Hepatology Research最新文献

{"title":"Response to the Letter “Steatotic Liver Disease: A Key Related Risk Factor in the Emergence of Metabolic Syndrome-Related Disorders”","authors":"Yoshihiro Kamada","doi":"10.1111/hepr.70171","DOIUrl":"10.1111/hepr.70171","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1182-1184"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490466","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":"Response to the Letter “Steatotic Liver Disease and the ‘Point of No Return’ in the Development of Metabolic Disorders”","authors":"Yoshihiro Kamada","doi":"10.1111/hepr.70167","DOIUrl":"10.1111/hepr.70167","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1179-1181"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493443","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":"Impact of Treatment Response to Anticoagulant Therapy on Liver-Related Events in Patients With Cirrhosis and Portal Vein Thrombosis","authors":"Atsushi Maeda,&nbsp;Yuki Tahata,&nbsp;Hayato Hikita,&nbsp;Hisashi Ishida,&nbsp;Takayuki Yakushijin,&nbsp;Masanori Nakahara,&nbsp;Kazuyoshi Ohkawa,&nbsp;Fumihiko Nakanishi,&nbsp;Sadaharu Iio,&nbsp;Ryotaro Sakamori,&nbsp;Mitsuru Sakakibara,&nbsp;Masanori Miyazaki,&nbsp;Yuta Myoin,&nbsp;Kazuki Maesaka,&nbsp;Kumiko Shirai,&nbsp;Kazuhiro Murai,&nbsp;Yuki Makino,&nbsp;Yoshinobu Saito,&nbsp;Takahiro Kodama,&nbsp;Tetsuo Takehara","doi":"10.1111/hepr.70166","DOIUrl":"10.1111/hepr.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The effect of treatment response to anticoagulant therapy on prognosis of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-one patients with cirrhosis and first PVT treated with intravenous anticoagulant therapy between January 2015 and April 2018 at 10 Japanese hospitals were included. Treatment response was defined based on change in size of PVT after anticoagulant therapy as the following: complete response (CR, 0%), partial response (PR, ≤ 50%), stable disease (SD, 51%–100%), and progressive disease (PD, ≥ 101%). CR and PR were combined as the effective group and SD and PD formed as the ineffective group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age was 69 years, and 56% of the patients had Child–Pugh class B. Overall, 5 (12%) achieved CR, 22 (54%) achieved PR, 12 (29%) had SD and 2 (5%) had PD. During a median follow-up of 31.8 months from the date of assessment of treatment response, 17 patients died. The overall survival rates at 1- and 3-year were 82.5% and 65.1%, respectively. In the multivariate analysis, the model for end-stage liver disease-Na score was significantly associated with overall survival, whereas treatment response was not significant. Twenty-five patients experienced liver-related events with hospitalization, and the 3-year cumulative rate of liver-related events was 63.9%. In the multivariate analysis, treatment response was significantly associated with liver-related events. The 3-year cumulative rates of liver-related events were 56.7% and 75.5% in the effective and ineffective groups, respectively (<i>p</i> = 0.008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among patients with cirrhosis, treatment response to anticoagulant therapy for PVT correlated with the incidence of liver-related hospitalization events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1152-1160"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Etiological Shifts and the Rising Burden of Non–B Non–C Hepatocellular Carcinoma on Surveillance and Prognosis: Insights From a 20-Year Retrospective Observational Study","authors":"Yoko Yoshimaru,&nbsp;Katsuya Nagaoka,&nbsp;Hiroko Setoyama,&nbsp;Takahiro Mizuta,&nbsp;Toshinori Toyota,&nbsp;Daiki Maeda,&nbsp;Sotaro Kurano,&nbsp;Kentaro Tanaka,&nbsp;Hiroki Inada,&nbsp;Satoshi Narahara,&nbsp;Etsuko Iio,&nbsp;Maiko Nagaoka,&nbsp;Yukiko Nakai,&nbsp;Takehisa Watanabe,&nbsp;Haruki Uoshima,&nbsp;Masakuni Tateyama,&nbsp;Motohiko Tanaka,&nbsp;Yasuhito Tanaka","doi":"10.1111/hepr.70161","DOIUrl":"10.1111/hepr.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study evaluated surveillance impact on outcomes in 1143 patients with first-onset hepatocellular carcinoma (HCC) treated between 2003 and 2023, focusing on the etiological shift toward non-B non-C (NBNC) liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were stratified by etiology: hepatitis B virus (HBV, <i>n</i> = 182), hepatitis C virus (HCV, <i>n</i> = 555), and NBNC (<i>n</i> = 375). Surveillance was defined as ≥ 1 annual imaging examination. We assessed surveillance impact on overall survival (OS) using multivariable Cox regression analysis and analyzed diagnostic modalities and tumor markers stratified by etiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over the 20-year period, HCV-related HCC decreased whereas NBNC––HCC significantly increased, mainly driven by SLD. A total of 654 patients (58.8%) underwent regular surveillance. Compared with nonsurveilled patients, surveillance patients had significantly higher early-stage diagnosis (79.8% vs. 36.9% and <i>p</i> &lt; 0.001) and curative treatment rates (52.8% vs. 21.6% and <i>p</i> &lt; 0.001). Multivariable analysis confirmed surveillance as an independent prognostic factor for OS (<i>n</i> = 1,085, hazard ratio: 0.61, and <i>p</i> &lt; 0.001). Notably, in the NBNC group, nearly 60% of early-stage cases were detected via CT/MRI, significantly higher than in viral etiologies. Furthermore, des-gamma-carboxy prothrombin (DCP)-only positivity was highest in patients with NBNC (22.4%), whereas AFP-only positivity was rare (4.5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although regular surveillance provides a robust survival benefit independent of liver function, a critical “surveillance gap” persists in the rapidly expanding NBNC population. The high reliance on CT/MRI and DCP in NBNC patients suggests that standard ultrasound and AFP-based strategies may have limitations in this group. Etiology-specific protocols integrating cross-sectional imaging and combined biomarkers warrant further consideration to bridge this gap.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1089-1100"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473476","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":"Ablation-Based Salvage Strategy at Disease Progression After Initial Disease Control With Atezolizumab/Bevacizumab in Hepatocellular Carcinoma","authors":"Kazuya Kariyama,&nbsp;Kazuhiro Nouso,&nbsp;Atsushi Hiraoka,&nbsp;Fujimasa Tada,&nbsp;Hideko Ohama,&nbsp;Hidenori Toyoda,&nbsp;Satoshi Yasuda,&nbsp;Toshifumi Tada,&nbsp;Kazunari Tanaka,&nbsp;Kunihiko Tsuji,&nbsp;Ei Itobayashi,&nbsp;Akemi Tsutsui,&nbsp;Koichi Takaguchi,&nbsp;Michitaka Imai,&nbsp;Toru Ishikawa,&nbsp;Takeshi Hatanaka,&nbsp;Yuki Kanayama,&nbsp;Satoru Kakizaki,&nbsp;Atsushi Naganuma,&nbsp;Yoshihide Ueda,&nbsp;Tomomitsu Matono,&nbsp;Hideyuki Tamai,&nbsp;Junpei Okamura,&nbsp;Hironori Tanaka,&nbsp;Yutaka Yata,&nbsp;Akiko Wakuta,&nbsp;Masatoshi Kudo,&nbsp;Takashi Kumada","doi":"10.1111/hepr.70193","DOIUrl":"10.1111/hepr.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with unresectable hepatocellular carcinoma (HCC) who initially achieve disease control with atezolizumab plus bevacizumab (Atez/Bev) eventually develop progressive disease (PD). Treatment is usually shifted to subsequent systemic therapy, whereas ablation is rarely considered. We investigated whether ablation at PD could serve as a salvage option in selected patients after initial disease control with Atez/Bev.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From a multicenter database involving 16 institutions, we identified 186 patients with unresectable HCC who achieved partial response or stable disease with first-line Atez/Bev and subsequently developed PD between 2020 and 2025. Postprogression survival (PPS) and overall survival (OS) were compared between ablation and nonablation groups using propensity score matching (PSM). Multivariable Cox regression was performed for both OS and PPS. Inverse probability of treatment weighting (IPTW) and landmark analysis were used as sensitivity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After PSM, 20 matched pairs were analyzed. OS tended to be longer in the ablation group than in the nonablation group (not reached vs. 25.7 months and <i>p</i> = 0.090). PPS was significantly longer in the ablation group (37.7 vs. 9.17 months and <i>p</i> = 0.043). In multivariable analyses adjusted for ALBI score and tumor number, ablation showed a trend toward improved OS (HR 0.393 and <i>p</i> = 0.063) and was associated with prolonged PPS (HR 0.335 and <i>p</i> = 0.035), although residual confounding limits causal inference. Sensitivity analyses showed consistent results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In selected patients who initially achieved disease control with Atez/Bev, ablation at PD may be a potential salvage approach associated with prolonged PPS. These exploratory and hypothesis-generating findings warrant prospective validation of ablation-based salvage strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1161-1169"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873980","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":"Lenvatinib Promotes Metabolic Reprogramming Through RTK to Inhibit Hepatocellular Carcinoma Proliferation and Metastasis","authors":"Xiaofang Zhao,&nbsp;Shengxiang Yan,&nbsp;Jing Meng,&nbsp;Limin Wang","doi":"10.1111/hepr.70164","DOIUrl":"10.1111/hepr.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC), the third leading cause of cancer mortality, is targeted by Lenvatinib—a multi-receptor tyrosine kinase (RTK) inhibitor suppressing VEGFR/FGFR signaling. This study explored whether lenvatinib modulates the tumor metabolic microenvironment to inhibit HCC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we used bioinformatics approaches such as metabolic scoring, drug sensitivity analysis, and metabolic profiling, combined with in vitro and in vivo functional assays including CCK-8 proliferation assays, transwell invasion assays, and scratch wound healing assays to elucidate the novel mechanisms underlying the therapeutic effects of lenvatinib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified elevated metabolic pathway activity in HCC tumors, correlating with heightened lenvatinib sensitivity. Transcriptomic analysis revealed downregulation of PLA2G4E post-lenvatinib treatment, while metabolomics showed reduced choline and <i>ω</i>-3 arachidonic acid metabolites. High PLA2G4E expression predicted shorter recurrence-free (RFS) and disease-free survival (DFS). Functional assays demonstrated PLA2G4E's pro-tumor role through interaction with MAPK1/3 in the RAS/MAPK/ERK pathway. Lenvatinib suppressed MAPK1/3, PLA2G4E, and PDGF/PDGFR expression (validated by WB/qPCR/immunofluorescence), whereas MAPK inhibitors did not affect PDGF/PDGFR. Co-IP confirmed PLA2G4E-MAPK1/3 binding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings establish that lenvatinib inhibits HCC by regulating lipid metabolism through the PDGF/GFR-MAPK-PLA2G4E axis, expanding the mechanistic understanding of RTK inhibitors and proposing metabolic pathway–targeted combination therapies for HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1114-1126"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672842","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":"Correction to “The Nara Declaration: A New Collaborative Flow for Chronic Liver Disease Between Primary Care Physicians and Gastroenterologists/Hepatologists”","authors":"","doi":"10.1111/hepr.70168","DOIUrl":"10.1111/hepr.70168","url":null,"abstract":"<p>T. Kawaguchi, H. Yoshiji, S. Mochida, and T. Takehara, “The Nara Declaration: A New Collaborative Flow for Chronic Liver Disease Between Primary Care Physicians and Gastroenterologists/Hepatologists,” <i>Hepatology Research</i> 56, no. 1 (2026): 3–8, https://doi.org/10.1111/hepr.70065.</p><p>The following credit line should be added to the legend for Figure 1 and the description for the Graphical Abstract of the above article:</p><p>Figure 1 and the graphical abstract were created based on free materials provided by the Japan Society of Hepatology (Nara Declaration). https://www.jsh.or.jp/lib/files/medical/nara_sengen/kanren_gazou.pdf.</p><p>We apologize for this error.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrosis-4 Index as a Robust Long-Term Predictor of Cancers in Metabolic Dysfunction–Associated Steatotic Liver Disease","authors":"Ayumi Kanamoto,&nbsp;Teruki Miyake,&nbsp;Shinya Furukawa,&nbsp;Osamu Yoshida,&nbsp;Keiichiro Horiuchi,&nbsp;Yoshimasa Murakami,&nbsp;Masumi Miyazaki,&nbsp;Hironobu Nakaguchi,&nbsp;Ryo Yano,&nbsp;Yuki Okazaki,&nbsp;Sho Ishikawa,&nbsp;Yuki Numata,&nbsp;Atsushi Yukimoto,&nbsp;Yoshiko Nakamura,&nbsp;Mitsuhito Koizumi,&nbsp;Takao Watanabe,&nbsp;Yasunori Yamamoto,&nbsp;Yoshio Tokumoto,&nbsp;Masashi Hirooka,&nbsp;Masanori Abe,&nbsp;Yoichi Hiasa","doi":"10.1111/hepr.70159","DOIUrl":"10.1111/hepr.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We investigated whether the baseline fibrosis-4 (FIB-4) index stratifies long-term cancer risk in patients with biopsy-proven MASLD and compared its discrimination for HCC and extrahepatic malignancies against other noninvasive fibrosis markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this single-center retrospective cohort study, 417 adults with biopsy-proven MASLD (2001–2024) were followed for incident malignancy (median follow-up, 4.75 years). Patients were categorized using standard FIB-4 thresholds (&lt; 1.3, 1.3–2.67, ≥ 2.67). Cause-specific Cox models and Fine–Gray competing-risk models were used to estimate adjusted hazard ratios (HRs) for HCC and extrahepatic cancer. Discriminative performance was evaluated using Harrell's C-index and time-dependent area under the curve (AUC) values at 3, 5, and 10 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During followup, 24 patients (5.8%) developed HCC, whereas 40 (9.6%) developed extrahepatic cancer. The ≥ 2.67 category was associated with markedly increased risks of HCC (adjusted HR 35.31) and extrahepatic cancer (adjusted HR 13.10) compared with &lt; 1.3. Associations remained robust in competing-risk and age-adjusted sensitivity analyses. FIB-4 showed the highest and most consistent discriminative performance among the evaluated indices (C-indices of 0.83 for HCC and 0.78 for extrahepatic cancer). Time-dependent AUCs improved over time and exceeded 0.80 for HCC after 5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The FIB-4 index provides consistent long-term risk stratification for HCC and shows an association with extrahepatic cancer among commonly used noninvasive fibrosis markers. Its strong time-dependent discrimination for HCC and moderate discrimination for extrahepatic cancer support its potential role as a simple, widely accessible tool for long-term risk stratification in MASLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1079-1088"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473415","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":"Clinical Significance of Anti-Atezolizumab Antibodies in Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab","authors":"Keishi Ouchi,&nbsp;Jun Inoue,&nbsp;Masashi Ninomiya,&nbsp;Mio Tsuruoka,&nbsp;Kosuke Sato,&nbsp;Kotaro Doi,&nbsp;Kengo Watanabe,&nbsp;Tomoya Sasazaki,&nbsp;Atsushi Masamune","doi":"10.1111/hepr.70162","DOIUrl":"10.1111/hepr.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Systemic therapy is required for unresectable hepatocellular carcinoma (HCC). Atezolizumab plus bevacizumab (ATZ/BEV) is the recommended first-line treatment for HCC; however, the development of anti-drug antibodies (ADAs) against ATZ may impair its therapeutic efficacy. Although ADAs have been reported in other cancers treated with immune checkpoint inhibitors, the incidence and clinical relevance in HCC remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 50 patients with unresectable HCC who received ATZ/BEV between April 2020 and December 2024. Serum samples were obtained at baseline and after treatment initiation, primarily at the third cycle, and ATZ-ADA levels were measured using ELISA. Tumor response was assessed by modified RECIST, and survival was evaluated by the Kaplan–Meier method and Cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median ATZ-ADA levels after treatment initiation were higher in patients with progressive disease than in those with disease control (0.46 vs. 0.37, <i>p</i> = 0.02). Longitudinal analysis demonstrated a greater increase in ATZ-ADA levels from baseline in the progressive group (<i>p</i> = 0.04) than that in the other groups. ROC analysis identified a cutoff of 0.40 for predicting progression (AUC = 0.69), and 17 patients (34%) were classified as ATZ-ADA-positive (OD value ≥ 0.40). Progression-free survival (PFS) was significantly shorter in the ATZ-ADA-positive group than in the ATZ-ADA-negative group (3.8 vs. 9.4 months, HR = 2.24, <i>p</i> = 0.03), whereas no difference was observed in overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ATZ-ADAs were detected in 34% of patients with unresectable HCC and were associated with inferior PFS. ATZ-ADAs may serve as a promising biomarker for predicting treatment response and optimizing therapeutic strategies in HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1170-1176"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of HBV Genome Integration in Patients With HBV-Previously Infected NBNC-HCC","authors":"Tomoya Saito,&nbsp;Rigel Suzuki,&nbsp;Akhinur Rahman,&nbsp;Kento Mori,&nbsp;Samiul Alam Rajib,&nbsp;Nobuhiro Kobayashi,&nbsp;Yoichi Yamamoto,&nbsp;Sharmin Nahar Sithi,&nbsp;Takaya Ichikawa,&nbsp;Tatsuya Orimo,&nbsp;Tatsuhiko Kakisaka,&nbsp;Lihan Liang,&nbsp;Naganori Nao,&nbsp;Saori Suzuki,&nbsp;Tomokazu Tamura,&nbsp;Yorifumi Satou,&nbsp;Akinobu Taketomi,&nbsp;Takasuke Fukuhara","doi":"10.1111/hepr.70163","DOIUrl":"10.1111/hepr.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The incidence of non-B non-C hepatocellular carcinoma (NBNC-HCC), which is negative for Hepatitis B surface antigen and Hepatitis C virus antibodies, is on the rise. Relatively higher numbers of NBNC-HCC patients are Hepatitis B core antibody (HBcAb) positive, suggesting that previous HBV infection may play a role in NBNC-HCC development, though the exact mechanisms are unclear. This study aimed to investigate whether HBV genomes are integrated into the host genome of HBcAb-positive NBNC-HCC cases and how these integrations may contribute to cancer development and progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HBV detection PCR using HBV-specific primers on DNA extracted from HBcAb-positive NBNC-HCC tissue samples was performed. Positive samples were further examined for HBV integration sites using Viral DNA-Capture sequencing Approach. Additionally, Hepatitis B core–related antigen (HBcrAg) serum levels were measured to assess whether they could be predictive for HBV detection PCR results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 90 HBcAb-positive NBNC-HCC samples, HBV genome amplification was detected in 19 samples, and differences in HBcrAg status were observed according to HBV detection PCR results. Eighteen of these samples showed HBV integration. The HBV genome was integrated near the <i>TERT</i> gene in 7 samples, resulting in significantly increased <i>TERT</i> mRNA levels, in the <i>KMT2B</i> gene (3 samples), and downstream of the <i>LOC441666</i> gene (2 samples).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The integration sites we identified in our samples have been previously reported in HBV-related HCC, suggesting that HBV integration may also contribute to hepatocarcinogenesis in HBcAb-positive NBNC-HCC. Furthermore, HBcrAg could serve as a potential, noninvasive marker for detecting the HBV genome in these cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 7","pages":"1101-1113"},"PeriodicalIF":3.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511697","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}