Hepatology Research最新文献

{"title":"Differential Cardiometabolic Risk Profiles of Lean and Obese Metabolic Dysfunction-Associated Steatotic Liver Disease: A Longitudinal Health Checkup Cohort Study.","authors":"Hayato Kawamura, Kei Fujiwara, Ryo Sato, Takanori Suzuki, Kiyoto Narita, Kentaro Matsuura, Shunsuke Nojiri, Shigehiro Shiraki, Hiromi Kataoka","doi":"10.1111/hepr.70275","DOIUrl":"https://doi.org/10.1111/hepr.70275","url":null,"abstract":"<p><strong>Background: </strong>Lean metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized. Whether it represents a distinct entity or a phenotype within the MASLD spectrum remains unclear. We examined differences in risk factor contribution and metabolic trajectories.</p><p><strong>Methods: </strong>In a longitudinal health checkup cohort (2017-2025), we included individuals without hepatic steatosis at baseline and excluded those with alcohol intake at or above the MetALD threshold. Incident MASLD was classified at diagnosis as Obese or Lean MASLD based on obesity status (BMI/WC). Baseline risk factors were evaluated using time-to-event and competing-risk models with interaction testing. Longitudinal metabolic changes were assessed using logistic regression, and repeated trajectories were examined using linear mixed-effects models.</p><p><strong>Results: </strong>Among 13,624 participants, 1865 developed incident MASLD (Obese MASLD, n = 1469; Lean MASLD, n = 396). Male sex, baseline obesity, glycemic abnormality/diabetes, hypertension, hypertriglyceridemia, and higher baseline ALT were independently associated with incident MASLD. Interaction analyses showed a stronger contribution of male sex and weaker contributions of hypertension and low HDL-C in Lean MASLD. Longitudinal analyses showed Δtriglycerides and ΔALT were consistently associated with incident MASLD in both phenotypes, whereas ΔBMI showed a stronger association with Obese MASLD.</p><p><strong>Conclusions: </strong>Lean MASLD shared a broadly similar cardiometabolic risk structure with Obese MASLD, whereas the relative contribution of risk factors differed between phenotypes. Male sex showed a stronger association with Lean MASLD, whereas longitudinal changes in triglycerides and ALT were consistently associated with incident MASLD across both phenotypes. These findings provide exploratory evidence of phenotype-specific metabolic associations requiring validation before clinical application.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193172","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":"An Integrative Multi-Omic Biomarker Panel Distinguishes Hepatocellular Carcinoma From Chronic Liver Disease in HBV-Predominant Populations.","authors":"Hao Zhuang, Xiaopei Hao, Tingting Zhang, Deqiang Li, Guanghao Li, Zhongyi Li, Yuanlin Xu, Shuaiya Ma, Xiangjun Qian, Bo Meng, Xianzhou Zhang, Tiantian Zheng, Feng Han, Hao Wang, Yongmei Li, Nanmu Yang","doi":"10.1111/hepr.70274","DOIUrl":"https://doi.org/10.1111/hepr.70274","url":null,"abstract":"<p><strong>Aim: </strong>DNA methylation is a promising diagnostic biomarker for various cancers including hepatocellular carcinoma (HCC). We aimed to identify aberrant DNA methylation and protein alterations via integrated approaches and develop a highly predictive biomarker panel for blood-based discrimination of HCC from non-HCC chronic liver disease (CLD) in an HBV-predominant population.</p><p><strong>Methods: </strong>Genome-wide methylation profiling was conducted to screen hypermethylated CpG sites and genes distinguishing 55 HCC and matched non-HCC tissues. Candidate marker genes were then evaluated with five protein markers in 299 blood samples, and a diagnostic model was developed and validated in an independent cohort of 149 participants.</p><p><strong>Results: </strong>Methylation pattern analysis identified 44 candidate hypermethylation biomarkers using four strategies. Through cross-validation, a panel of six methylation markers from four different groups yielded an AUC of 0.938, surpassing other methylation marker panels. A logistic regression model incorporating four DNA methylation markers and two protein markers achieved sensitivities of 91.8% and 88.4% at specificities of 95.4% and 93.8% in the training and validation sets, respectively. The 6-marker panel showed higher sensitivity of 82.9% for BCLC 0-A HCC, outperforming alpha-fetoprotein (AFP), and des-gamma-carboxyprothrombin (DCP).</p><p><strong>Conclusions: </strong>The developed 6-marker model demonstrated strong diagnostic performance for distinguishing HCC from non-HCC CLD in the studied HBV-predominant cohorts. It outperformed AFP and DCP in this case-control setting and may have potential for blood-based HCC detection. Prospective validation in surveillance cohorts is required before clinical implementation.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206776","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":"Toward a Synthetic Data Revolution: Diffusion Model-Enhanced Hepatocellular Carcinoma Prediction in Steatotic Liver Disease","authors":"Masaya Sato,&nbsp;Takuma Nakatsuka,&nbsp;Yuki Matsushita,&nbsp;Takuma Kaneko,&nbsp;Keisuke Mabuchi,&nbsp;Tomoharu Yamada,&nbsp;Kazuya Okushin,&nbsp;Tatsuya Minami,&nbsp;Yotaro Kudo,&nbsp;Satoshi Kodera,&nbsp;Kazuhiko Koike,&nbsp;Mitsuhiro Fujishiro,&nbsp;Ryosuke Tateishi","doi":"10.1111/hepr.70213","DOIUrl":"10.1111/hepr.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Steatotic liver disease (SLD) encompasses a heterogeneous spectrum with varying risks of hepatocellular carcinoma (HCC). Limited sample sizes limit the development of predictive models, particularly for rare outcomes. This study evaluated whether generative artificial intelligence (AI)-based synthetic data augmentation can enhance HCC risk prediction in SLD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A random survival forest (RSF) model was developed using data from 406 patients with biopsy-confirmed SLD. The dataset was divided into training (<i>n</i> = 284) and testing (<i>n</i> = 122) cohorts. Two synthetic data generation approaches, the conditional tabular generative adversarial network (CTGAN; a type of generative adversarial network [GAN]) and diffusion models, augmented the training dataset from 284 to 1000 samples. Model performance was assessed using Harrell's C-index and integrated Brier score (IBS). Synthetic data quality was evaluated using maximum mean discrepancy (MMD) and Wasserstein distance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During the mean follow-up of 5.9 years, 12 (3.0%) patients developed HCC. In the test cohort, the baseline RSF model achieved a C-index of 0.912. Following augmentation, the diffusion-augmented model improved to 0.949, whereas the GAN-augmented model decreased to 0.818. Diffusion-generated data showed superior fidelity with a lower MMD (0.0303 vs. 0.0762) and Wasserstein distance (0.0467 vs. 0.1145) than GAN-generated data. Both augmentation approaches improved calibration (IBS: diffusion, 0.0103; GAN, 0.0108 vs. baseline, 0.0114).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Diffusion-based synthetic data augmentation improved HCC risk prediction in the test cohort, whereas GAN augmentation reduced model accuracy. These findings suggest that diffusion models may help address the data scarcity challenges in hepatology research, potentially providing a useful approach for developing predictive models in limited cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1466-1474"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149467","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":"Hepatic Carcinoma With Epithelial–Myoepithelial Differentiation and Metachronous Intrahepatic Recurrence Following Curative Resection: A Rare Case Report","authors":"Ryo Nagao,&nbsp;Tomoyuki Abe,&nbsp;Masateru Yamamoto,&nbsp;Yuki Imaoka,&nbsp;Naruhiko Honmyo,&nbsp;Seiichi Shimizu,&nbsp;Shintaro Kuroda,&nbsp;Hiroyuki Tahara,&nbsp;Masahiro Ohira,&nbsp;Kentaro Ide,&nbsp;Tsuyoshi Kobayashi,&nbsp;Tetsuya Nakagiri,&nbsp;Koji Arihiro,&nbsp;Hideki Ohdan","doi":"10.1111/hepr.70247","DOIUrl":"10.1111/hepr.70247","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>Epithelial-myoepithelial carcinoma (EMC), a malignant tumor with biphasic epithelial and myoepithelial differentiation, is typically a salivary gland neoplasm. Contrastingly, myoepithelial carcinoma (MEC) predominantly comprises myoepithelial cells. In salivary gland pathology, biphasic ductal tumors are classified as EMC, even with a predominant myoepithelial component. Primary hepatic tumors showing myoepithelial and epithelial–myoepithelial differentiation are rare, with uncertain definition and clinical behavior owing to limited reported hepatic carcinoma with MEC/EMC spectrum cases. Here, we report a unique case with intrahepatic recurrence that was successfully managed with repeat hepatectomies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>A 66-year-old woman presented with pain in the right hypochondrium. Imaging revealed a 13 cm tumor in the right hepatic lobe, and biopsy suggested squamous cell carcinoma. After portal vein embolization, right trisectionectomy was performed. Histopathology revealed a biphasic structure with duct-forming epithelial cells surrounded by myoepithelial cells, confirming hepatic carcinoma with epithelial–myoepithelial differentiation. After 2 years, multiple intrahepatic recurrences without extrahepatic disease were detected and repeat hepatectomies were performed. The patient remains recurrence-free 1 year post-reoperation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Hepatic carcinoma with epithelial–myoepithelial differentiation is rare, with uncertain definition and clinical behavior. Careful exclusion of extrahepatic primaries, detailed immunophenotyping, and long-term surveillance are essential. Repeat hepatectomies may be a curative option for intrahepatic recurrence in selected patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1556-1561"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535644","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":"Response to “Comment on ‘Anti-MRPS27 Antibody: A Novel Diagnostic Biomarker for Autoimmune Hepatitis Identified via a Human Proteome Microarray’”","authors":"Jun Wada,&nbsp;Kazumichi Abe,&nbsp;Hiromasa Ohira","doi":"10.1111/hepr.70214","DOIUrl":"10.1111/hepr.70214","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1562-1563"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198805","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":"Hepatologist-Driven Screening for Obstructive Sleep Apnea in Patients With MASLD Using a Modified STOP-Bang Questionnaire: The SOMA Model","authors":"Naruyasu Kakita,&nbsp;Shin Satake,&nbsp;Midori Jono,&nbsp;Hiroshi Tsumuro,&nbsp;Shuko Iwatani,&nbsp;Kenji Aoi,&nbsp;Masami Yamazaki,&nbsp;Toshio Naka,&nbsp;Kazuhiro Katayama","doi":"10.1111/hepr.70225","DOIUrl":"10.1111/hepr.70225","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the feasibility, diagnostic yield, and downstream clinical linkage of a hepatologist-driven obstructive sleep apnea (OSA) screening pathway using a modified STOP-Bang questionnaire in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From July 2025 to March 2026, 555 outpatients with MASLD were screened using the Screening for OSA in MASLD (SOMA) model. Home sleep apnea testing (HSAT) referral relied on the modified STOP-Bang questionnaire, Epworth Sleepiness Scale (ESS), and clinical judgment. Among 276 HSAT-evaluated patients, 258 with valid recordings were analyzed. Clinically significant OSA was defined as a respiratory event index (REI) ≥ 15 events/hour.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among HSAT-evaluated outpatients with MASLD, OSA (REI ≥ 5 events/hour) and clinically significant OSA occurred in 253 (98.1%) and 203 (78.7%), respectively. The modified STOP-Bang questionnaire outperformed the ESS (area under the curve: 0.616 vs. 0.485, <i>p</i> = 0.021). A modified STOP-Bang score ≥ 3 showed high sensitivity (93.6%) but low specificity (7.3%), whereas a score ≥ 5 showed more balanced sensitivity (59.1%) and specificity (54.5%). ESS score ≥ 11 showed poor sensitivity (10.8%). Among patients with REI ≥ 15 and ≥ 30 events/hour, full polysomnography was completed or scheduled in 64.0% and 73.0%, respectively. OSA severity was not significantly associated with Fibrosis-4 index, Mac-2 binding protein glycosylation isomer levels, or shear wave elastography findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Clinically significant OSA was frequent among selected HSAT-evaluated MASLD outpatients. The SOMA model may represent a feasible hepatologist-driven screening/referral pathway integrating structured triage, clinical judgment, and HSAT. However, these findings should not be interpreted as prevalence estimates or evidence of long-term clinical benefit.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1547-1555"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277139","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":"Hepatitis B Virus Infection Status in Japanese Children Prior to Universal Vaccination: Sustained Effectiveness of Mother-to-Child Transmission Prevention and Residual Infection Burden","authors":"Aiko Sakai,&nbsp;Yasuhito Tanaka,&nbsp;Hiroshi Yotsuyanagi,&nbsp;Masaya Sugiyama,&nbsp;Ichiro Morioka,&nbsp;Kiyotaka Kosugiyama,&nbsp;Kimiaki Uetake,&nbsp;Tomohiro Katsuta,&nbsp;Atsushi Imamura,&nbsp;Tomoko Takano,&nbsp;Hitoshi Tajiri,&nbsp;Akihito Ishida,&nbsp;Kosuke Ushijima,&nbsp;Yumiko Nakashima,&nbsp;Hiroyuki Moriuchi,&nbsp;Shinji Iwane,&nbsp;Kota Sawada,&nbsp;Yosuke Shimizu,&nbsp;Yukari Uemura,&nbsp;Manabu Tagawa,&nbsp;Masashi Mizokami,&nbsp;Ryo Sumazaki","doi":"10.1111/hepr.70212","DOIUrl":"10.1111/hepr.70212","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the effectiveness of prevention of mother-to-child transmission (PMTCT) over 25 years, we conducted a nationwide epidemiological survey through a comprehensive assessment of hepatitis B virus (HBV) markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two cohorts were recruited before universal vaccination: children aged 9–10 years undergoing school health checkups (Group 1) and hospital patients 0–15 years of age from 11 hospitals across Japan to assess age and regional differences (Group 2). Hepatitis B surface antigen (HBsAg) and core antibody (anti-HBc) were measured in both cohorts. HBV-DNA was tested to evaluate occult HBV infection and viral genotypes in Group 2. Anti-HBs antibody was measured to estimate HBV vaccine coverage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In Group 1 and Group 2, 8125 and 8453 samples were collected, respectively. HBsAg prevalence was 0% in Group 1 and 0.047% in Group 2 using a conventional assay (Lumipulse II HBsAg). Most HBsAg-positive samples were from children &lt; 4 years. HBsAg-negative and anti-HBc-positive samples were detected in 0.42% of Group 1 and 0.95% of Group 2. Among these samples in Group 2, 10.3% were HBV-DNA-positive, indicating occult HBV infection. Genotype C predominated; however, four genotype D cases were identified in Hokkaido. Anti-HBs positivity among HBV-uninfected samples at ages 1, 2, 5, 10, and 15 years was 53.4%, 27.5%, 7.5%, 5.6%, and 1.9%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Following the implementation of PMTCT measures in Japan, the prevalence of HBsAg-positive children was extremely low. However, the prevalence of occult infection and anti-HBc positivity indicated that some children remained exposed to HBV. To further eradicate HBV infection, universal vaccination was introduced nationwide in 2016.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1457-1465"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360572","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":"Metabolic Burden and Hyperuricemia Are Associated With CKD-Related Outcomes in Individuals With and Without Steatotic Liver Disease","authors":"Michihiro Iwaki,&nbsp;Hideki Fujii,&nbsp;Yoshihiro Kamada,&nbsp;Yuichiro Suzuki,&nbsp;Koji Sawada,&nbsp;Miwa Tatsuta,&nbsp;Tatsuji Maeshiro,&nbsp;Hiroshi Tobita,&nbsp;Tsubasa Tsutsumi,&nbsp;Takemi Akahane,&nbsp;Chitomi Hasebe,&nbsp;Miwa Kawanaka,&nbsp;Takaomi Kessoku,&nbsp;Yuichiro Eguchi,&nbsp;Hayashi Syokita,&nbsp;Masato Yoneda,&nbsp;Atsushi Nakajima,&nbsp;Tomoari Kamada,&nbsp;Hitoshi Yoshiji,&nbsp;Takumi Kawaguchi,&nbsp;Hiroshi Sakugawa,&nbsp;Asahiro Morishita,&nbsp;Tsutomu Masaki,&nbsp;Takumi Ohmura,&nbsp;Toshio Watanabe,&nbsp;Yoshioki Yoda,&nbsp;Nobuyuki Enomoto,&nbsp;Masafumi Ono,&nbsp;Kanako Fuyama,&nbsp;Kazufumi Okada,&nbsp;Naoki Nishimoto,&nbsp;Yoichi M. Ito,&nbsp;Hirokazu Takahashi,&nbsp;Yoshio Sumida,&nbsp;Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)","doi":"10.1111/hepr.70224","DOIUrl":"10.1111/hepr.70224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Although steatotic liver disease (SLD) has been associated with chronic kidney disease (CKD), it remains unclear whether CKD-related outcomes are driven by hepatic steatosis itself or by accompanying cardiometabolic abnormalities. We investigated the relative contribution of hepatic steatosis and cardiometabolic risk factors to CKD-related outcomes using a large Japanese health screening cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 30,648 SLD and 76,182 non-SLD participants enrolled in the MIRACLE-J cohort across 13 centers in Japan between 2014 and 2018 were analyzed. CKD-related outcomes were defined as reduced estimated glomerular filtration rate (eGFR&lt; 60 mL/min/1.73 m²) and proteinuria. Multivariable logistic regression and trend analyses were performed to identify factors associated with these outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with non-SLD participants, those with SLD exhibited a higher burden of cardiometabolic abnormalities. Type 2 diabetes mellitus, obesity, and hyperuricemia were independently associated with proteinuria, whereas advanced age (≥ 65 years), low alcohol intake, and hyperuricemia were strongly associated with reduced eGFR. After multivariable adjustment, SLD showed an inverse association with CKD-related outcomes. In both SLD and non-SLD populations, the prevalence of CKD-related outcomes increased stepwise with a higher number of cardiometabolic risk factors. Incorporation of hyperuricemia significantly improved model fit for reduced eGFR (Δ−2 log likelihood = 119.4, <i>p</i> &lt; 0.001) and modestly improved model fit for proteinuria (<i>p</i> = 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CKD-related outcomes were more strongly associated with the burden of cardiometabolic abnormalities than with hepatic steatosis itself, and these associations were consistent in individuals with and without SLD. Hyperuricemia provided incremental value for renal risk stratification within this cardiometabolic framework, underscoring the importance of comprehensive metabolic risk assessment beyond liver fat status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1535-1546"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761093","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":"Fragmentation Analysis of the MYC Enhancer in Cell-Free DNA by qPCR for Early Detection of Hepatocellular Carcinoma","authors":"Yan Jiang,&nbsp;Xuchu Wang,&nbsp;Yibei Dai,&nbsp;Pan Yu,&nbsp;Yue Cheng,&nbsp;Depeng Wang,&nbsp;Tao Chen","doi":"10.1111/hepr.70222","DOIUrl":"10.1111/hepr.70222","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The early detection of hepatocellular carcinoma (HCC) remains a significant challenge. This study aimed to develop a quantitative PCR (qPCR) assay to analyze the fragment size distribution of cfDNA at the enhancer region of the oncogene MYC, evaluate its potential ability as a diagnostic biomarker for HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective case-control study, we enrolled 40 patients with newly diagnosed HCC, 45 patients with cirrhosis, and 130 healthy volunteers. We designed two overlapping primer pairs to amplify a long (432 bp) and a short (65 bp) fragment via qPCR targeting MYC enhancer region. The Fragment Index (FI-myc), defined as the ratio of short to long fragment, was calculated to infer regional chromatin accessibility, and the diagnostic performance of FI-myc was evaluated using receiver operating characteristic (ROC) curve and logistic regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FI-myc levels were significantly elevated in HCC patients compared to those with cirrhosis and healthy controls (<i>p</i> &lt; 0.01). Using the cutoff of 1.87, FI-myc demonstrated a sensitivity of 85.02% for discriminating HCC from cirrhosis and healthy controls. The area under the ROC curve (AUC) for FI-myc was 0.81, which was significantly superior to that of alpha-fetoprotein (AFP) (AUC = 0.49, <i>p</i> &lt; 0.001). FI-myc maintained high sensitivity of 80.09% in early-stage HCC, and could detect 81.49% of HCC patients with negative AFP. Multivariate analysis demonstrated FI-myc as an independent indicator for HCC (OR = 2.82, <i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We developed a qPCR-based assay to infer MYC enhancer accessibility. The FI-myc index represents a promising liquid biopsy biomarker for early HCC detection, particularly as a complementary tool in AFP-negative cases, showing potential for clinical translation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1516-1523"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277178","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":"Low Alpha-Fetoprotein in Non-Viral Early-Stage Hepatocellular Carcinoma: Complementary Des-Gamma-Carboxyprothrombin","authors":"Yuji Ikeda,&nbsp;Shunsuke Sato,&nbsp;Rihwa Om,&nbsp;Masahiro Yamaguchi,&nbsp;Hiroki Nago,&nbsp;Yuichiro Terai,&nbsp;Yuji Kita,&nbsp;Sho Sato,&nbsp;Ayato Murata,&nbsp;Yuji Shimada,&nbsp;Keisuke Hamamura,&nbsp;Tatsuki Oyaizu,&nbsp;Takuya Genda","doi":"10.1111/hepr.70215","DOIUrl":"10.1111/hepr.70215","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>Alpha-fetoprotein (AFP) is widely used in hepatocellular carcinoma (HCC) surveillance, but its performance may vary with etiology and tumor stage. We assessed etiology-specific AFP and des-gamma-carboxyprothrombin (DCP) positivity at HCC diagnosis, focusing on early-stage disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively enrolled consecutive adults with newly diagnosed, treatment-naïve HCC at two tertiary centers in Japan (2007–2023). AFP (cutoff ≥ 10 ng/mL) and DCP (≥ 40 mAU/mL) at diagnosis were analyzed overall and by etiology (Hepatitis B virus (HBV), Hepatitis C virus (HCV), sustained virological response [SVR], and non-B/non-C [NBNC]). Early stage was defined as Barcelona Clinic Liver Cancer (BCLC) 0/A and Union for International Cancer Control tumor–node–metastasis (UICC) T1a.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1396 patients, 760 (54.4%) had BCLC 0/A and 278 (19.9%) had T1a tumors. AFP positivity differed by etiology in BCLC 0/A disease (HBV 50.0%, HCV 64.6%, SVR-related 39.0%, NBNC 39.7%; <i>p</i> &lt; 0.001), and in T1a tumors (48.1%, 60.3%, 39.0%, and 34.5%, respectively; <i>p</i> = 0.002). DCP (<i>n</i> = 1364) positivity in BCLC 0/A showed less variability (40.6%, 47.8%, 40.8%, and 58.4%, respectively; <i>p</i> = 0.005). Either-marker positivity in BCLC 0/A increased (64.1%, 80.0%, 59.2%, and 70.6%, respectively); the incremental yield from DCP alone among AFP-negative cases was 21.1% in SVR-related and 30.5% in NBNC early-stage HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AFP positivity at diagnosis was substantially lower in early-stage SVR-related and NBNC HCC than in HCV-related HCC. Adding DCP provides complementary detection, supporting an etiology-aware dual-marker strategy at diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"56 10","pages":"1475-1483"},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175783","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}