Journal of liver cancer最新文献

Surgical resection for early-stage hepatocellular carcinoma (HCC) provides the potential for long-term survival but recurrence rates within 5 years were up to 70%. Thus, neoadjuvant or adjuvant strategies can be important to improve outcomes. Previous efforts with sorafenib in the adjuvant setting failed to show significant benefits in recurrence-free survival (RFS) or overall survival. However, developments in systemic therapies such as immune checkpoint inhibitors or tyrosine kinase inhibitors have revitalized this field. Although the IMBrave050 trial failed to demonstrate a significant improvement in RFS with one year of adjuvant treatment using atezolizumab combined with bevacizumab in high-risk patients treated with resection or ablation, several other ongoing trials are investigating this promising approach. Neoadjuvant or adjuvant approach using systemic therapies is also gaining attention, supported by phase 1 or 2 clinical trials indicating high objective response rates. In addition, systemic therapies are being increasingly studied as down-staging strategies for resection or liver transplantation. The growing complexity of HCC treatment such as the integration of neoadjuvant and adjuvant strategies underscores the importance of a multidisciplinary approach to optimize therapeutic decision-making in this evolving areas.

The use of laparoscopic liver resection has rapidly increased. According to two international consensus meetings, certain resection methods are already considered standard procedures for liver resection, especially for small malignant tumors located on the liver surface or in the anterolateral segments of the liver. However, further studies and international consensus meetings are required for laparoscopic procedures to be accepted as standard procedures for highly complex hepatectomies, major hepatectomies, anatomical resections, and laparoscopic donor hepatectomies. Technical refinements are necessary because many studies have shown that negative outcomes also affect long-term outcomes after laparoscopic liver resection for hepatocellular carcinoma.

This survey aimed to collect expert opinions from multidisciplinary specialists involved in the management of hepatocellular carcinoma (HCC) in Korea regarding real-world criteria for systemic therapy indications. In response to discrepancies between national reimbursement policies and clinical decision-making, members of the Korean Liver Cancer Association and Korean Association for the Study of the Liver participated in a web-based survey from February 4 to 14, 2025. A total of 89 respondents, primarily experienced clinicians, provided their views on major clinical scenarios including infiltrative HCC, bilobar multifocal disease, huge tumors, vascular invasion, extrahepatic metastasis, and transarterial chemoembolization (TACE) refractoriness. There was high agreement for including infiltrative HCC (69.7%), suspected portal vein invasion (70.8%), and TACE refractoriness (82.0%) as systemic therapy indications. TACE refractoriness, in particular, aligns with current guideline definitions. Additionally, over half of respondents (51.7%) supported extrahepatic metastasis under similar conditions. Notably, multidisciplinary discussion was emphasized across scenarios, but many respondents also favored allowing primary physician discretion in select cases. This report provides consolidated expert input to inform future updates to reimbursement policies and promote alignment with real-world clinical practice. These findings may help bridge the gap between national coverage criteria and clinical decision in systemic therapy for HCC.

Backgrounds/aims: Identifying metabolic biomarkers can enhance early detection and risk stratification of hepatocellular carcinoma (HCC). We conducted a two-sample Mendelian randomization (MR) study to assess the potential causal effects of metabolites on HCC risk.

Methods: We performed meta-analyses to pool the effects of genetic instruments from 64 previously published genome-wide association studies. Summary statistics for HCC were obtained from a meta-analysis of the UK BioBank and FinnGen cohorts. MR analyses for the association between 3,275 metabolites and HCC risk were performed using inverse variance weighted, weighted median, MR-Egger, and MR-PRESSO methods to estimate the association. Enrichment analyses were performed on the significant metabolites to identify biological pathways associated with macronutrient intake.

Results: We identified 99 metabolites that were positively and 36 metabolites that were negatively associated with HCC risk. Methyl glucopyranoside and phosphatidylcholine C38:3 were positively associated with HCC risk, whereas while 3-dehydrocarnitine and 10-undecenoate were inversely associated, with no evidence of heterogeneity, pleiotropy, or outlier effects for any of these associations. Pathway enrichment analysis showed that metabolites associated with increased HCC risk were primarily related to amino acid transport and solute carrier transporter disorders, whereas those linked to reduced risk were mainly involved in inositol and phosphatidylinositol metabolism, glycerophospholipid catabolism, and MeCP2-related regulatory processes.

Conclusions: This comprehensive MR study identified several metabolites with potential causal roles in HCC development. Our findings highlight nutrient transport, lipid metabolism, and related regulatory mechanisms as key components of HCC pathogenesis, offering new avenues for biomarker discovery and therapeutic intervention.

Hepatocellular carcinoma (HCC) is the most prevalent primary hepatic malignancy and is globally the third leading cause of cancerrelated deaths. Despite significant advancements in diagnostic techniques and therapeutic interventions, HCC prognosis remains poor due to asymptomatic progression, frequent recurrence, and inadequate treatment responsiveness. The development of HCC is closely linked to chronic liver diseases, such as hepatitis B and C infections, alcoholic liver disease, and metabolic dysfunctionassociated steatotic liver disease (MASLD). To better understand hepatocarcinogenesis and support therapeutic development, a range of animal models have been established. Among these animal models, mice are extensively utilized because of their genetic manipulability, physiological resemblance to humans, and relatively short experimental timelines. The most well-established protocol for analyzing the onset and progression of HCC is the diethylnitrosamine (DEN)-induced HCC model. Additionally, carbon tetrachloride (CCl4)-induced HCC models, DEN+CCl4 combination HCC models, MASLD HCC mouse models (STAMTM), alcoholassociated HCC models, hydrodynamics-based transfection systems, and orthotopic HCC transplantation approaches also provide distinct advantages for exploring specific elements of HCC pathophysiology. Unfortunately, due to the complexity and heterogeneity of human HCC, no single animal model can accurately recapitulate the disease. Therefore, careful selection or combination of appropriate mouse models for specific research objectives is crucial to enhance the translational value of preclinical studies. This review provides a comprehensive overview of the mouse models currently employed in HCC research, highlighting their respective strengths and limitations. Such understanding and application of these HCC models are essential for advancing mechanistic insights and fostering the development of novel therapeutic strategies.

In 2024, a nationwide conflict between the South Korean government and the medical community, the medical-policy conflict, profoundly impacted healthcare delivery. This study aimed to evaluate the changes in the management of hepatocellular carcinoma (HCC) following this crisis. We analyzed retrospective real-world data from university hospitals in the Seoul Metropolitan Area, supplemented with national healthcare data from the Health Insurance Review and Assessment Service. The analytical variables included changes in workforce composition, initial treatment modalities, HCC stage distribution, quality indicators for HCC care, regional and institutional variations in care delivery, and liver transplantation (LT) volume. A comparison between 2023 and 2024 revealed a marked decline in the number of medical trainees, a rise in the proportion of physician assistants, a 28.9% reduction in newly initiated HCC treatments, and an increased rate of stage IV diagnoses. Several quality indicators, including rates of multidisciplinary care and patient education, declined. The volume of LTs decreased by approximately 20% nationwide, with some regions ceasing LT procedures. The results suggest that serious disruptions occurred in HCC care following the conflict. The significant decrease in initial treatment and number of LT procedures, more advanced stages at diagnosis, and declining quality metrics indicate the emergence of healthcare gaps. Without the recovery of the clinical workforce and the reestablishment of a stable healthcare delivery system, the management of serious diseases such as HCC will remain structurally vulnerable. National-level efforts are urgently required to address regional disparities and restore essential medical services.

Diabetes mellitus is a cardiometabolic risk factor associated with the development of various comorbidities and malignancies. It has a bidirectional relationship with chronic liver disease, promoting hepatic inflammation and fibrosis, which can ultimately progress to advanced liver diseases such as cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Therefore, the importance of antidiabetic treatment has been increasingly emphasized as a strategy for preventing liver-related diseases in diabetic patients. Metformin, a first-line antidiabetic agent, has been shown to be effective in improving hepatic steatosis and preventing progression to advanced liver disease. Recently updated international guidelines recommend the use of metformin as a chemopreventive agent for HCC in diabetic patients, albeit with a weak recommendation. Meanwhile, as metformin alone is often insufficient for blood glucose control and concurrent metabolic comorbidities are increasingly prevalent, new second-line antidiabetic agents have been developed: glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors. These novel antidiabetic agents have demonstrated cardiovascular benefits, and protective effects on liver-related outcomes and mortality in previous studies. However, due to the limited number of studies and the variability in study populations, their effects remain inconsistent across different studies. Furthermore, there are no established therapeutic guidelines for diabetic patients with liver disease. Therefore, this review aims to examine the association between the use of novel second-line antidiabetic agents and the risk of liver-related outcomes and mortality in this population.

Orbital metastasis from hepatocellular carcinoma (HCC) is extremely rare, and patients often present with ocular symptoms before the primary tumor is diagnosed. Here, we report two cases of orbital metastasis from HCC with distinct clinical courses. The first case involved a patient with no prior cancer history who presented with vision loss and was subsequently diagnosed with HCC following an orbital mass biopsy. The second case involved a patient with known HCC undergoing treatment who initially presented with periorbital swelling misdiagnosed as cellulitis before orbital metastasis was confirmed. Both cases highlight the importance of considering orbital metastasis in patients with ocular symptoms, even in the absence of a known malignancy. Given the poor prognosis and limited treatment options for orbital metastasis, early recognition through imaging and histopathological confirmation is crucial for appropriate management.

Noninvasive imaging-based diagnosis of hepatocellular carcinoma (HCC) in high-risk patients plays a central role in clinical practice. Current major guidelines typically rely on the radiologic hallmark of nonrim arterial phase hyperenhancement followed by nonperipheral washout, criteria designed to achieve both high positive predictive value and sufficient specificity when applied within well-defined target populations. Despite these criteria, false positive diagnoses still occur and can lead to unnecessary or inappropriate treatment, as various benign and non-HCC malignant lesions may exhibit vascular features that overlap with the classic appearance of HCC. Furthermore, treatment decisions are occasionally guided by imaging findings even in patients outside the target population who are being evaluated for possible HCC, in whom vascular patterns are less specific and the risk of false positive diagnosis is inherently higher. Minimizing the risk of false positive diagnosis requires not only adherence to validated imaging criteria but also clinical and contextual integration when findings are uncertain. This includes consideration of ancillary features, tumor markers, and, when appropriate, further evaluation through biopsy, additional imaging, or follow-up. This review outlines a range of HCC mimickers and provides practical strategies to support accurate imaging interpretation and reduce false positive diagnoses in clinical practice.

Hepatocellular carcinoma (HCC) remains a major global health burden, ranking as one of the leading causes of cancer-related deaths worldwide. This review synthesizes current evidence on HCC epidemiology, highlighting both modifiable and non-modifiable risk factors, including chronic hepatitis B and C virus infections, metabolic dysfunction-associated steatotic liver disease (MASLD), excessive alcohol consumption, aflatoxin exposure, and genetic susceptibility. These diverse etiologies reflect not only biological mechanisms but also broader social and environmental determinants of health, emphasizing the need for integrated, population-level preventive strategies. Effective strategies across all levels of prevention are reviewed. Primordial and primary prevention strategies include public health policies, health education to raise awareness, universal hepatitis B vaccination, expanded access to antiviral therapies for hepatitis B virus (HBV) and hepatitis C virus (HCV), lifestyle interventions targeting obesity and alcohol use, and environmental controls to reduce aflatoxin exposure. Secondary prevention focuses on early detection through viral hepatitis screening and routine HCC surveillance in high-risk populations. Tertiary prevention aims to reduce morbidity and mortality through timely treatment and multidisciplinary care. Despite the availability of effective tools, substantial implementation gaps remain persist. Underdiagnosis of viral hepatitis, low treatment uptake, inadequate surveillance coverage, and disparities in healthcare access continue to limit progress. Addressing these challenges requires a coordinated public health response grounded in health system strengthening, policy innovation, and equitable access to care. A renewed public health commitment -integrating prevention, early diagnosis, and continuity of care- is essential to reduce the global burden of HCC and bridge the gap between knowledge and action.