Soon Sun Kim, Hyun Yang, Jieun Kwon, Eunju Kim, Jeong Il Yu, Janghan Jung, Woosun Choi, Ji Eun Han, Moon Haeng Hur, Bo Hyun Kim, Sung Hyun Kim, Jeong Han Kim, Haeryoung Kim, Pyoung-Jae Park, Hyun Phil Shin, Su Jong Yu, Ki Tae Yoon, Sang Min Yoon, Minjong Lee, Jai Young Cho, Jin-Young Choi, Do Young Kim, June Sung Lee, Mi-Sook Kim, Kyung Sik Kim
J Liver Cancer. 2025;25(2):169-177. Published online September 2, 2025
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.
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.
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.
Hyun Yang, Soon Sun Kim, Seong Hee Kang, Jieun Kwon, Do Young Kim, Eunju Kim, Hyun Phil Shin, Jeong Il Yu, Jeong-Ju Yoo, Eileen L. Yoon, Sangheun Lee, Young Eun Chon, Janghan Jung, Jaekyung Cheon, Woosun Choi, Seul Ki Han, Ji Eun Han, Moon Haeng Hur, Hyun Woong Lee, Hyung Joon Kim
J Liver Cancer. 2025;25(2):160-168. Published online July 7, 2025
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.
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.
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.
Backgrounds/Aims In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. CSCs are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy.
Methods CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns.
Results Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in CD133- or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and quantitative polymerase chain reaction (qPCR).
Conclusion The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.
Hepatocellular carcinoma (HCC) presents unique challenges in both the elderly and adolescent/young adult (AYA) populations, requiring distinct management approaches. Recent epidemiological data show an increasing incidence of HCC in both age groups, with elderly cases rising significantly and AYA cases showing trends in specific regions. The clinical characteristics and treatment considerations vary substantially among these populations. Elderly patients with HCC typically present with hepatitis C virus infection, metabolic dysfunction-associated steatotic liver disease, well-differentiated tumors, and multiple comorbidities. In contrast, AYA patients with HCC often present with more aggressive tumor characteristics and predominantly with hepatitis B virus-related diseases. Treatment decisions for elderly patients with HCC require careful consideration of physiological reserves, comprehensive geriatric assessments, and potential complications. Recent studies have demonstrated that elderly patients can achieve outcomes comparable to younger patients across various treatment modalities when properly selected. While surgical outcomes are comparable to those of younger patients with proper selection, less-invasive options such as radiofrequency ablation or transarterial therapies may be more appropriate for some elderly patients. The treatment approach for AYA HCC emphasizes curative intent while considering long-term effects. AYA patients require specialized attention to their psychosocial needs, fertility preservation, and long-term health maintenance. Although data on AYA patients remain limited, they are known to have relatively favorable prognoses despite exhibiting more aggressive tumor characteristics. Management of HCC in both the elderly and AYA populations requires individualized approaches that consider age-specific factors. Both groups benefit from multidisciplinary team involvement and careful consideration of quality of life.
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Backgrounds/Aims Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018.
Methods Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018.
Results The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%).
Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.
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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Early detection via surveillance plays a crucial role in enabling curative treatment and improving survival rates. Since the initial randomized controlled trial, biannual ultrasound (US) has been established as the standard surveillance method because of its accessibility, safety, and low cost. However, US has some limitations, including operator dependency, suboptimal sensitivity for early-stage HCC, and challenges such as a limited sonic window that may result in inadequate examination. Alternative imaging modalities, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), have demonstrated higher sensitivity for detecting very early-stage HCC. Recent advancements, such as low-dose CT with deep learning-based reconstruction, have enhanced the safety and feasibility of CT-based surveillance by reducing radiation exposure and amount of contrast media. MRI, particularly with gadoxetic acid or abbreviated protocols, offers superior tissue contrast and sensitivity, although its accessibility and cost remain challenges. Tailored surveillance strategies based on individual risk profiles and integration of advanced imaging technologies have the potential to enhance the detection performance and cost-effectiveness. This review highlights the recent developments in imaging technologies for HCC surveillance, focusing on their respective strengths and limitations.
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Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.
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Backgrounds/Aims Microwave ablation (MWA) is an emerging ablative therapy that surpasses previous methods by achieving higher temperatures and creating larger ablation zones within shorter periods. This study compared the therapeutic outcomes of MWA with those of liver resection in real-world clinical practice.
Methods A total of 178 patients with 259 nodules who underwent MWA or liver resection between January 2015 and July 2023 were enrolled. Local tumor progression (LTP)-free survival, overall progression (OP)-free survival, and overall survival (OS) were assessed based on the treatment modality for the index nodule.
Results Of the 178 patients, 134 with 214 nodules underwent MWA, and 44 with 45 nodules underwent liver resection. The median follow-up period was 2.0±1.5 years. The annual incidence of LTP was 3.7% for MWA and 1.4% for liver resection. Treatment modality did not significantly affect LTP-free survival (hazard ratio, 0.61; 95% confidence interval, 0.14-2.69; P=0.511). For nodules larger than 3 cm, LTP-free survival was not affected by the treatment modality. Similarly, OP-free survival and OS were not influenced by treatment modality.
Conclusions MWA and liver resection demonstrated comparable treatment outcomes in terms of local tumor control, overall recurrence, and survival. MWA may be an alternative treatment option for select patients; however, further studies are necessary to generalize these findings.
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Backgrounds/Aims Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE.
Methods Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP.
Results The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively.
Conclusions Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.
Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a dismal prognosis. Atezolizumab plus bevacizumab (atezo-bev) is the recommended palliative treatment, and approximately 10% of the patients may experience a complete response (CR), according to the mRECIST criteria. The treatment duration is until disease progression or unacceptable side effects occur. Long-term continuation can cause potential toxicities and a substantial financial burden, making early treatment discontinuation a viable option. This report describes durable CR after discontinuing atezo-bev treatment in three patients with HCC and PVTT.