Journal of Gastroenterology最新文献

{"title":"Usefulness of serum HBV RNA levels for predicting antiviral response to entecavir treatment in patients with chronic hepatitis B.","authors":"Masanari Kosaka, Hatsue Fujino, Masataka Tsuge, Kenji Yamaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Atsushi Ono, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Clair Nelson Hayes, Seiya Kashiyama, Sho Mokuda, Shinichi Yamazaki, Shiro Oka","doi":"10.1007/s00535-025-02211-5","DOIUrl":"10.1007/s00535-025-02211-5","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) RNA is an important serum biomarker of hepatic covalently closed circular DNA (cccDNA) transcriptional activity; however, its clinical characteristics remain unclear. This study evaluated the clinical utility of HBV RNA levels in patients with chronic hepatitis B (CHB).</p><p><strong>Methods: </strong>We studied 87 CHB patients with serum HBV DNA levels ≥ 5.0 log IU/mL who initiated entecavir (ETV) treatment between 2000 and 2018. Serum HBV RNA levels were measured at three-time points: before ETV treatment, at 12 weeks, and at 48 weeks after starting ETV treatment. Clinical markers associated with the antiviral effects of ETV treatment were analyzed.</p><p><strong>Results: </strong>Serum HBV RNA levels decreased in both HBeAg-positive and -negative patients during the observation period. In HBeAg-positive patients, multivariable analysis showed that lower HBV RNA levels at 48 weeks of ETV treatment were independently associated with HBeAg seroconversion. Additionally, lower baseline HBV RNA levels significantly predicted virologic response in those patients. In contrast, among HBeAg-negative patients, lower HBV core-related antigen (HBcrAg) levels and the FIB-4 index were independently associated with virologic response. In HBeAg-positive patients, those with higher baseline HBV RNA levels showed a more significant reduction in hepatitis B surface antigen levels.</p><p><strong>Conclusion: </strong>Serum HBV RNA levels predicted HBeAg seroconversion and early HBV DNA reduction in HBeAg-positive patients, while HBcrAg was significantly associated with virologic response in HBeAg-negative patients. These findings highlight the different predictive roles of HBV RNA and HBcrAg based on HBeAg status, which may provide individualized treatment strategies.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"469-478"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of tumor microenvironment in pancreatic cancer on the loss of β-cell mass: implications for type 3c diabetes.","authors":"Ke Hu, Xuelian Zhao, Na Zhang, Jing Ma, Ruonan Zhang, Zhiqiang Lu, Wenchuan Wu, Yuan Ji, Xiaomu Li","doi":"10.1007/s00535-024-02204-w","DOIUrl":"10.1007/s00535-024-02204-w","url":null,"abstract":"<p><strong>Background: </strong>To explore the complex interactions between the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and the loss of β-cell mass, further elucidating the mechanisms of type 3c diabetes mellitus (T3cDM) onset.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was employed to analyze the PDAC TME, identifying cell interactions and gene expression changes of endocrine cells. Pathological changes and paraneoplastic islets were assessed in the proximal paratumor (PP) and distal paratumor (DP). Fractional β-cell area and islet density were compared among normal pancreas from donors and paraneoplastic tissues from non-diabetes mellitus (NDM) and T3cDM patients. TUNEL staining, RT-qPCR and CCK8 assay were applied to demonstrate the β-cell apoptosis.</p><p><strong>Results: </strong>Tumor cells, immune cells and fibroblasts could interact with endocrine cells, and apoptotic pathways were activated in endocrine cells of the PP. The PDAC TME was characterized by marked inflammation, sever fibrosis and atrophy. The islets in the PP had lower fractional β-cell area (0.68 ± 0.65% vs. 0.86 ± 1.02%, P = 0.037) and islet density (0.54 ± 0.42 counts/mm² vs. 0.83 ± 0.90 counts/mm², P = 0.001) compared to those in the DP. The PDAC TME in T3cDM exerted a more significant impact on the paraneoplastic islets compared to NDM. Moreover, β-cell apoptosis was markedly increased in the PP compared to the DP in PDAC patients without diabetes, particularly in smaller islets. Apoptosis-related genes were highly expressed in INS-1E cells exposed to PANC-1 medium.</p><p><strong>Conclusion: </strong>Our research revealed that the PDAC TME is usually accompanied by some pathological changes, including inflammation, fibrosis, and atrophy. These pathological changes are related to a reduction in β-cell mass and trigger the development of T3cDM.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"512-525"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multistage deep learning for classification of Helicobacter pylori infection status using endoscopic images.","authors":"Guang Li, Ren Togo, Katsuhiro Mabe, Shunpei Nishida, Yoshihiro Tomoda, Fumiyuki Shiratani, Masashi Hirota, Takahiro Ogawa, Miki Haseyama","doi":"10.1007/s00535-024-02209-5","DOIUrl":"10.1007/s00535-024-02209-5","url":null,"abstract":"<p><strong>Background: </strong>The automated classification of Helicobacter pylori infection status is gaining attention, distinguishing among uninfected (no history of H. pylori infection), current infection, and post-eradication. However, this classification has relatively low performance, primarily due to the intricate nature of the task. This study aims to develop a new multistage deep learning method for automatically classifying H. pylori infection status.</p><p><strong>Methods: </strong>The proposed multistage deep learning method was developed using a training set of 538 subjects, then tested on a validation set of 146 subjects. The classification performance of this new method was compared with the findings of four physicians.</p><p><strong>Results: </strong>The accuracy of our method was 87.7%, 83.6%, and 95.9% for uninfected, post-eradication, and currently infected cases, respectively, whereas that of the physicians was 81.7%, 76.5%, and 90.3%, respectively. When including the patient's H. pylori eradication history information, the classification accuracy of the method was 92.5%, 91.1%, and 98.6% for uninfected, post-eradication, and currently infected cases, respectively, whereas that of the physicians was 85.6%, 85.1%, and 97.4%, respectively.</p><p><strong>Conclusion: </strong>The new multistage deep learning method shows potential for an innovative approach to gastric cancer screening. It can evaluate individual subjects' cancer risk based on endoscopic images and reduce the burden of physicians.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"408-415"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of preceding treatment for head and neck squamous cell carcinoma on synchronous superficial esophageal squamous cell carcinoma.","authors":"Tomoya Ueda, Ryu Ishihara, Yasuhiro Tani, Yoshiaki Ando, Gentaro Tanabe, Yuta Fujimoto, Noriaki Ito, Nobutoshi Tsukuda, Kazuki Matsuyama, Muneshin Morita, Minoru Kato, Shunsuke Yoshii, Satoki Shichijo, Takashi Kanesaka, Sachiko Yamamoto, Koji Higashino, Noriya Uedo, Tomoki Michida, Takashi Fujii","doi":"10.1007/s00535-024-02201-z","DOIUrl":"10.1007/s00535-024-02201-z","url":null,"abstract":"<p><strong>Background: </strong>Patients with esophageal squamous cell carcinoma (ESCC) frequently develop synchronous head and neck squamous cell carcinoma (HNSCC). With advances in endoscopic technology and widespread screening of synchronous cancers, the detection of synchronous HNSCC and superficial ESCC (SESCC) is increasing. We aimed to evaluate the impact of preceding HNSCC treatment on synchronous SESCC.</p><p><strong>Methods: </strong>This single-center retrospective study enrolled patients with synchronous HNSCC and SESCC who were treated between January 2010 and December 2023. Tumor size and depth of SESCC before and after HNSCC treatment were evaluated. The factors associated with SESCC progression were investigated.</p><p><strong>Results: </strong>Of the 299 patients with synchronous HNSCC and SESCC, 134 who underwent preceding HNSCC treatment with follow-up esophagogastroduodenoscopy (EGD) for SESCC were evaluated. Chemoradiotherapy was the most common treatment for HNSCC (56.0%), followed by surgery (17.2%), radiotherapy (14.9%), local resection (7.5%), and chemotherapy (4.5%). The tumor size of SESCC increased after HNSCC treatment in 18 patients (13.4%). Multivariate analysis revealed that an EGD interval of ≥ 120 days was significantly associated with increased tumor size in SESCC (odds ratio, 6.64; 95% confidence interval, 1.91-23.1). Tumor regrowth was observed in 70.6% of SESCCs that shrank with HNSCC treatment, mostly within six months. Tumor depth aggravation was rare (2.2%), but progression to advanced ESCC was observed in two patients.</p><p><strong>Conclusions: </strong>Timely endoscopic follow-up, preferably within 120 days, is crucial for managing synchronous SESCC after HNSCC treatment to prevent tumor progression. Tumor regrowth should be monitored when SESCC shrinks with HNSCC treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"397-407"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study.","authors":"Makoto Naganuma, Hisashi Shiga, Masayuki Shimoda, Minoru Matsuura, Kento Takenaka, Toshimitsu Fujii, Shojiro Yamamoto, Mao Matsubayashi, Taku Kobayashi, Nobuo Aoyama, Daisuke Saito, Kaoru Yokoyama, Kei Moriya, Kiichiro Tsuchiya, Shunsuke Shibui, Ami Kawamoto, Hiromichi Shimizu, Ryuichi Okamoto, Kazuki Sakamoto, Katsuki Yaguchi, Reiko Kunisaki, Shintaro Akiyama, Ryohei Hayashi, Keisuke Hasui, Shuji Kanmura, Shigeki Bamba, Yoshiyuki Mishima, Kazuki Kakimoto, Shinya Sugimoto, Atsushi Nakazawa, Takayuki Abe, Haruhiko Ogata, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02216-0","DOIUrl":"10.1007/s00535-025-02216-0","url":null,"abstract":"<p><strong>Background: </strong>Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC.</p><p><strong>Methods: </strong>This multicenter, randomized control trial was conducted across 20 Japanese medical institutions. An independent center randomly allocated patients with UC (Mayo score ≥ 6) who had not previously used biologics to three treatment groups (IFX, VED, UST). The primary endpoint was the clinical remission (CR) rate at week 12, with other endpoints including the treatment continuation rate at week 26 and adverse events (AEs).</p><p><strong>Results: </strong>From May 2021 to June 2023, 107 cases were registered, including 104 for safety and 97 for efficacy evaluation. CR rate at week 12 was 36.4% (95%CI:20.4-54.9), 32.4% (95%CI:17.4-50.5) and 43.3% (95%CI:25.5-62.6) in IFX, VED, and UST group, respectively. Continuation rates at week 26 were 50.0%(IFX), 58.3% (VED), and 82.4% (UST). AEs related to study medication were 14.7% (IFX), 16.7% (VED), and 5.9% (UST). Predictors for CR at week 12 were thiopurine use in IFX (p = 0.04), lower baseline Mayo score (p = 0.007), and lower Patient report outcome 2 (p = 0.003) at week 2 in VED.</p><p><strong>Conclusion: </strong>Due to small sample size, it is challenging to make conclusions for main endpoints from this study while our study suggested that use of thiopurines in IFX group and lower activity at enrollment in VED group may enhance treatment efficacy. (jRCT1031200329; available at https://jrct.niph.go.jp/ ).</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"430-441"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Fungal mycobiome dysbiosis in choledocholithiasis concurrent with cholangitis.","authors":"Zhiyuan Hao, Yiting Lu, Yarong Hao, Yuanyuan Luo, Kaiming Wu, Changpeng Zhu, Peimei Shi, Feng Zhu, Yong Lin, Xin Zeng","doi":"10.1007/s00535-025-02217-z","DOIUrl":"10.1007/s00535-025-02217-z","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"528-534"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-fetoprotein combined with initial tumor shape irregularity in predicting the survival of patients with advanced hepatocellular carcinoma treated with immune-checkpoint inhibitors: a retrospective multi-center cohort study.","authors":"Feng Zhang, Yong-Shuai Wang, Shao-Peng Li, Bin Zhao, Nan Huang, Rui-Peng Song, Fan-Zheng Meng, Zhi-Wen Feng, Shen-Yu Zhang, Hua-Chuan Song, Xiao-Peng Chen, Lian-Xin Liu, Ji-Zhou Wang","doi":"10.1007/s00535-024-02202-y","DOIUrl":"10.1007/s00535-024-02202-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are playing a significant role in the treatment of hepatocellular carcinoma (HCC). This study aims to explore the prognostic value of alpha-fetoprotein (AFP) and initial tumor shape irregularity in patients treated with ICIs.</p><p><strong>Methods: </strong>In this retrospective, multi-center study, 296 HCC patients were randomly divided into the training set and the validation set in a 3:2 ratio. The training set was used to evaluate prognostic factors and to develop an easily applicable ATSI (AFP and Tumor Shape Irregularity) score, which was verified in the validation set.</p><p><strong>Results: </strong>The ATSI score was developed from two independent prognostic risk factors: baseline AFP ≥ 400 ng/ml (HR 1.73, 95% CI 1.01-2.96, P = 0.046) and initial tumor shape irregularity (HR 1.94, 95% CI 1.03-3.65, P = 0.041). The median overall survival (OS) was not reached (95% CI 28.20-NA) in patients who met no criteria (0 points), 25.8 months (95% CI 14.17-NA) in patients who met one criterion (1 point), and 17.03 months (95% CI 11.73-23.83) in patients who met two criteria (2 points) (P = 0.001). The median progression-free survival (PFS) was 10.83 months (95% CI 9.27-14.33) for 0 points, 8.03 months (95% CI 6.77-10.57) for 1 point, and 5.03 months (95% CI 3.83-9.67) for 2 points (P < 0.001). The validation set effectively verified these results (median OS, 37.43/24.27/14.03 months for 0/1/2 points, P = 0.028; median PFS, 13.93/8.30/4.90 months for 0/1/2 points, P < 0.001).</p><p><strong>Conclusions: </strong>The ATSI score can effectively predict prognosis in HCC patients receiving ICIs.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"442-455"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated A2F bisect N-glycans of serum IgA reflect progression of liver fibrosis in patients with MASLD.","authors":"Hisatoshi Hanamatsu, Goki Suda, Masatsugu Ohara, Koji Ogawa, Nobuharu Tamaki, Hayato Hikita, Hiroaki Haga, Shinya Maekawa, Masaya Sugiyama, Tatsuhiko Kakisaka, Masato Nakai, Takuya Sho, Nobuaki Miura, Masayuki Kurosaki, Yasuhiro Asahina, Akinobu Taketomi, Yoshiyuki Ueno, Tetsuo Takehara, Takashi Nishikaze, Jun-Ichi Furukawa, Naoya Sakamoto","doi":"10.1007/s00535-024-02206-8","DOIUrl":"10.1007/s00535-024-02206-8","url":null,"abstract":"<p><strong>Background: </strong>Advanced liver fibrosis in cases of metabolic dysfunction-associated steatotic liver disease (MASLD) leads to cirrhosis and hepatocellular carcinoma. The current gold standard for liver fibrosis is invasive liver biopsy. Therefore, a less invasive biomarker that accurately reflects the stage of liver fibrosis is highly desirable.</p><p><strong>Methods: </strong>This study enrolled 269 patients with liver biopsy-proven MASLD. Patients were divided into three groups (F0/1 (n = 41/85), F2 (n = 47), and F3/4 (n = 72/24)) according to fibrosis stage. We performed serum N-glycomics and identified glycan biomarker for fibrosis stage. Moreover, we explored the carrier proteins and developed a sandwich ELISA to measure N-glycosylation changes of carrier protein.</p><p><strong>Results: </strong>Comprehensive N-glycomic analysis revealed significant changes in the expression of A2F bisect and its precursors as fibrosis progressed. The sum of neutral N-glycans carrying bisecting GlcNAc and core Fuc (neutral sum) had a better diagnostic performance to evaluate advanced liver fibrosis (AUC = 0.804) than conventional parameters (FIB4 index, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), and serum level of Mac-2-binding protein glycol isomer (M2BPGi). The combination of the neutral sum and FIB4 index enhanced diagnostic performance (AUC = 0.840). IgM, IgA, and complement C3 were identified as carrier proteins with A2F bisect N-glycan. A sandwich ELISA based on N-glycans carrying bisecting GlcNAc and IgA showed similar diagnostic performance than the neutral sum.</p><p><strong>Conclusions: </strong>A2F bisect N-glycan and its precursors are promising candidate biomarkers for advanced fibrosis in MASLD patients. Analysis of these glycan alterations on IgA may have the potential to serve as a novel ELISA diagnostic tool for MASLD in routine clinical practice.</p><p><strong>Clinical trial number: </strong>UMIN000030720.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"456-468"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative multi-omics analysis reveals a multi-analyte signature of pancreatic ductal adenocarcinoma in serum.","authors":"Rex Devasahayam Arokia Balaya, Partho Sen, Caroline W Grant, Roman Zenka, Marimuthu Sappani, Jeyaseelan Lakshmanan, Arjun P Athreya, Richard K Kandasamy, Akhilesh Pandey, Seul Kee Byeon","doi":"10.1007/s00535-024-02197-6","DOIUrl":"10.1007/s00535-024-02197-6","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC.</p><p><strong>Methods: </strong>We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC.</p><p><strong>Results: </strong>We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites.</p><p><strong>Conclusions: </strong>Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"496-511"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver fibrotic burden across the spectrum of hypothyroidism.","authors":"Tingting Du, Yuchai Huang, Yongman Lv, Gang Yuan","doi":"10.1007/s00535-024-02184-x","DOIUrl":"10.1007/s00535-024-02184-x","url":null,"abstract":"<p><strong>Background: </strong>Data regarding the prevalence of hepatic fibrotic burden across the spectrum of hypothyroidism are scarce. Hence, we aimed to evaluate the prevalence of liver fibrotic burden across the spectrum of hypothyroidism.</p><p><strong>Methods: </strong>30,091 individuals who attended a Health Management Centre between 2019 and 2021 were cross-sectionally analyzed. Participants were categorized as having strict-normal thyroid function, low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism. Hepatic fibrosis was assessed by vibration-controlled transient elastography (VCTE). Significant and advanced fibrosis were defined as liver stiffness measurement in VCTE of 8.1-9.6 and 9.7-13.5 kPa, respectively.</p><p><strong>Results: </strong>Among both men and women, low-normal thyroid function group, subclinical hypothyroidism group, and overt hypothyroidism group all have more liver fibrosis present, including mild fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, than the strict-normal thyroid function group. The low-normal thyroid function group have the similar liver fibrotic burden to the subclinical hypothyroidism group. The highest liver fibrotic burden was noted in the overt hypothyroidism group. Both significant and advanced liver fibrosis were significantly associated with low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism in both men and women.</p><p><strong>Conclusions: </strong>Liver fibrotic burden are highly prevalent in subjects with overt hypothyroidism. Moreover, fibrotic burden increased across the spectrum of hypothyroidism even within the low normal thyroid function. These results suggested that screening for liver fibrosis in patients with hypothyroidism is necessary.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"315-327"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}