Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced‐stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post‐surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced‐stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

Distant metastasis after hepatectomy for hepatocellular carcinoma (HCC) significantly impairs long-term outcome. This study aimed to identify patterns, risk factors, and develop a prediction model for distant metastasis at first recurrence following HCC resection. This multi-center retrospective study included patients undergoing curative hepatectomy for HCC. Risk factors for distant metastasis were identified using Cox regression. A nomogram was constructed and validated using the concordance index (C-index) and calibration curves. Among 2,705 patients, 1,507 experienced recurrence, with 342 (22.7 per cent) developing distant metastasis. Common metastatic sites included extrahepatic vessels (36.2 per cent), lungs (26.0 per cent), and lymph nodes (20.8 per cent). Patients with distant metastasis had significantly worse 5-year overall survival compared to those with intrahepatic recurrence (9.1 versus 41.1 per cent, p < 0.001). Independent risk factors included preoperative tumor rupture, tumor size over 5.0 cm, multiple tumors, satellite nodules, macro- and microvascular invasion, narrow resection margin, and intraoperative blood transfusion. The nomogram demonstrated excellent discrimination (C-index > 0.85) and accurately stratified patients into three risk categories. In conclusion, distant metastasis at first recurrence following HCC resection was associated with poor prognosis. The proposed nomogram facilitates accurate prediction of distant metastasis, potentially informing personalized postoperative monitoring and interventions for high-risk patients.

Hepatocellular carcinoma (HCC) is a highly lethal and heterogeneous malignancy with multiple genetic alternations and complex signaling pathways. The complexity and multifactorial nature of HCC pose a tremendous challenge regarding its diagnosis and treatment. Emerging evidence has indicated an important regulatory role of epigenetic modifications in HCC initiation and progression. Epigenetic modifications are stably heritable gene expression traits caused by changing the accessibility of chromatin structure and genetic activity without alteration in the DNA sequence and have been gradually recognized as a hallmark of cancer. In addition, accumulating data suggest a potential value of altered hydroxymethylation in epigenetic modifications and therapeutics targeting the epigenetically mediated regulation. As such, probing the epigenetic field in the era of precision oncology is a valid avenue for promoting the accuracy of early diagnosis and improving the oncological prognosis of HCC patients. This review focuses on the diagnostic performance and clinical utility of 5-hydroxymethylated cytosine, the primary intermediate product of the demethylation process, for early HCC diagnosis and discusses the promising applications of epigenetic-based therapeutic regimens for HCC.

Hepatocellular carcinoma (HCC) remains a major global health burden characterized by late-stage diagnosis and high postoperative recurrence rates. This review presents a surgery-centered precision management framework integrating 3 synergistic components: early detection, precision surgery, and recurrence prevention. Early detection strategies incorporate multiparameter risk models including the gender, age, AFP-L3, AFP, and DCP (GALAD) as well as age, sex, AFP, and PIVKA-II (ASAP) scores, alongside circulating tumor DNA methylation-based liquid biopsy, thus enabling tumor identification at stages amenable to curative resection. Precision surgery optimizes patient selection through refined staging systems including the Chinese liver cancer staging (CNLC), and functional assessments including the albumin–bilirubin (ALBI) grade, whereas conversion therapy and minimally invasive approaches extend surgical eligibility to selected patients with intermediate-stage disease. To mitigate the risk of postoperative recurrence, distinguishing between early and late recurrence patterns and monitoring minimal residual disease are critical strategies. Perioperative systemic therapies, particularly immune checkpoint inhibitor-based combinations, show promise for eradicating micrometastatic disease. This integrated framework provides a cohesive, evidence-based approach to personalized HCC management aimed at maximizing curative potential and long-term survival.