Hepatology Research最新文献

{"title":"Prognostic Value of PALBI in Patients With Hepatocellular Carcinoma and Concurrent Chronic Kidney Disease: A Nomogram Development","authors":"Jihye Lim,&nbsp;Seok–Hwan Kim,&nbsp;Myeong Jun Song","doi":"10.1111/hepr.70191","DOIUrl":"10.1111/hepr.70191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Prognosis in hepatocellular carcinoma (HCC) depends not only on tumor burden but also on liver function and comorbidities, particularly chronic kidney disease (CKD). Although several prognostic models exist, their performance in patients with HCC and CKD has not been systematically evaluated. This study compared the predictive accuracy of liver-specific models and developed a nomogram for individualized survival prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a nationwide multicenter cohort study of 1201 treatment–naive patients newly diagnosed with HCC and concurrent CKD. Prognostic performance for overall survival was assessed for Child–Pugh, MELD, MELD-Na, MELD 3.0, ALBI, and PALBI scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age was 70.4 ± 10.7 years, and 72.6% were male. Over a mean follow-up of 37.8 months, 1017 deaths occurred with an incidence rate of 269.1 per 1000 person–years. Among prognostic models, PALBI showed favorable discriminative ability with area under the receiver operating characteristic curve values of 0.871, 0.857, and 0.833 at 3, 6, and 12 months, respectively. Concordance index values were generally comparable among the models, with the PALBI-based model demonstrating consistent and reliable performance across most clinical subgroups. A nomogram incorporating age, AFP, CKD stage, BCLC stage, treatment modality, and PALBI grade provided individualized survival estimates with good calibration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with HCC and CKD, PALBI showed comparable prognostic performance to other liver-specific models, while maintaining clinical applicability based exclusively on objective laboratory parameters. The proposed nomogram, integrating PALBI with clinical and tumor factors, may serve as a practical tool to support personalized risk stratification and treatment decision-making in this complex population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1307-1318"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769830","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":"A Novel Diagnostic Approach for Hepatocellular Carcinoma Using Glycosylated Ferritin","authors":"Akiyo Ishiguro,&nbsp;Yutaka Suehiro,&nbsp;Issei Saeki,&nbsp;Maho Egusa,&nbsp;Norikazu Tanabe,&nbsp;Toshihiko Matsumoto,&nbsp;Tsuyoshi Ishikawa,&nbsp;Yuki Kunimune,&nbsp;Toshihiko Kobayashi,&nbsp;Mitsuaki Nishioka,&nbsp;Taro Takami,&nbsp;Takahiro Yamasaki","doi":"10.1111/hepr.70195","DOIUrl":"10.1111/hepr.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>With the increasing incidence of nonviral hepatocellular carcinoma (HCC), current surveillance markers such as alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP) show limitations. We investigated the percentage of glycosylated ferritin relative to total ferritin (%GF) as a novel diagnostic biomarker for HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Samples from 660 patients (chronic liver disease [CLD], <i>n</i> = 278 and HCC, <i>n</i> = 382) were divided into training and validation cohorts (7:3). Glycosylated ferritin was measured using concanavalin A, and %GF was calculated as 100 × (glycosylated ferritin/total ferritin). A multivariate logistic regression analysis was carried out in the training cohort and validated in the validation cohort to improve diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In all HCC stages, %GF levels were significantly lower than CLD. The sensitivity and specificity of %GF were 73.7% and 70.8%, respectively, in the training cohort, and 74.1% and 69.8%, respectively, in the validation cohort. The area under the curve (AUC) values of 0.782 (training) and 0.800 (validation) were comparable to those of AFP and DCP. We developed the GFAD index, integrating age, sex, %GF, AFP, and DCP. The GFAD index showed superior diagnostic performance with AUCs of 0.939 (training) and 0.923 (validation). The sensitivity and specificity were 81.9% and 92.7%, respectively (training), and 78.6% and 87.2%, respectively (validation). For early stage HCC, the sensitivity was 67.0% (training) and 69.2% (validation), regardless of the etiology of HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The diagnostic performance of %GF for HCC was comparable to AFP and DCP. Moreover, the GFAD index showed excellent performance, even in early stage HCC, regardless of etiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1319-1330"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814581","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":"Letter to the Editor: “Surgical Resections for Hepatocellular Carcinomas Arising From Fontan-Associated Liver Disease; Open, Laparoscopic and Robotic Hepatectomies”","authors":"Linfeng Sun,&nbsp;Wei Shao","doi":"10.1111/hepr.70192","DOIUrl":"10.1111/hepr.70192","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1436-1437"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837404","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":"Widespread Muscle Loss in Autoimmune Hepatitis and Its Adverse Prognostic Impact","authors":"Tomoko Tadokoro,&nbsp;Asahiro Morishita,&nbsp;Takushi Manabe,&nbsp;Hiroki Tai,&nbsp;Rie Yano,&nbsp;Mai Nakahara,&nbsp;Kyoko Oura,&nbsp;Koji Fujita,&nbsp;Shima Mimura,&nbsp;Joji Tani,&nbsp;Hideki Kobara","doi":"10.1111/hepr.70203","DOIUrl":"10.1111/hepr.70203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Reports on the prevalence of sarcopenia in patients with autoimmune hepatitis (AIH) are limited, and its association with prognosis remains unclear. Therefore, we evaluated sarcopenia-related factors and their prognostic impact associated with AIH and compared these findings with those of patients with primary biliary cholangitis (PBC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 161 patients with AIH or PBC who were followed up at our institution and underwent computed tomography (CT) between January 2004 and February 2025. Data on sex, age, comorbidities, sarcopenia-related factors, treatment, cirrhosis, and clinical outcomes were reviewed. Patients with the PBC–AIH overlap syndrome or concomitant malignancy were excluded. Sarcopenia was assessed using the psoas muscle mass index (PMI) on CT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 67 and 94 patients had AIH and PBC, respectively. The two groups showed no significant differences in the proportion of males, 5-year survival, or the prevalence of cirrhosis at diagnosis and other autoimmune diseases. A low PMI was observed in 32.8% and 17.0% of patients with AIH and PBC, respectively, and was significantly more frequent in patients with AIH (<i>p</i> = 0.02). Among patients with AIH, those with a low PMI had significantly poorer survival than those without it. Factors associated with poor prognosis in patients with AIH included a higher model for the end-stage liver disease (MELD) score, low PMI, and the presence of cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CT-based assessment of PMI in patients with AIH may provide supplementary prognostic information for risk stratification at diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1366-1373"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856235","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":"Diagnostic Impact of Two-Dimensional Shear Wave Elastography for Liver Fibrosis: A Multicenter Retrospective Study","authors":"Takashi Nishimura,&nbsp;Toshifumi Tada,&nbsp;Yasuaki Suzuki,&nbsp;Kento Imajo,&nbsp;Katsutoshi Sugimoto,&nbsp;Sadanobu Ogawa,&nbsp;Hidenori Toyoda,&nbsp;Tamami Abe,&nbsp;Hidekatsu Kuroda,&nbsp;Masashi Hirooka,&nbsp;Asako Nogami,&nbsp;Satoshi Oeda,&nbsp;Hirokazu Takahashi,&nbsp;Tomoyuki Akita,&nbsp;Reiichiro Kondo,&nbsp;Takuma Nakatsuka,&nbsp;Ryosuke Tateishi,&nbsp;Yoichi Hiasa,&nbsp;Yuichiro Eguchi,&nbsp;Atsushi Nakajima,&nbsp;Hirohisa Yano,&nbsp;Shigehiro Kokubu,&nbsp;Junko Tanaka,&nbsp;Fuminori Moriyasu,&nbsp;Masayoshi Kage,&nbsp;Takashi Kumada,&nbsp;Hiroko Iijima","doi":"10.1111/hepr.70194","DOIUrl":"10.1111/hepr.70194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Two-dimensional shear wave elastography (2D-SWE) is a non-invasive technique for assessing liver fibrosis. However, its clinical utility has not been fully established. This study evaluated the diagnostic accuracy of 2D-SWE using magnetic resonance elastography (MRE) as the reference standard in a retrospective, multicenter, large-scale cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 744 patients with chronic liver disease were included in the analysis. The association between 2D-SWE measurements and fibrosis stages determined by MRE was assessed. The correlation between 2D-SWE and MRE values was analyzed, and the diagnostic performance of 2D-SWE was evaluated using receiver operating characteristic (ROC) curve analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As 2D-SWE and MRE values were not normally distributed, they were log-transformed (Log-2D-SWE and Log-MRE) for analysis. A strong correlation was observed between Log-2D-SWE and Log-MRE values, with a correlation coefficient of 0.764 (<i>p</i> &lt; 0.001). When 2D-SWE values were stratified according to the histological stages of liver fibrosis (F0–F4), based on MRE data, the corresponding median values were 4.61, 5.63, 6.18, 7.44, and 11.64 kPa, respectively (<i>p</i> &lt; 0.001, Jonckheere–Terpstra test). The areas under the ROC curve (AUROCs) and cutoff values for 2D-SWE were 0.872 and 5.47 kPa for ≥ F1 (<i>n</i> = 285), 0.894 and 5.88 kPa for ≥ F2 (<i>n</i> = 217), 0.931 and 6.48 kPa for ≥ F3 (<i>n</i> = 137), and 0.937 and 7.39 kPa for F4 (<i>n</i> = 81), respectively. In subgroup analyses, AUROCs for detecting ≥ F2, ≥F3, and F4 exceeded 0.78, even among patients with elevated body mass index or advanced hepatic steatosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>2D-SWE represents a highly useful and reliable non-invasive modality for assessing of liver fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1331-1341"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814608","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":"Immunotherapy-Facilitated Conversion Surgery for Biliary Tract Cancer: A Case Series of Long-Term Survivors Following Durvalumab Combined With Gemcitabine and Cisplatin","authors":"Shinichiro Hasegawa,&nbsp;Hiroshi Wada,&nbsp;Ryoji Takada,&nbsp;Masahiko Kubo,&nbsp;Masahiro Umezu,&nbsp;Shigenori Nagata,&nbsp;Keiichiro Honma,&nbsp;Yasunari Fukuda,&nbsp;Hisateru Komatsu,&nbsp;Kunihito Gotoh,&nbsp;Kei Yamamoto,&nbsp;Ryota Mori,&nbsp;Masatoshi Kitakaze,&nbsp;Norihiro Matsuura,&nbsp;Yasunori Masuike,&nbsp;Takahito Sugase,&nbsp;Yuki Ushimaru,&nbsp;Masaaki Miyo,&nbsp;Yoshitomo Yanagimoto,&nbsp;Takashi Kanemura,&nbsp;Toshinori Sueda,&nbsp;Yoshinori Kagawa,&nbsp;Kazuyoshi Yamamoto,&nbsp;Junichi Nishimura,&nbsp;Hiroshi Miyata,&nbsp;Masayuki Ohue,&nbsp;Shogo Kobayashi","doi":"10.1111/hepr.70210","DOIUrl":"10.1111/hepr.70210","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Conversion surgery after systemic therapy is gaining attention in biliary tract cancer (BTC), yet evidence under gemcitabine, cisplatin, and durvalumab (GCD) remains scarce.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>We report three patients with initially unresectable BTC (two gallbladder cancers and one intrahepatic cholangiocarcinoma) who underwent curative surgery following GCD therapy. All patients received six to eight cycles of GCD, achieving significant tumor control. Radiologic responses included tumor regression, nodal clearance, and vascular detachment. Surgery consisted of extended hepatectomy or cholecystectomy with bile duct resection. All patients achieved R0 resection. One patient developed severe postoperative complications requiring intensive care unit (ICU) management; however, the patient recovered with appropriate treatment, whereas the remaining patients had no major postoperative complications. All patients remain recurrence-free 14–23 months postoperatively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GCD therapy may enable conversion surgery even in advanced BTC with limited metastases. Durable disease control, rather than maximal shrinkage, appears critical for resectability. This case series suggests that immunotherapy-integrated regimens can expand surgical opportunities and improve long-term outcomes in selected patients. Further studies are needed to optimize patient selection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1426-1435"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217638","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":"FOXS1 Promotes Liver Fibrosis Through TGF-β1/Smad Signaling: Targeting a Novel miR-212-5p/FTO Axis","authors":"Maoqun Zhu,&nbsp;Tong Zhang,&nbsp;Xiang Wang,&nbsp;Benshun Hu,&nbsp;Bingyi Dai,&nbsp;Baoyang Luo,&nbsp;Xinyi Xu,&nbsp;Donglin Sun,&nbsp;Xiaodong Xu","doi":"10.1111/hepr.70208","DOIUrl":"10.1111/hepr.70208","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Liver fibrosis is a progressive pathological condition characterized by excessive extracellular matrix (ECM) deposition, primarily driven by hepatic stellate cell (HSC) activation. Although Forkhead box S1 (FOXS1) has been implicated in fibrotic and neoplastic processes, its functional role in hepatic fibrosis and its regulatory mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>FOXS1 expression was analyzed in human fibrotic liver tissues, CCl₄-induced, and methionine-choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH) mouse models and activated HSCs. CCl₄-induced and MCD mouse models of liver fibrosis and TGF-β1-stimulated LX-2 and HSC-T6 cells and H-HSCs and M-HSCs were used to investigate FOXS1 function in vivo and in vitro. TGF-β1-induced fibrosis models were used to explore the FOXS1-TGF-β1/Smad axis in HSC activation. Furthermore, functional assays, luciferase reporter, RNA pulldown, MeRIP, and RIP assays were conducted to elucidate the regulatory relationships among FOXS1, miR-212-5p, and m6A demethylase FTO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FOXS1 expression was elevated in fibrotic human and mouse liver tissues and positively correlated with fibrosis severity. FOXS1 knockdown in mice ameliorated fibrosis, reduced ECM protein expression, and improved liver function. In HSCs, FOXS1 enhanced TGF-β1/Smad2/3 signaling in a positive feedback loop, promoting HSC activation, migration, and resistance to apoptosis. Mechanistically, miR-212-5p directly targeted FOXS1 and suppressed fibrogenesis, but its maturation was inhibited by FTO-mediated m6A demethylation of pri-miR-212. Additionally, FTO knockdown promoted miR-212-5p processing, downregulated FOXS1, and disrupted the TGF-β1/Smad loop, thereby exerting antifibrotic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FOXS1 acts as a novel driver of hepatic fibrosis that promotes HSC activation through TGF-β1/Smad-dependent feedback loop involving FTO-mediated m6A modification and miR-212-5p. Targeting the FTO/miR-212-5p/FOXS1 axis offers a promising therapeutic strategy for liver fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1402-1418"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162958","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":"Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma","authors":"Yuya Miura,&nbsp;Ryo Ashida,&nbsp;Keiichi Ohshima,&nbsp;Yukiyasu Okamura,&nbsp;Takeshi Nagashima,&nbsp;Keiichi Hatakeyama,&nbsp;Teiichi Sugiura,&nbsp;Katsuhisa Ohgi,&nbsp;Shimpei Otsuka,&nbsp;Hideyuki Dei,&nbsp;Yuko Kakuda,&nbsp;Takuma Oishi,&nbsp;Kenichi Urakami,&nbsp;Yasuto Akiyama,&nbsp;Katsuhiko Uesaka,&nbsp;Ken Yamaguchi","doi":"10.1111/hepr.70204","DOIUrl":"10.1111/hepr.70204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In hepatocellular carcinoma (HCC), intrahepatic recurrence includes true recurrence from clonal relapse and multicentric recurrence from de novo tumorigenesis. Recurrence timing is used to distinguish these types; however, its accuracy remains unclear. This study aimed to classify recurrent tumors based on somatic mutational concordance and assess the validity of recurrence timing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-exome sequencing was performed on paired primary and recurrent HCC tumors from 49 patients enrolled in a prospective institutional omics project. Tumors with ≥ 10 shared somatic mutations were classified as true recurrence. Clinicopathological features, recurrence timing, driver mutation patterns, and survival outcomes were compared between recurrence types. Mutational concordance was quantified using shared variant counts and the Jaccard similarity index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 49 patients, 22 (44.9%) showed true recurrence and 27 (55.1%) had multicentric recurrence. Multicentric recurrence tumors harbored no shared variants or only a single shared variant with the primary tumor. True recurrence was associated with significantly higher concordance in histological differentiation and Edmondson–Steiner grading and greater retention of <i>CTNNB1</i>, <i>TP53</i>, <i>ARID1A</i>, and <i>KEAP1</i> mutations. The number of shared variants (median: 115 vs. 0, and <i>p</i> &lt; 0.001) and the Jaccard index (median: 0.44 vs. 0.00 and <i>p</i> &lt; 0.001) were significantly higher in the true recurrence group. Recurrence timing was inconsistently correlated with mutational concordance, although a 3-year cutoff yielded significant separation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Recurrence timing alone insufficiently reflects clonal relationships. Genomic profiling offers a reliable framework for distinguishing between recurrence types and guiding HCC management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 9","pages":"1374-1381"},"PeriodicalIF":3.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928940","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":"Validation of the Baveno Endoscopy Avoidance Criteria in Japanese Patients With Chronic Liver Disease: A Real-World Cohort Study.","authors":"Maiko Asami, Yoshihito Uchida, Shohei Tsuji, Satsuki Ando, Kayoko Sugawara, Masamitsu Nakao, Nobuaki Nakayama, Yukinori Imai, Suguru Mizuno, Satoshi Mochida","doi":"10.1111/hepr.70263","DOIUrl":"https://doi.org/10.1111/hepr.70263","url":null,"abstract":"<p><strong>Background: </strong>The Baveno endoscopy avoidance criteria are widely used to reduce unnecessary screening endoscopy in patients with chronic liver disease. However, evidence regarding their performance in Japanese populations remains limited, and detection-oriented strategies for high-risk varices (HRV) may also be clinically relevant in settings with broad endoscopic availability.</p><p><strong>Methods: </strong>We retrospectively analyzed 1675 Japanese patients with chronic liver disease who underwent liver stiffness measurement (LSM) and upper gastrointestinal endoscopy at a single center. The performance and safety of the Baveno criteria were evaluated overall and by etiology. Patients were temporally divided into derivation and validation cohorts. Based on independent predictors of HRV, a simple high-risk varices detection score (HRV-DS) incorporating LSM, platelet count, and alcohol-related etiology was developed.</p><p><strong>Results: </strong>The Baveno criteria classified 79.4% of patients as suitable for endoscopy avoidance, with an overall HRV miss rate of 0.39%. However, safety was modestly reduced in patients with alcohol-related liver disease. The HRV-DS achieved 100% sensitivity for HRV detection at the lowest threshold (score ≥ 1), while recommending endoscopy to 27.0% of patients. At a higher threshold (score ≥ 2), sensitivity remained approximately 87% with improved positive predictive value. These findings were consistently reproduced in both derivation and validation cohorts.</p><p><strong>Conclusions: </strong>In this large real-world Japanese cohort, the Baveno endoscopy avoidance criteria demonstrated excellent safety for excluding HRV. The exploratory HRV-DS also showed high sensitivity for identifying HRV and may provide a complementary detection-oriented approach in clinical practice.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839514","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":"Nuclear Pan-Lysine Lactylation Immunoreactivity Is Associated With Poor Prognosis in Intrahepatic Cholangiocarcinoma.","authors":"Hitoshi Iwasaki, Shinji Itoh, Takuma Ishikawa, Yoshiyuki Kitamura, Mingyang Yu, Junya Mita, Norifumi Iseda, Kyohei Yugawa, Shohei Yoshiya, Takashi Motomura, Takeo Toshima, Takuro Isoda, Mototsugu Shimokawa, Shinichi Aishima, Kousei Ishigami, Yoshinao Oda, Tomoharu Yoshizumi","doi":"10.1111/hepr.70265","DOIUrl":"https://doi.org/10.1111/hepr.70265","url":null,"abstract":"<p><strong>Aim: </strong>Lysine lactylation (Kla) links cellular metabolism to gene regulation, but its significance in intrahepatic cholangiocarcinoma (ICC) remains unclear.</p><p><strong>Methods: </strong>Nuclear pan-Kla immunoreactivity was evaluated in 118 patients who underwent curative-intent resection for ICC. Associations with clinicopathological features, overall survival (OS), recurrence-free survival (RFS), and FDG-PET-derived SUVmax were analyzed. Functional assays and bulk RNA sequencing were performed in cholangiocarcinoma cells treated with lactate, the p300 inhibitor A-485, or the LDH inhibitor oxamate.</p><p><strong>Results: </strong>High nuclear pan-Kla immunoreactivity was associated with microscopic intrahepatic metastasis and poorer OS and RFS, and remained independently associated with both outcomes after multivariable adjustment. Adding Kla modestly increased the optimism-corrected C-index for OS, whereas RFS discrimination was not improved. Lactate increased pan-Kla signals but produced minimal phenotypic and transcriptional changes. In contrast, p300 or LDH inhibition reduced pan-Kla signals and was accompanied by reduced cell viability, colony formation, and wound closure; however, these effects cannot be attributed specifically to reduced Kla because A-485 and oxamate are not Kla-specific. RNA sequencing showed suppression of E2F target and G2M checkpoint programs. In an exploratory PET subgroup, the Kla H-score correlated weakly with SUVmax, and patients with high Kla and high SUVmax had the poorest outcomes.</p><p><strong>Conclusions: </strong>Nuclear pan-Kla immunoreactivity was independently associated with poor postoperative outcomes in resected ICC. Pharmacological modulation of lactylation-related pathways was accompanied by suppression of proliferative and cell cycle-related programs, although Kla-specific causality remains to be established.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840234","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}