Hepatology Research最新文献

{"title":"Dendritic Cell-Depleted Mice Develop the Autoimmune Biliary Disease That Serologically and Pathogenically Models Human Primary Biliary Cholangitis.","authors":"Jiaqi Zhang, Ryo Nakagawa, Qingpeng Xu, Ke Hu, Lin Ru, Hayato Nakagawa, Yoshihiro Hirata","doi":"10.1111/hepr.70014","DOIUrl":"https://doi.org/10.1111/hepr.70014","url":null,"abstract":"<p><strong>Aim: </strong>Primary biliary cholangitis (PBC) is an autoimmune liver disease marked by progressive bile duct damage, leading to bile retention. Dendritic cells (DCs), as antigen-presenting cells, are crucial for immune regulation, and their dysfunction is linked to autoimmunity. This study demonstrates that DC-depleted mice manifest an autoimmune biliary disease resembling human PBC and investigates its mechanism.</p><p><strong>Methods: </strong>DC-depleted mice were generated by crossbreeding CD11c-Cre and Rosa26-DTA (ID) mice. Hepatobiliary changes were assessed using hematoxylin and eosin staining, serum biochemistry, flow cytometry, and immunohistochemistry. Liver gene expression was analyzed using quantitative polymerase chain reaction (qPCR) and RNA sequencing. Antimitochondrial antibody (AMA) and IFN-γ secretion were measured through enzyme-linked immunosorbent assay. Wild-type mice were intraperitoneally injected with serum from control mice (IP-Ctrl) or ID mice (IP-ID); in some experiments, anti-PDCE-2-depleted ID serum (IP-ΔPDCE2) was used.</p><p><strong>Results: </strong>ID mice showed significant portal inflammation, with neutrophils and CD4⁺ T/CD8⁺ T lymphocytes around bile ducts. Serum AMA levels in ID mice were 1.8-fold higher than those of control mice. qPCR revealed higher expression of inflammatory molecules and cytokines (TNF-α, IFN-γ, IL-2, IL-12p35, and N-ras) in the liver of ID mice. IP-ID mice developed cholangitis within 10 days, marked by CD4⁺ T-cell-dominant infiltration, which was attenuated by depleting anti-PDCE-2 antibodies from ID serum.</p><p><strong>Conclusions: </strong>DC depletion induces PBC-like serological and histological features, implicating DC dysfunction in immune dysregulation through CD4⁺ T-cell activation and anti-PDCE-2 antibody production. Our ID and IP models show that both T-cell responses and autoantibodies are essential contributors to PBC pathogenesis.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788911","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":"Oncologic impact of statin use on patients treated with hepatectomy for intrahepatic cholangiocarcinoma.","authors":"Jae Hwan Jeong, Dai Hoon Han, Gi Hong Choi, Kyung Sik Kim, Jin Sub Choi, Sung Hyun Kim, Sangheun Lee","doi":"10.1111/hepr.14205","DOIUrl":"10.1111/hepr.14205","url":null,"abstract":"<p><strong>Aim: </strong>Currently, the only recognized curative treatment for intrahepatic cholangiocarcinoma (ICC) is surgical resection. However, the impact of various clinical factors, including patient history and pharmacological interventions, on survival outcomes is still not fully understood. We aimed to bridge this knowledge gap by identifying clinical determinants that may influence the prognosis of ICC after surgical resection.</p><p><strong>Methods: </strong>We conducted a study on 172 patients who underwent hepatectomy for ICC between 2010 and 2019. We evaluated patient demographics, tumor characteristics, and whether patients were on statin therapy. Kaplan-Meier methods were used to analyze overall survival (OS) and recurrence-free survival (RFS), whereas multivariate analysis was utilized to identify prognostic factors.</p><p><strong>Results: </strong>Statin use was associated with significantly improved OS and RFS. The mean OS was 90.5 months in the statin group compared to 59.9 months in the statin-naive group (p = 0.001). Similarly, RFS was longer in the statin group (77.3 vs. 48.1 months; p = 0.006). Subgroup analyses demonstrated consistent benefits of statin use across different age groups and genders. Multivariate analysis identified statin use as an independent prognostic factor for OS (HR: 0.49, 95% CI: 0.29-0.82, p = 0.007) and RFS (HR: 0.60, 95% CI: 0.36-0.98, p = 0.043).</p><p><strong>Conclusions: </strong>Statin therapy may be a potentially favorable medication for patients undergoing hepatectomy for ICC. However, further evaluation of its clinical benefits is required, and additional studies are recommended.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":"1139-1148"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019107","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":"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":"1149-1158"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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":"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":"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":"1111-1127"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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":"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":"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":"1159-1171"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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":"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":"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":"1193-1203"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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":"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":"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":"1184-1192"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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":"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":"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":"1172-1183"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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}

{"title":"Predicting the risk of developing diabetes in steatotic liver disease using controlled attenuation parameter in a health checkup population.","authors":"Takuma Nakatsuka, Yutaka Yamaji, Ryosuke Tateishi, Takako Ogasawara, Rena Mihara, Yoshiaki Kawashima, Tetsuharu Ono, Tomoharu Yamada, Tatsuya Minami, Masaya Sato, Takeshi Hayashi, Yuki Matsushita, Kazuyoshi Funato, Tatsuya Sato, Tomotaka Saito, Yotaro Kudo, Hirofumi Kogure, Hayato Nakagawa, Yoshinari Asaoka, Yasuo Tanaka, Yousuke Nakai, Hideaki Ijichi, Mitsuhiro Fujishiro","doi":"10.1111/hepr.14216","DOIUrl":"10.1111/hepr.14216","url":null,"abstract":"<p><strong>Introduction: </strong>Excessive hepatic steatosis is linked to systemic metabolic disorders. We investigated the association between hepatic steatosis quantified by controlled attenuation parameter (CAP) and the development of type 2 diabetes mellitus (T2DM) in a health checkup population.</p><p><strong>Methods: </strong>The present retrospective cohort study included 1636 participants without T2DM who underwent CAP measurement and were followed up at annual health checkups. Cox proportional hazards regression was used to identify risk factors for T2DM development.</p><p><strong>Results: </strong>During a mean follow-up of 3.2 years, 181 participants developed T2DM. The cumulative incidence rates of T2DM were significantly higher in participants with severe steatosis (CAP ≥ 280 dB/m) compared with those without (13.9% vs. 4.8% at 3 years, p < 0.001). Multivariate analysis identified CAP as an independent predictor of new-onset T2DM (adjusted hazard ratio [aHR], 1.04 per 10 dB/m increase; 95% confidence interval [CI], 1.01-1.08, p = 0.01), along with fasting plasma glucose (aHR, 2.13 per 10 mg/dL; 95% CI, 1.77-2.55, p < 0.001), HbA1c (aHR, 1.25 per 0.1% increase; 95% CI, 1.19-1.32, p < 0.001), and platelet count (aHR, 0.95 per 10⁴/μL increase; 95% CI, 0.92-0.98, p = 0.001). A dose-response relationship was observed between CAP level and T2DM risk. In addition, suspected compensated advanced chronic liver disease (liver stiffness ≥10 kPa) and at-risk steatohepatitis (FibroScan-AST score ≥0.67) were associated with a higher incidence of T2DM (p < 0.001 for both).</p><p><strong>Conclusion: </strong>CAP quantification of hepatic steatosis effectively stratifies the risk of developing T2DM, facilitating timely intervention and prevention strategies.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":"1101-1110"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186952","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":"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":"1128-1138"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","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}