Clinical and Molecular Hepatology最新文献

{"title":"Letter \"Radiogenomics of intrahepatic cholangiocarcinoma predicts immunochemotherapy response and identifies therapeutic target\".","authors":"Yuqian Liu, Ruiyun Guo, Jun Ma","doi":"10.3350/cmh.2025.0377","DOIUrl":"https://doi.org/10.3350/cmh.2025.0377","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HTD1801 Demonstrates Promising Potential for Histologic Improvements in MASH in Both a Preclinical and Phase 2 Study.","authors":"Vincent Wai-Sun Wong, Guy W Neff, Adrian M Di Bisceglie, Ru Bai, Junwei Cheng, Meng Yu, Alexander Liberman, Liping Liu, Nadege Gunn","doi":"10.3350/cmh.2025.0145","DOIUrl":"https://doi.org/10.3350/cmh.2025.0145","url":null,"abstract":"<p><strong>Background & aims: </strong>Berberine ursodeoxycholate (HTD1801) has been shown to significantly reduce liver fat content (LFC) in an 18-week, placebo-controlled Phase 2 study in patients with metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes (T2DM). The purpose of this assessment was to establish proof of concept in liver histologic improvement with HTD1801 treatment based on preclinical and clinical evidence.</p><p><strong>Methods: </strong>The efficacy of HTD1801 was evaluated in a preclinical MASH/dyslipidemia model (golden hamsters fed a high fat diet, eight/group) after six weeks of daily treatment. Additionally, in a secondary analysis of a Phase 2 clinical study, 100 patients with presumed MASH were evaluated by multiple noninvasive markers associated with MASH resolution and/or fibrosis improvement. These include magnetic resonance imaging proton density fat fraction (MRI-PDFF; ≥30% LFC reduction), iron-corrected T1 (≥80 ms reduction), alanine aminotransferase (≥17 U/L reduction), weight loss (≥5% reduction), Fibrosis-4 index (shift to <1.3), and MASH Resolution Index (achieving ≥‑0.67).</p><p><strong>Results: </strong>Preclinical findings in the MASH/dyslipidemia hamster model showed that HTD1801 significantly improved histologic fibrosis and the Nonalcoholic Fatty Liver Disease Activity Score to such a degree that improvements approximated the appearance of the normal controls. In the clinical study, 52% of HTD1801-treated patients achieved MRI response criteria compared to 24% of placebo (p<0.05). Dose-dependent improvements were observed across biomarkers, with more HTD1801-treated patients achieving response criteria associated with improvements in the histologic features of MASH.</p><p><strong>Conclusions: </strong>These findings suggest that HTD1801 has strong potential to produce histological improvements in patients with MASH.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease.","authors":"Eiji Kakazu, Masaaki Mino, Tatsuya Kanto","doi":"10.3350/cmh.2025.0048","DOIUrl":"https://doi.org/10.3350/cmh.2025.0048","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and its relatively advanced form, metabolic dysfunction-associated steatohepatitis (MASH), are becoming increasingly prevalent worldwide, making their prevention and management an urgent global health priority. Central to their development are key metabolic defects, including abnormal concentrations of monosaccharides, fatty acids, and amino acids, but the complex relationships between these substances within the hepatic microenvironment remain only partially understood. Dysregulated glucose metabolism and selective insulin resistance (IR) promote hepatic gluconeogenesis, glycolysis, and de novo lipogenesis (DNL); and excessive concentrations of free fatty acids from the diet and adipose tissue drive steatosis. Emerging evidence also implies that amino acid metabolism affects mitochondrial function and redox balance. Dysfunctional mitochondrial oxidative phosphorylation and the associated increase in reactive oxygen species production further exacerbate the cellular stress, inflammation, and fibrosis. However, compared with monosaccharide and fatty acid metabolism, the role of amino acid metabolism in MASLD/MASH remains less well understood. A better understanding of the role of such metabolic dysfunction in liver pathobiology should aid the identification of more useful biomarkers and precision therapies for MASLD/MASH.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Link Between Tumor Cell Metabolism and Patient Prognosis: Editorial on \"Molecular Classification of Hepatocellular Carcinoma based on Zoned Metabolic Feature and Oncogenic Signaling Pathway\".","authors":"Eun Ji Jang, Pil Soo Sung","doi":"10.3350/cmh.2025.0395","DOIUrl":"https://doi.org/10.3350/cmh.2025.0395","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to authors' reply: \"Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis\".","authors":"Mathias Jachs, Mattias Mandorfer","doi":"10.3350/cmh.2025.0391","DOIUrl":"https://doi.org/10.3350/cmh.2025.0391","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence to Editorial on \"Switching to Besifovir in Patients with Chronic Hepatitis B Receiving Tenofovir Disoproxil Fumarate: A Randomized Trial\".","authors":"Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang","doi":"10.3350/cmh.2025.0379","DOIUrl":"https://doi.org/10.3350/cmh.2025.0379","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Disparities in Alcohol-Associated Liver Disease and Subtype Differences in Alcohol-attributable Cancers in the United States.","authors":"Pojsakorn Danpanichkul, Yanfang Pang, Tanuj Mahendru, Primrose Tothanarungroj, Luis Antonio Díaz, Juan Pablo Arab, Pimtawan Jatupornpakdee, Mark D Muthiah, Kwanjit Duangsonk, Won-Mook Choi, Daniel Q Huang, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul, Amit G Singal, Ju Dong Yang","doi":"10.3350/cmh.2025.0169","DOIUrl":"https://doi.org/10.3350/cmh.2025.0169","url":null,"abstract":"<p><strong>Background & aims: </strong>Harmful alcohol use is a substantial contributor to liver diseases, liver cancer, and extrahepatic neoplasms. Patterns of alcohol consumption have shifted over recent decades. This study evaluates trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers in the United States (US) from 2000 to 2021.</p><p><strong>Methods: </strong>Using the methodological framework of the Global Burden of Disease Study 2021, we analyzed trends in incidence, prevalence, and mortality from ALD and alcohol-attributable cancers in the US.</p><p><strong>Results: </strong>In 2021, there were 28,340 new cases of ALD, 227,730 prevalent cases, and 21,860 deaths attributed to ALD in the USA. From 2000 to 2021, ALD incidence, prevalence, and mortality increased by 43%, 36%, and 79%, respectively. The age-standardized incidence and death rate of ALD rose disproportionately among females compared to males. For alcohol-attributable cancers, primary liver cancer, colorectal cancer, and esophageal cancer accounted for the largest share of deaths in 2021. Age-standardized death rates increased significantly for primary liver cancer (Annual Percent Change [APC]: 2.21%, 95% CI: 1.70 to 2.73% and other pharyngeal cancer (APC: 1.35%, 95% CI: 1.08 to 1.62%).</p><p><strong>Conclusion: </strong>The burden of ALD is substantial and continues to rise in the USA, with a particularly notable increase among females. Mortality from alcohol-attributable cancers is also increasing, mainly driven by primary liver cancer and pharyngeal cancer. However, system-wise, gastrointestinal cancer had the highest death attributable to alcohol. These findings highlight the urgent need for public health strategies to tackle ALD, primary liver cancer, and alcohol-attributable extrahepatic malignancies.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on \"GDH1-dependent α-ketoglutarate promotes HBV transcription by modulating histone methylations on the cccDNA minichromosome\".","authors":"Mehrangiz Dezhbord, Kyun-Hwan Kim","doi":"10.3350/cmh.2025.0366","DOIUrl":"https://doi.org/10.3350/cmh.2025.0366","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation.","authors":"Tiantian Wang, Dean Rao, Chenan Fu, Zhoubin Sun, Yiming Luo, Junli Lu, Jie Jin, Han Li, Feimu Fan, Huifang Liang, Wenjie Huang, Limin Xia","doi":"10.3350/cmh.2024.1163","DOIUrl":"https://doi.org/10.3350/cmh.2024.1163","url":null,"abstract":"<p><strong>Background/aims: </strong>Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and abnormal MET expression plays a crucial role in its progression. However, the specific pathogenic mechanisms of MET in HCC have yet to be fully elucidated. This study aimed to uncover the oncogenic mechanisms of MET in HCC and explore potential therapeutic implications.</p><p><strong>Methods: </strong>Transcriptomic data from the HTVi MET/β-catenin HCC model and GSEA results from TCGA LIHC cohorts were analyzed to identify key genes in HCC development. In vitro assays and in vivo models were used to investigate the role of TRIB3 in HCC progression. Immunofluorescence (IF), Co-IP, qRT-PCR, and WB revealed target genes regulated by TRIB3. An AAV8-shTRIB3 construct was developed and we assessed its therapeutic potential.</p><p><strong>Results: </strong>MET promoted HCC development both in vitro and in vivo by upregulating the oncogenic protein TRIB3. Mechanistically, MET transcriptionally activated TRIB3 via the ERK/SP1 axis. TRIB3 then recruited the E3 ubiquitin ligase COP1, which facilitated the ubiquitination and degradation of the tumor suppressor transcription factor FOXO1. TRIB3-mediated FOXO1 ubiquitination up regulated the expression of MET, CTNNB1 and TWIST1. In clinical HCC samples, TRIB3 expression was correlated with MET and FOXO1 levels. Liver-specific knockdown of TRIB3 by AAV8-shTRIB3 significantly inhibited MET-driven HCC development.</p><p><strong>Conclusions: </strong>Our results revealed that TRIB3 and COP1 act as key mediators in MET-driven HCC progression. Targeting the MET-TRIB3-FOXO1 regulatory axis may offer a promising therapeutic strategy to counteract oncogenic signaling and impede HCC advancement.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Health in Antiviral Era of Chronic Hepatitis B.","authors":"Shang-Chin Huang, Jia-Horng Kao","doi":"10.3350/cmh.2025.0369","DOIUrl":"https://doi.org/10.3350/cmh.2025.0369","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}