Hepatology Research最新文献

{"title":"Associations of serum carotenoids with cardiovascular disease mortality among patients with metabolic dysfunction-associated steatotic liver disease.","authors":"Qian-Qian Wang, Jing Zhu, Lin-Jun Miao, Si-Ang Lv, Guo-Yin Shen, Jun Wu","doi":"10.1111/hepr.14215","DOIUrl":"https://doi.org/10.1111/hepr.14215","url":null,"abstract":"<p><strong>Aim: </strong>High cardiovascular disease (CVD) mortality occurred among metabolic dysfunction-associated steatotic liver disease (MASLD) patients with few approved therapies. The aim of this study was to reveal the associations of serum carotenoid concentrations with CVD mortality among MASLD patients.</p><p><strong>Methods: </strong>The two prospective cohort analyses included 1175 MASLD patients from the National Health and Nutrition Examination Survey (NHANES) and 1725 MASLD patients from NHANES III. CVD mortality was ascertained through December 31, 2019. Multivariable Cox proportional hazards regression analysis was carried out to evaluate the associations of serum carotenoid levels with CVD mortality.</p><p><strong>Results: </strong>After multivariable adjustment, per one-unit increment in natural log-transformed serum β-cryptoxanthin was associated with an 85% lower risk of CVD mortality (p = 0.03) among MASLD patients aged <60 years from NHANES and a 92% lower risk of CVD mortality (p = 0.003) among MASLD patients aged <60 years from NHANES III. The adjusted HRs (95% CIs) across tertiles of serum β-cryptoxanthin concentrations were 1.00 (reference), 0.55 (0.12-2.41), 0.02 (0.002-0.24), P trend = 0.03 and 1.00 (reference), 0.47 (0.14-1.58), 0.05 (0.01-0.31), P trend = 0.002, among MASLD patients aged <60 years from NHANES and NHANES III, respectively.</p><p><strong>Conclusions: </strong>In MASLD patients aged <60 years, high serum β-cryptoxanthin concentrations were inversely associated with CVD mortality.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to evaluate the therapeutic efficacy of durvalumab and tremelimumab combination therapy in hepatocellular carcinoma.","authors":"Tetsu Tomonari, Shigeo Shimose, Issei Saeki, Joji Tani, Yuichi Honma, Takanori Ito, Mamiko Takeuchi, Takehito Naito, Yasuto Takeuchi, Ryu Sasaki, Kyo Sasaki, Takeshi Hatanaka, Satoru Kakizaki, Yuki Kanayama, Atsushi Naganuma, Norikazu Tanabe, Hironori Tanaka, Yutaka Kawano, Yasushi Sato, Sohji Nishina, Hisamitsu Miyaaki, Motoyuki Otsuka, Hiroki Kawashima, Masaru Harada, Hideki Kobara, Taro Takami, Takumi Kawaguchi, Tetsuji Takayama","doi":"10.1111/hepr.14212","DOIUrl":"https://doi.org/10.1111/hepr.14212","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real-world clinical practice, characterize \"stable disease (SD),\" and identify SD responders (SD-R) who benefit from Dur + Tre treatment.</p><p><strong>Methods: </strong>This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u-HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first-line and 117 later-line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression-free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders.</p><p><strong>Results: </strong>Disease control rate (DCR) and PFS were significantly better in the first-line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤-10% were classified as SD-R, as they had long-term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD-R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD-R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11).</p><p><strong>Conclusions: </strong>In real-world clinical practice, Dur + Tre is highly effective as a first-line treatment for u-HCC. Additionally, patients with SD who met the SD-R criteria (PFS ≥84 days or RECIST DOR ≤-10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic alterations in hepatocellular carcinoma after sustained virological response in relation to the molecular characterization of metabolic diseases.","authors":"Fukiko Kawai-Kitahata, Yasuhiro Asahina, Sei Kakinuma, Kento Inada, Tomohiro Mochida, Keiya Watakabe, Tsubasa Nobusawa, Taro Shimizu, Jun Tsuchiya, Masato Miyoshi, Shun Kaneko, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Yuko Kinowaki, Daisuke Ban, Shinji Tanaka, Tatsuhiko Anzai, Shinichi Takano, Shinya Maekawa, Nobuyuki Enomoto, Ryuichi Okamoto","doi":"10.1111/hepr.14214","DOIUrl":"https://doi.org/10.1111/hepr.14214","url":null,"abstract":"<p><strong>Aim: </strong>The mechanism of hepatocarcinogenesis after sustained virological response (SVR) in hepatitis C virus (HCV) patients is unclear. We compared gene profiles of hepatocellular carcinoma (HCC) between HCV-SVR, steatotic liver disease (SLD), and HCV-non-SVR patients.</p><p><strong>Methods: </strong>This study analyzed 126 resected HCCs from patients with HCV and SLD, classifying them as HCV-SVR (n = 22), HCV-non-SVR (n = 56), and SLD (n = 48). Deep sequencing of 2910 hotspots in 55 cancer-related genes was conducted to examine mutations and copy number variations in both cancerous and background liver tissues.</p><p><strong>Results: </strong>The HCV-SVR group comprised more patients who consumed alcohol (45.5% vs. 15.7%, p = 0.008), were obese (54.5% vs. 17.9%, p = 0.002), and had dyslipidemia (18.2% vs. 3.6%, p = 0.029) and hyperuricemia (18.2% vs. 3.6%, p = 0.029) than the HCV-non-SVR group. Mutational profiling of the HCV-SVR HCC showed significantly lower alteration rates of AXIN1 (13.6% vs. 42.9%, p = 0.016), ARID2 (9.1% vs. 39.3%, p = 0.013), and TP53 (9.1% vs. 32.1%, p = 0.030) than HCV-non-SVR patients. Compared with HCV-non-SVR-HCC, SLD-HCCs showed significantly lower rates of TERT promoter mutations (62.5% vs. 85.7%, p = 0.004), ARID2 alterations (12.5% vs. 39.3%, p = 0.003), and AXIN1 alterations (12.5% vs. 42.9%, p = 0.002). HCV-SVR/MASH/MASLD/ALD-HCC had significantly lower alteration rates of the Wnt/β-catenin (41.4% vs. 60.7%, p = 0.048) and chromatin remodeling pathways (27.1% vs. 48.2%, p = 0.026) than HCV-non-SVR-HCC.</p><p><strong>Conclusions: </strong>HCV-SVR HCC is linked to alcohol use and metabolic diseases, showing a mutational profile similar to SLD-HCC.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The EZ-ALBI score as a prognostic tool for outcomes after resection of small hepatocellular carcinoma (≤3 cm).","authors":"Tomonari Shimagaki, Keishi Sugimachi, Takahiro Tomino, Emi Onishi, Takeo Toshima, Shinji Itoh, Takashi Maeda, Tomoharu Yoshizumi, Masaru Morita","doi":"10.1111/hepr.14210","DOIUrl":"https://doi.org/10.1111/hepr.14210","url":null,"abstract":"<p><strong>Purpose: </strong>Liver function is a key prognostic factor in patients with hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI) score is an objective method to assess liver function severity, but its calculation is complex and challenging to implement in clinical practice. This study evaluated the prognostic utility of the EZ-ALBI score, which uses a simpler and more accessible calculation method, in patients undergoing resection for small HCC (≤3 cm).</p><p><strong>Methods: </strong>The study included 1161 patients who underwent hepatectomy for small HCC. Data from these patients were analyzed, with 837 patients in dataset A and 324 in dataset B, considering the differences in surgical procedures between facilities.</p><p><strong>Results: </strong>There was a strong correlation between the ALBI and EZ-ALBI scores across all patients, with a correlation coefficient of 0.974 (p < 0.0001). Comparison between the EZ-ALBI Grade 1 (n = 647) and Grade 2 (n = 514) groups showed that Grade 2 had significantly poorer liver function, shorter operative time, and higher rates of postoperative complications. In dataset A, patients in the EZ-ALBI Grade 2 group had significantly worse overall survival than those in Grade 1 (p < 0.0001). Similar trends were observed in dataset B, where Grade 2 was associated with significantly worse disease-free survival and overall survival. Univariate and multivariate analyses identified the EZ-ALBI score as an independent prognostic factor for OS in both datasets, with Grade 1 patients showing a better prognosis.</p><p><strong>Conclusion: </strong>The EZ-ALBI score is a valuable prognostic tool for assessing outcomes after resection of small HCC.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Ro52/TRIM21 autoantibodies predict Sjögren's syndrome in patients with primary biliary cholangitis.","authors":"Marie Louise Næstholt Dahl, Trine-Line Korsholm, Jakob Hauge Mikkelsen, Malene Hvid, Ayad Babaee, Matias Hauge Böttcher, Jesper Bach Hansen, Peter Holland-Fischer, Christian Brix Folsted Andersen, Henning Grønbæk, Bent Deleuran","doi":"10.1111/hepr.14213","DOIUrl":"https://doi.org/10.1111/hepr.14213","url":null,"abstract":"<p><strong>Background and aims: </strong>Sjögren's syndrome is a common comorbidity in patients with primary biliary cholangitis (PBC). Anti-Ro52 autoantibodies against the protein TRIM21 are often seen in Sjögren's syndrome. TRIM21 consists of four domains (PRY/SPRY, Coiled-Coil, B-box, and RING domain), each with a specific function. We hypothesized that patients with PBC and concomitant autoantibodies against TRIM21 had a higher risk of developing Sjögren's syndrome.</p><p><strong>Methods: </strong>Using ELISA, we analyzed plasma from 236 Danish patients with PBC. Binomial regression assessed the risk rates between demographics, serologic variables, PBC-40 results, and autoantibody positivity.</p><p><strong>Results: </strong>Forty patients (16.9%) tested positive for anti-Ro52 autoantibodies, with 23 (9.7%) samples positive against Coiled-Coil, 12 against PRY/SPRY (5.1%), and 10 against RING (4.2%). Increased IgG plasma levels, reports of dry mouth, and a diagnosis of Sjögren's syndrome increased the risk of both anti-Ro52 and all domain autoantibodies. In the anti-Ro52 positive subgroup, no less than 14 undiagnosed patients met the criteria for Sjögren's syndrome.</p><p><strong>Conclusions: </strong>We observed a 16.9% positivity of anti-Ro52 autoantibodies and an association between having these autoantibodies and elevated IgG, the symptom dry mouth, and having Sjögren's syndrome. Furthermore, we found a sizable undiagnosed group of Sjögren's patients in the anti-Ro52 positive subgroup. Our results suggest that Sjögren's patients are underdiagnosed in patients with PBC. We propose that patients with PBC be tested for anti-Ro52 autoantibodies and, if positive, referred for rheumatological examination.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limitations of the proposed lymph node classification in intrahepatic cholangiocarcinoma.","authors":"Susumu Eguchi","doi":"10.1111/hepr.14209","DOIUrl":"https://doi.org/10.1111/hepr.14209","url":null,"abstract":"<p><p>The study by Kurimoto et al. represents a notable contribution to the challenging field of intrahepatic cholangiocarcinoma (ICC), particularly in the surgical management of node-positive cases. By focusing on the prognostic impact of both lymph node (LN) distribution and yield, the authors propose a new framework for defining \"advanced\" LN metastasis in ICC. Their multicenter design, high rate of adequate LN dissection (LND), and meticulous data analysis make this proposal both timely and thought-provoking. Nevertheless, important considerations remain unresolved. The anatomical variability of lymphatic drainage, potential post-treatment modifications, and the role of preoperative imaging all impact the real-world applicability of their model. Future prospective studies incorporating standardized PET imaging, lymphatic mapping techniques, and more detailed anatomical stratification-including mediastinal and thoracic nodes-will be essential in refining and validating this classification.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes in the characteristics of hepatocellular carcinoma among Japanese patients: Increasing incidence of cases without liver fibrosis.","authors":"Fujimasa Tada, Atsushi Hiraoka, Hideko Ohama, Yuka Kimura, Ayaka Nakamura, Kana Matsuoka, Takuya Matsuda, Kanako Kato, Kazuya Murakawa, Kei Onishi, Hirofumi Izumoto, Shogo Kitahata, Kozue Kanemitsu-Okada, Tomoe Kawamura, Taira Kuroda, Jun Hanaoka, Jota Watanabe, Hiromi Ohtani, Teruki Miyake, Osamu Yoshida, Masashi Hirooka, Hideki Miyata, Eiji Tsubouchi, Masanori Abe, Bunzo Matsuura, Tomoyuki Ninomiya, Yoichi Hiasa","doi":"10.1111/hepr.14208","DOIUrl":"https://doi.org/10.1111/hepr.14208","url":null,"abstract":"<p><strong>Aim: </strong>Dynamic changes in the characteristics of hepatocellular carcinoma (HCC) have been observed owing to the development of antiviral therapies and an aging society. This study aimed to evaluate the clinical features and prognosis of patients with HCC but without liver fibrosis (F0 HCC).</p><p><strong>Methods: </strong>From 2000 to 2023, 505 patients with HCC who underwent surgical resection as an initial treatment were enrolled and categorized into the F0 (n = 59) and fibrosis (F1-4, n = 446) groups based on their liver fibrosis status. Clinical features, tumor factors, and survival outcomes were retrospectively analyzed. Inverse probability weighting with propensity scores was used to control for baseline differences between the groups.</p><p><strong>Results: </strong>The proportion of F0 HCC (G1/G2/G3/G4 = 1.3/7.0/13.3/20.0%, p < 0.001) and nonviral (NBNC) HCC cases increased steadily over the study period. Patients in the F0 group were older and more likely to show solitary giant tumors; however, no significant differences were observed in tumor differentiation, microvascular invasion, or intrahepatic metastasis between the groups. After adjusting for baseline characteristics, the F0 group showed significantly improved overall survival and recurrence-free survival compared to the fibrosis group (adjusted median OS: not achieved vs. 90.6 months, p < 0.001; adjusted median RFS: 67.2 vs. 35.1 months, p < 0.001).</p><p><strong>Conclusions: </strong>The increasing prevalence of NBNC HCC has contributed to an increase in the number of F0 HCC cases, demonstrating favorable prognoses post-curative treatment. Screening strategies tailored to detect F0 HCC are urgently needed to optimize outcomes, particularly for older patients and those with large tumors.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor receptor 2 alterations in intrahepatic cholangiocarcinoma: Prevalence and clinical implications in Asian populations.","authors":"Kyoko Oura, Asahiro Morishita, Hideki Kobara","doi":"10.1111/hepr.14207","DOIUrl":"https://doi.org/10.1111/hepr.14207","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative evaluation of tumor signal heterogeneity on gadoxetic acid-enhanced magnetic resonance imaging as a predictor of postoperative survival and antitumor immunity in hepatocellular carcinoma.","authors":"Shunsuke Doi, Satoshi Yasuda, Minako Nagai, Kota Nakamura, Yasuko Matsuo, Taichi Terai, Yuichiro Kohara, Takeshi Sakata, Toshihiro Tanaka, Kiyoyuki Minamiguchi, Tetsuya Tachiiri, Hideki Kunichika, Naoki Ozu, Masayuki Sho","doi":"10.1111/hepr.14204","DOIUrl":"https://doi.org/10.1111/hepr.14204","url":null,"abstract":"<p><strong>Aim: </strong>We investigated the efficacy of quantitative evaluation of tumor signal heterogeneity on gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis and antitumor immunity in patients with hepatocellular carcinoma (HCC) undergoing liver resection.</p><p><strong>Methods: </strong>A total of 297 patients who underwent curative resection for primary HCC were included. Tumor signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantified as the coefficient of variation (CV), calculated as the standard deviation divided by the mean signal intensity. Patients were classified into homogeneous (low CV) and heterogeneous (high CV) groups based on a cutoff value of 0.16 from receiver operating characteristic curve analysis. Tumor-infiltrating CD4+ and CD8+ T cells and PD-L1 expression were assayed by immunohistochemistry, and their associations with tumor signal heterogeneity were evaluated.</p><p><strong>Results: </strong>Among the 297 patients, 116 (39.1%) were classified into the heterogeneous group. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly lower in the heterogeneous group (p < 0.001 for both). Multivariate analysis identified heterogeneous group as an independent prognostic factor for OS and RFS (p < 0.001 and p = 0.012, respectively). Extrahepatic recurrence was significantly more frequent in the heterogeneous group (18.1% vs. 7.7%, p = 0.024). CD4+ and CD8+ T cells were significantly decreased, and the PD-L1 positivity rate was significantly lower in the heterogeneous group (p < 0.001 for all).</p><p><strong>Conclusions: </strong>The quantitative evaluation of tumor signal heterogeneity in the HBP of EOB-MRI using CV is useful for predicting postoperative prognosis in patients with HCC. Tumor signal heterogeneity may also reflect impaired local immunity and an immunologically \"cold\" tumor.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of preoperative peripheral blood GPC3-positive circulating tumor cells in subclassification of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma: a retrospective cohort study.","authors":"Yosuke Namba, Tsuyoshi Kobayashi, Yoshito Hirata, Takeshi Tadokoro, Sotaro Fukuhara, Ko Oshita, Naruhiko Honmyo, Ryosuke Nakano, Hiroshi Sakai, Seiichi Shimizu, Shintaro Kuroda, Hiroyuki Tahara, Masahiro Ohira, Kentaro Ide, Yuka Tanaka, Hideki Ohdan","doi":"10.1111/hepr.14211","DOIUrl":"https://doi.org/10.1111/hepr.14211","url":null,"abstract":"<p><strong>Aim: </strong>The treatment strategy for hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage B, representing the intermediate stage, remains unclear. This study aimed to evaluate the utility of glypican-3 (GPC3)-positive circulating tumor cells (CTCs) in subclassifying BCLC stage B.</p><p><strong>Methods: </strong>The present retrospective cohort study included patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and March 2022. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS).</p><p><strong>Results: </strong>A total of 338 patients were included in the analysis. GPC3-positive CTCs were significantly associated with a positive rate of microscopic portal vein invasion. In BCLC stages 0/A, there was no significant difference in survival rates between patients with GPC3-positive CTC counts. However, in BCLC stage B, both OS and RFS were significantly lower in the high number of GPC3-positive CTC group (p = 0.02 and p = 0.03, respectively). Further analysis using a four-group classification based on BCLC stage and GPC3-positive CTC count revealed that both OS and RFS were significantly lower in BCLC stage B with the high number of GPC3-positive CTC group (p < 0.01). Multivariate analysis identified Child-Pugh B status and beyond up-to-7 criteria as independent risk factors for poor OS (p = 0.01 and p = 0.04, respectively). For RFS, beyond up-to-7 criteria and a high number of GPC3-positive CTCs were identified as independent predictive factors (p = 0.04). Based on BCLC stage B, combining GPC3-positive CTCs with the up-to-7 criteria significantly stratified OS and RFS.</p><p><strong>Conclusions: </strong>Glypican-3-positive CTCs are effective for subclassifying BCLC stage B HCC. When combined with the up-to-7 criteria, they may help with the development of new treatment strategies.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}