Liver Cancer最新文献

{"title":"Liver Stiffness Measured by Vibration-Controlled Transient Elastography Predicts Hepatic Decompensation in Patients with Hepatocellular Carcinoma Receiving Systemic Treatments.","authors":"Jaejun Lee, Hyun Yang, Si Hyun Bae, Hee Sun Cho, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Keungmo Yang, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, Do Seon Song, Seok Hwan Kim, Myung Jun Song, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Ji Won Han","doi":"10.1159/000550440","DOIUrl":"10.1159/000550440","url":null,"abstract":"<p><strong>Background/aims: </strong>Hepatic decompensation (HD) following systemic treatment, including atezolizumab + bevacizumab (Atezo/Bev) and tyrosine kinase inhibitors (TKIs), is a critical prognostic event in advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the predictive utility of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) for HD incidence post-treatment.</p><p><strong>Methods: </strong>This multicenter study included 396 HCC patients who received systemic therapy (Atezo/Bev or TKIs) and underwent VCTE prior to treatment at seven university-affiliated hospitals. Clinical outcomes including HD independent of tumor progression, variceal bleeding (VB), overall survival (OS), and progression-free survival (PFS) were assessed. A 25 kPa LSM threshold, based on Baveno VII criteria, stratified patients into high and low LSM groups.</p><p><strong>Results: </strong>Of the 396 patients, 176 received Atezo/Bev, while 45 and 175 received lenvatinib and sorafenib, respectively. Treatment distribution was similar between high and low LSM groups (<i>p</i> = 0.546). High LSM was associated with increased HD risk (HR = 3.00, <i>p</i> < 0.001), VB risk (HR = 2.34, <i>p</i> = 0.048), and a trend toward worse OS (HR = 1.27, <i>p</i> = 0.065). In the low LSM group, Atezo/Bev outperformed TKIs in OS and PFS (<i>p</i> < 0.05) without increasing HD risk. In contrast, in the high LSM group, Atezo/Bev and TKIs showed no OS or PFS differences, but Atezo/Bev significantly increased HD and VB risk (<i>p</i> < 0.05). A risk score based on four variables (Child-Pugh score 5, LSM ≥25 kPa, multiple tumors, and high-grade portal vein tumor thrombosis) showed good predictive accuracy for HD at 12 months (AUC = 0.832) and effectively identified patients at high risk for HD, VB, and poor survival (<i>p</i> < 0.005).</p><p><strong>Conclusion: </strong>LSM by VCTE predicts HD following systemic treatment in advanced HCC. In patients with high LSM, Atezo/Bev increases HD risk, warranting careful treatment selection.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Models for Disease-Free Survival Analysis after Liver Resection for Hepatocellular Carcinoma: A Multicentric French Collaborative Study.","authors":"Rami Rhaiem, Ammar Abdo, Julien Calderaro, Safi Dokmak, Astrid Herrero, Cyprien Toubert, Perrine Zimmermann, Alexandra Heurgué, Camille Boulagnon-Rombi, Giuliana Amaddeo, Alain Luciani, Hélène Regnault, Marie Alaux, Mickael Lesurtel, Valérie Paradis, Daniele Sommacale, Olivier Soubrane, Stefano Caruso, Rudy Merieux, Reza Kianmanesh, Raffaele Brustia","doi":"10.1159/000550554","DOIUrl":"10.1159/000550554","url":null,"abstract":"<p><strong>Introduction: </strong>Liver resection (LR) is a potentially curative treatment of hepatocellular carcinoma (HCC), but early recurrence rates remain high reaching as high as 70%. Accurate prediction of disease-free survival (DFS) after LR is crucial to optimize patients' selection for clinical trials evaluating adjuvant strategies. This study assessed machine learning (ML) models for predicting DFS after LR for HCC.</p><p><strong>Methods: </strong>A total of 663 patients who underwent LR between 2010 and 2020 in 3 French HPB referral centers were analyzed. Three ML models - random survival forest (RSF), gradient boosting survival (GBS), and fast survival support vector machine (FSSVM) - were compared with the Cox proportional hazards regression model. Model performance was assessed using C-index and time-dependent area under the curve (AUC). External validation was performed using an independent cohort from a fourth center. Statistical comparisons between models were conducted using paired <i>t</i> tests.</p><p><strong>Results: </strong>After a median follow up of 52 months, recurrence occurred in 43% of patients and median DFS was 15 months. In the training cohort, RSF achieved the highest discrimination (C-index = 0.721 ± 0.027) and predictive accuracy (AUC = 0.768 ± 0.039) among the four evaluated models. Cox, GBS, and FSSVM showed comparable performance (C-index = 0.684-0.699; AUC = 0.718-0.745). Paired <i>t</i> tests demonstrated that RSF significantly outperformed Cox for both C-index (<i>p</i> = 0.023) and AUC (<i>p</i> = 0.039). In the external validation cohort, all ML models outperformed Cox regression, with RSF showing the highest performance (C-index 0.817, AUC 0.863), suggesting strong generalizability.</p><p><strong>Conclusions: </strong>RSF significantly improved DFS prediction compared with Cox regression and yielded the best discriminatory performance in both training and external validation cohorts. These findings highlight the value of ML-based survival models, particularly RSF, for enhancing individualized postoperative prognostication and refining patient selection for clinical trials evaluating adjuvant treatment to surveillance after LR for HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib as Second-Line Regimen after Atezolizumab plus Bevacizumab Combination Therapy.","authors":"Masatoshi Kudo","doi":"10.1159/000550634","DOIUrl":"10.1159/000550634","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"1-9"},"PeriodicalIF":10.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable Disease without Tumor Shrink Cannot Benefit from Surgery following Immune-Based Therapy in Potentially Resectable Hepatocellular Carcinoma.","authors":"Tian He, Bin Xu, Zi-Yue Yang, Shi-Qi Zhou, Zi-Yi Wang, Lu-Na Wang, Cheng-Jie Zhong, Huan-Chen Shi, Hui Li, Bo Hu, Xiao-Dong Zhu, Ying-Hao Shen, Qiang Gao, Jian Zhou, Jia Fan, Hui-Chuan Sun, Cheng Huang","doi":"10.1159/000550497","DOIUrl":"10.1159/000550497","url":null,"abstract":"<p><strong>Background: </strong>The criteria for identifying patients with potentially resectable hepatocellular carcinoma (HCC) at the baseline stage have helped identify patients who are more likely to achieve successful conversion. However, the suitable timing and selection of candidates for conversion surgery after systemic therapy remained underexplored.</p><p><strong>Methods: </strong>Based on real-world evidence, we analyzed a cohort of 222 patients with potentially resectable HCC treated with immune-based therapy between January 2019 and May 2024. The treatment response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and modified RECIST (mRECIST). Depth of response (DpR) was defined as the maximum tumor shrinkage from baseline, based on the sum of the longest diameters, as assessed by an independent review facility per RECIST v1.1. Conversely, stable disease (SD) with a DpR < 0%/> 0% was categorized as SD_shrink/SD_non-shrink. Survival outcomes were compared between patients who underwent surgery and those who did not, with different DpRs, and assessed using Kaplan-Meier methods.</p><p><strong>Results: </strong>A total of 85 patients with partial response (PR), 86 with SD_shrink, and 51 with SD_non-shrink were included in this study. Generally, patients who underwent surgery had a better prognosis than those who did not (<i>p</i> < 0.001). Patients with PR and SD_shrink significantly benefited from the surgery in both overall survival and event-free survival. However, patients with SD_non-shrink failed to obtain the same benefits. Additionally, surgical patients with a DpR <0% had a better prognosis than those with a DpR >0% (<i>p</i> < 0.001 and <i>p</i> = 0.004, respectively), whereas the survival of patients who did not undergo surgery did not differ.</p><p><strong>Conclusion: </strong>DpR is an important factor in choosing the right candidates and the timing of conversion therapy. Patients only at a DpR <0% receiving various immune-based treatments who met the \"potentially resectable\" criteria can benefit from surgical resection. These findings can help increase the success rate of conversion therapy in patients with advanced HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Adjusted Charlson Comorbidity Index Guides Risk Stratification for Hepatocellular Carcinoma Patients Treated with TACE Combined with Immune Checkpoint Inhibitors and Targeted Therapy: A Multicenter Retrospective Cohort Study.","authors":"Xiaohan Lin, Shiying Zhang, Meiching Ong, Jun Fang, Aibo Mu, Kui Wang, Li Xu, Xinyu Bi, Xiufeng Liu, Yongjun Chen, Huichuan Sun, Qi Ling","doi":"10.1159/000550356","DOIUrl":"10.1159/000550356","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) imposes a substantial global burden. Triple therapy including transarterial chemoembolization, immune checkpoint inhibitors, and targeted therapy offers survival benefits but increases toxicity risk. We aimed to evaluate the impact of age or its related comorbidities on the efficacy and safety of triple therapy.</p><p><strong>Methods: </strong>This multicenter retrospective study included 627 HCC patients receiving triple therapy from CLEAP database (2019-2023). Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. Treatment response and treatment-related adverse events (TRAEs) were the secondary endpoints. Cox/logistic regression models were used to assess the risk factors of outcomes.</p><p><strong>Results: </strong>Of 627 patients, 177 were classified as elderly (≥65 years) and 450 as younger (<65 years), as defined according to World Health Organization criteria. Elderly patients present with lower tumor burden compared with younger patients. After propensity score matching (1:2), two cohorts were comparable in objective response rate, disease control rate, PFS, OS, and grade ≥3 TRAEs. Age, either continuous or categorical data, was not associated with outcomes. In contrast, stratification by Charlson Comorbidity Index (CCI), there were significant outcome disparities for PFS and OS among low- (0-1), intermediate- (2-3), and high-risk (≥4) groups. The age-adjusted CCI (aCCI) could not only discriminate survival outcomes but also predict the risk of TRAEs among low- (0-3), intermediate- (4-5), and high-risk (≥6) groups. Multivariable analyses demonstrated that high aCCI score (≥6) independently predicted shorter PFS (hazard ratio: 1.36, <i>p</i> = 0.02) and OS (hazard ratio: 1.75, <i>p</i> = 0.001) and increased grade ≥ 3 TRAEs (odds ratio: 1.96, <i>p</i> = 0.005).</p><p><strong>Conclusion: </strong>aCCI was a potent predictor of efficacy and safety in triple therapy for HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic FIB-4 Score Changes and HCC Risk in Patients with MASLD and Elevated Liver Enzymes: A Nationwide Cohort Study.","authors":"Yee Hui Yeo, Hsiu J Ho, Tsai-Wei Huang, Teng-Yu Lee, Ju Dong Yang, George Cholankeril, Chien-Jen Chen, Hawi-I Yang, Chuen-Fei Chen, Hung-Chuen Chang, Chun-Ying Wu","doi":"10.1159/000550360","DOIUrl":"10.1159/000550360","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) can develop in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) without cirrhosis, especially in those with elevated liver enzymes. However, there is currently no low-cost, scalable screening tool for this population. To address this need, we investigated the association between serial changes in FIB-4 (fibrosis-4) scores over a 3-year period and the risk of developing HCC in a large, diverse cohort of patients with MASLD without cirrhosis.</p><p><strong>Methods: </strong>This study utilized a nationwide cohort from the National Health Insurance Research Database (NHIRD), including 810,698 patients with MASLD who had demographic and laboratory data at baseline and at least 3 years of follow-up. FIB-4 scores were analyzed to assess transitions between low-risk (<1.45), indeterminate-risk (1.45-2.67), and high-risk (>2.67) categories over time. Competing risks for HCC and mortality were modeled to estimate the sub-distribution hazard ratios (SHRs).</p><p><strong>Results: </strong>Changes in FIB-4 scores over time provided superior predictive accuracy compared to one-time measurement. Individuals with persistent high FIB-4 (high-to-high group) had a 14-fold higher risk of developing HCC (adjusted SHR [aSHR] 13.91, 95% CI: 11.94-16.20) compared to those with stably low FIB-4 (low-to-low group), while those with improved scores (high-to-low and high-to-indeterminate groups) had a lower risk compared to the high-to-high group. Worsening FIB-4 scores, as shown in the low-to-indeterminate group (aSHR 2.22, 95% CI: 1.93-2.57 or the low-to-high group (aSHR 4.75, 95% CI: 3.38-6.68), were associated with progressively increased risks of HCC compared to the low-to-low group. In contrast, when compared to the high-to-high group, those with improved FIB-4 scores, including the high-to-indeterminate group (aSHR 0.41, 95% CI: 0.35-0.48) and the high-to-low group (aSHR 0.25, 95% CI: 0.15-0.42), exhibited reduced HCC risks.</p><p><strong>Conclusion: </strong>Serial FIB-4 measurements offer greater accuracy in identifying individuals at high risk for HCC in non-cirrhotic MASLD Asians with elevated liver enzymes, with HCC surveillance warranted in high-risk groups.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1b Study of Lenvatinib plus Nivolumab in Patients with Unresectable Hepatocellular Carcinoma.","authors":"Masafumi Ikeda, Masatoshi Kudo, Kenta Motomura, Takuji Okusaka, Naoya Kato, Takashi Hisai, Hiroki Ikezawa, Sari Shiba, Taisuke Hoshi, Masataka Kuroda, Hiromitsu Kumada, Masahiro Kobayashi","doi":"10.1159/000549681","DOIUrl":"10.1159/000549681","url":null,"abstract":"<p><strong>Introduction: </strong>Despite recent advances in treatment for unresectable hepatocellular carcinoma (uHCC), median overall survival (OS) in the first-line setting across immune-based combination therapies has plateaued at 16<b>-</b>24 months. Evaluation of potentially more potent therapies is warranted. We report results of the first prospective phase 1b study of lenvatinib (multi-kinase inhibitor) + nivolumab (anti-programmed death receptor1 antibody) for treating advanced uHCC.</p><p><strong>Methods: </strong>This open-label study was conducted in Japan among adults (≥20 years) with histologically/cytologically confirmed HCC. Patients received monotherapy-approved doses of either 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) oral lenvatinib once daily + 240 mg intravenous nivolumab every 2 weeks (days 1 and 15) in 4-week cycles. Part 1 planned to enroll 6 patients to evaluate the tolerability of lenvatinib+nivolumab. Part 2 evaluated safety and preliminary antitumor activity. Primary endpoints were dose-limiting toxicities (DLTs; part 1 only) and safety. Secondary endpoints were objective response rate (ORR) and pharmacokinetics of lenvatinib and nivolumab. Additional exploratory endpoints (including OS and progression-free survival [PFS]; part 2 only) were assessed.</p><p><strong>Results: </strong>No DLT was observed among patients (<i>n</i> = 6) in part 1. Treatment-related adverse events (TRAEs) were observed in all patients (<i>n</i> = 30) in part 1 and 2. The most common TRAEs were palmar-plantar erythrodysesthesia syndrome (60%), dysphonia (53.3%), and decreased appetite (50.0%). Distributions of lenvatinib AUC_(0-t) were similar to those observed for lenvatinib in HCC previously and were within the distributions of AUC_(0-τ) observed with lenvatinib monotherapy in the REFLECT trial. ORR by mRECIST per investigator review was 66.7% in part 1 and 79.2% in part 2. In part 2, median PFS was 9.07 months by mRECIST per investigator review, and median OS was 26.94 months.</p><p><strong>Conclusion: </strong>Lenvatinib+nivolumab was well tolerated and had encouraging antitumor activity in patients with advanced uHCC in this phase 1b study.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12956365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No More Detours: Hepatopulmonary Shunt Reduction in a Patient with Hepatocellular Carcinoma after Treatment with Bevacizumab.","authors":"Matthias Jeschke, Julia M Schütte, Stephan Himmen, Ken Herrmann, Hannah L Steinberg-Vorhoff, Jens M Theysohn, Jan Best, Hartmut H-J Schmidt, Leonie S Jochheim","doi":"10.1159/000548565","DOIUrl":"10.1159/000548565","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment options for intermediate-stage hepatocellular carcinoma (HCC) include transarterial radioembolization (TARE) and systemic treatment. Currently, in the absence of contraindications, first-line systemic therapies include combinations of immune checkpoint inhibitors with anti-angiogenic agents or different checkpoint inhibitors. Combinations of TARE and systemic treatment are being investigated for synergistic effects due to a boosting of the immune response. However, a high hepatopulmonary shunt (HPS) fraction - abnormal passage of blood from the hepatic vasculature to the pulmonary circulation resulting from the formation of abnormal vasculature within the tumor - precludes some patients from receiving TARE due to the risk of nontarget lung radiation. Here, we present a case in which treatment of a patient with atezolizumab and bevacizumab led to a significant reduction in HPS, enabling locoregional treatment of the tumor while the tumor did not respond to systemic treatment alone according to the mRECIST criteria.</p><p><strong>Case presentation: </strong>Here, we report the case of a patient with intermediate-stage HCC who received systemic treatment with atezolizumab and bevacizumab due to a high HPS fraction of 42% precluding him from treatment with radioembolization. Despite eventually showing tumor progression to systemic treatment based on clinical and radiological evaluation, the lung shunt fraction was markedly reduced by the systemic treatment to only 3.4%, enabling successful treatment of the tumor with radioembolization.</p><p><strong>Conclusion: </strong>The anti-angiogenic effects of bevacizumab may reduce HPS in patients with intermediate-stage HCC, thereby extending the utility of TARE. In patients who do not respond to systemic treatment and who are amenable to treatment with TARE due to tumor stage, repeated measurements of HPSF might be considered after treatment with bevacizumab.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12823128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.","authors":"Yaming Liu","doi":"10.1159/000550163","DOIUrl":"10.1159/000550163","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) associated with metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly identified in non-cirrhosis livers, representing a distinct clinical challenge. Unlike other etiologies, up to 50% of MASLD-related HCC arises without cirrhosis, conferring a significantly elevated risk and bypassing the traditional cirrhosis-carcinoma sequence.</p><p><strong>Summary: </strong>This review delineates the unique pathogenesis of non-cirrhotic MASLD-HCC, focusing on the interplay between metabolic dysregulation, chronic inflammation, and a characteristic immunosuppressive tumor microenvironment (TME). We synthesize evidence on how immune dysregulation - particularly involving dysfunctional CD8+ T cells and an altered myeloid compartment - facilitates hepatocarcinogenesis independent of advanced fibrosis. The roles of genetic susceptibility (e.g., <i>PNPLA3</i> and <i>TM6SF2</i> variants), gut-liver axis disruption, and distinct molecular traits are also examined. We further evaluate emerging biomarkers for risk stratification and discuss the implications of the non-cirrhotic MASH immune contexture for responses to immunotherapy.</p><p><strong>Key messages: </strong>Non-cirrhotic MASLD-HCC is a distinct oncogenic entity driven by metabolic-immune interplay. Its recognition necessitates a shift in clinical paradigm: (1) surveillance strategies must incorporate metabolic and genetic risk factors beyond cirrhosis; (2) the unique TME may predict immunotherapy efficacy, urging etiology-specific trial design; and (3) a precision oncology framework integrating molecular subtyping and biomarker profiling is essential for early detection and tailored management of this growing patient population.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"631-645"},"PeriodicalIF":10.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12846323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Biomarker Panels in the Surveillance and Monitoring of Hepatocellular Carcinoma: Consensus Statements from an International Delphi Panel.","authors":"Amit G Singal, Hidenori Toyoda, Tawesak Tanwandee, Pisit Tangkijvanich, Chee-Kiat Tan, Ian Homer Cua, Diana Alcantara-Payawal, Tung-Hung Su, Nguyen Dinh Song Huy, Hiroyuki Yamada, Masatoshi Kudo","doi":"10.1159/000550100","DOIUrl":"10.1159/000550100","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) surveillance is recommended using a combination of abdominal ultrasound plus alpha-fetoprotein (AFP) in patients with chronic hepatitis B or cirrhosis from any etiology. However, this strategy is limited by suboptimal sensitivity for early-stage HCC, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease. Phase 2 and phase 3 biomarker studies have reported the promise of novel blood-based biomarkers, including AFP, des-gamma-carboxy prothrombin, and lens culinaris agglutinin-reactive AFP (AFP-L3). Biomarker panels, such as the GALAD score, GAAD, and ASAP combine these biomarkers plus age and gender into biomarker panels. A panel of 10 experts from Asia and the USA convened to discuss the clinical utility of these biomarkers for detecting early-stage HCC. The experts agreed that biomarker panels have shown higher sensitivity than each individual biomarker and showed promise for early-stage HCC detection, particularly in those with a high proportion of patients with obesity and MASLD and geographies with insufficient access to high-quality ultrasound. However, biomarkers require prospective validation in clinical utility trials demonstrating net benefit in patients with cirrhosis, and implementation may face challenges including widespread access to testing, broader insurance coverage, and improving awareness among physicians and patients.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}