagnosis, percutaneous tumor biopsy was performed. Histologically, the lesion consisted showed a characteristic admixture of smooth muscle cells, adipose tissue, and blood vessels, and immunohistochemistry demonstrated diffuse positivity for HMB-45, confirming the diagnosis of HAML.

Hepatocellular carcinoma (HCC) is a highly lethal cancer in which epigenetic dysregulation plays a key role in tumor development and progression. Among epigenetic mechanisms, histone methylation regulates chromatin structure and gene transcription and influences multiple aspects of HCC biology, including tumor proliferation, metastasis, immune modulation, cancer stemness, and therapeutic resistance. In this review, we summarize recent advances in understanding the roles of histone methyltransferases in HCC, focusing on their involvement in tumor proliferation, metastasis, immune regulation, drug resistance, and cancer stem cell maintenance. We also discuss their clinical relevance as potential diagnostic and prognostic biomarkers and highlight emerging therapeutic strategies targeting histone methylation pathways. Collectively, these findings suggest that histone methyltransferases represent promising targets for developing novel epigenetic-based diagnostic and therapeutic approaches for HCC.

Radiotherapy has long been investigated as a therapeutic modality in the management of hepatocellular carcinoma (HCC). Recently, updated clinical frameworks in the Barcelona Clinic Liver Cancer guidelines have allowed greater flexibility in integrating radiotherapy across disease stages. This review synthesizes contemporary prospective studies and systematic reviews/meta-analyses published over the past five years to clarify the current and emerging clinical roles of radiotherapy in real-world HCC management. Recent evidence highlights expanding applications of radiotherapy, including curative-intent stereotactic body radiotherapy in early-stage disease, consolidation after incomplete transarterial chemoembolization, perioperative strategies, and treatment of macroscopic vascular invasion. Radiotherapy is increasingly integrated with tyrosine kinase inhibitors and immune checkpoint inhibitors in advanced, oligometastatic, and oligoprogressive settings. In addition, particle therapies further broaden therapeutic options for liver-confined or anatomically challenging tumors. Collectively, contemporary data indicate that radiotherapy has evolved from a predominantly supportive modality to a versatile and increasingly evidence-based component of multidisciplinary treatment strategies for HCC.

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.

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.

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.

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.

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.