Ming Chen , Yuan Yang , Guangsheng Hu , Zhong Peng , Wu Wen
{"title":"The promoting effect of the POU3F2/METTL16/PFKM cascade on glycolysis and tumorigenesis of hepatocellular carcinoma","authors":"Ming Chen , Yuan Yang , Guangsheng Hu , Zhong Peng , Wu Wen","doi":"10.1016/j.aohep.2025.101776","DOIUrl":"10.1016/j.aohep.2025.101776","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Deregulation of m<sup>6</sup>A methylation, the most prevailing RNA modification, participates in cancer pathogenesis. METTL16, an atypical methyltransferase, functions as a pro-tumorigenic factor in hepatocellular carcinoma (HCC). Here, we explored the action of METTL16 on HCC glycolysis and the associated mechanism.</div></div><div><h3>Materials and Methods</h3><div>Expression analysis was done by quantitative PCR, immunoblotting, or immunohistochemistry. Cell sphere formation, invasiveness, apoptosis, proliferation and viability were detected by sphere formation, transwell, flow cytometry, EdU and CCK-8 assays, respectively. Xenograft studies were performed to analyze the role <em>in vivo</em>. Methylated RNA immunoprecipitation (MeRIP) and RIP assays were used to verify the METTL16/PFKM relationship. <em>PFKM</em> mRNA stability was tested by actinomycin D treatment. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to analyze the POU3F2/<em>METTL16</em> relationship.</div></div><div><h3>Results</h3><div>In HCC, METTL16 expression was elevated, and increased levels of <em>METTL16</em> transcript predicted poor HCC prognosis. METTL16 deficiency resulted in suppressed HCC cell growth, invasiveness and sphere formation. Moreover, METTL16 depletion diminished HCC cell glycolysis. Mechanistically, PFKM expression was positively associated with METTL16 expression. METTL16 mediated m6A methylation to stabilize <em>PFKM</em> mRNA via an IGF2BP3-dependent manner. Restored PFKM expression exerted a counteracting effect on METTL16 deficiency-mediated <em>in vitro</em> cell phenotype alterations and <em>in vivo</em> xenograft growth suppression. Furthermore, POU3F2 promoted the transcription of <em>METTL16</em> in HCC cells.</div></div><div><h3>Conclusions</h3><div>Our findings define the crucial role of the POU3F2/METTL16/PFKM axis in HCC pathogenesis, offering the potential opportunity to combat HCC.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 2","pages":"Article 101776"},"PeriodicalIF":3.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930345","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 letter to the editor by Rodriguez S et al.","authors":"Carlos Moctezuma-Velazquez","doi":"10.1016/j.aohep.2024.101770","DOIUrl":"10.1016/j.aohep.2024.101770","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101770"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794325","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":"The dual role of HCV protein expression in communication between host cells presents potential applications in the treatment of liver fibrosis","authors":"Junxi Liu, Boda Zhou","doi":"10.1016/j.aohep.2024.101747","DOIUrl":"10.1016/j.aohep.2024.101747","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101747"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765632","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}
Yiyuan Xiao , Sihua Xu , Wenyan Hu , Jiapeng Huang , Deke Jiang , Rong Na , Zhaoqing Yin , Jingjing Zhang , Haitao Chen
{"title":"Metabolic dysfunction-associated steatotic liver disease and risk of four intrahepatic and extrahepatic diseases","authors":"Yiyuan Xiao , Sihua Xu , Wenyan Hu , Jiapeng Huang , Deke Jiang , Rong Na , Zhaoqing Yin , Jingjing Zhang , Haitao Chen","doi":"10.1016/j.aohep.2024.101750","DOIUrl":"10.1016/j.aohep.2024.101750","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Recently, Delphi consensus proposed an overarching term steatotic liver disease (SLD), with various subcategories such as MASLD, MetALD and ALD. Our aim was to investigate the association between MASLD/MetALD/ALD and four intrahepatic and extrahepatic diseases (liver diseases, renal diseases, cardiovascular diseases, and cancers) in the UK Biobank cohort.</div></div><div><h3>Patients and Methods</h3><div>By defining hepatic steatosis as image-derived phenotype (IDP)-PDFF >5.21%, we used data from the UK Biobank to diagnose MASLD/ MetALD/ALD. The odd ratio (OR) and the hazard ratio (HR) were calculated using the logistic regression modals and Cox regression models, respectively.</div></div><div><h3>Results</h3><div>Among 39,230 eligible individuals, 6,865 MASLD subjects, 2,379 MetALD subjects and 884 ALD subjects were diagnosed. The last follow-up time was October 13, 2023. Consistent with the logistic analyses, MASLD/MetALD/ALD were significantly associated with a higher risk of liver diseases (HR=3.04 [95%CI:2.60-3.56], HR = 2.69 [95% CI: 2.12-3.42] and HR =3.99 [95%CI:2.92-5.45], respectively). Subjects with MASLD also had an increased higher risk of renal diseases (HR = 1.40 [95%CI:1.20-1.64]) and subjects with ALD had an increased higher risk of cancers (HR = 1.36 [95%CI:1.15-1.60]).</div></div><div><h3>Conclusion</h3><div>It is the first study to report the association between MASLD, MetALD, ALD and common intrahepatic and extrahepatic diseases based on magnetic resonance imaging data—PDFF. We found that MASLD, MetALD and ALD were risk factors for liver diseases. Meanwhile, MASLD was also a risk factor for renal diseases and ALD was a risk factor for cancers.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101750"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783883","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}
Santiago Rodríguez Villafuerte , Giacomo Balbinotto Netto , Ajacio Brandão
{"title":"Letter to the editor—Opinion on article by Rodriguez-Alvarez F et al.","authors":"Santiago Rodríguez Villafuerte , Giacomo Balbinotto Netto , Ajacio Brandão","doi":"10.1016/j.aohep.2024.101771","DOIUrl":"10.1016/j.aohep.2024.101771","url":null,"abstract":"","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101771"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798669","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}
Chia-Wen Lu , Tzu-Jung Chou , Tsan-Yu Wu , Yi-Hsuan Lee , Hung-Jen Yang , Kuo-Chin Huang
{"title":"PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population","authors":"Chia-Wen Lu , Tzu-Jung Chou , Tsan-Yu Wu , Yi-Hsuan Lee , Hung-Jen Yang , Kuo-Chin Huang","doi":"10.1016/j.aohep.2024.101761","DOIUrl":"10.1016/j.aohep.2024.101761","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Lean adults with nonalcoholic fatty liver disease (NAFLD) have a higher risk of metabolic syndrome than lean controls. The study aimed to investigate the clinical and genetic features of lean NAFLD which remain unclear in Asian populations.</div></div><div><h3>Materials and Methods</h3><div>This was a genetic cohort study conducted in the HAVO Health Exam Clinic in 2020–2021 in Taiwan. Adults with a body mass index less than 24 kg/m<sup>2</sup> were enrolled. Fatty liver was defined by ultrasonography. The candidate gene approach was based on the library of the NHGRI-EBI website. After removing duplication and nonsignificant variants, rs738409 in the PNPLA3 gene and rs3761472 in the SAMM50 gene were chosen. Multiple logistic regression models and receiver operating characteristic (ROC) curves were used.</div></div><div><h3>Results</h3><div>A total of 1652 lean controls and 602 lean NAFLD patients were enrolled. The average age was 43.8 ± 11.5 years. Lean NAFLD subjects were older and had a higher percentage of metabolic syndrome (case vs. control: 10.5 % vs. 1.5 %). The GG genotypes of PNPLA3 rs12483959 (OR: 3.06; 95% CI: 2.15–4.37) and SAMM50 rs3761472 (OR: 2.90; 95% CI: 2.04–4.14) had a higher risk of fatty liver after adjusting for BMI and metabolic syndrome. The areas under the ROC curve for PNPLA3 rs738409 and SAMM50 rs3761472 in the detection of lean NAFLD were 0.859 (95%CI: 0.841, 0.877) and 0.860 (95%CI: 0.843, 0.877), respectively.</div></div><div><h3>Conclusions</h3><div>PNPLA3 rs738409 and SAMM50 rs3761472 gene polymorphisms are associated with a higher risk of fatty liver in lean individuals independent of BMI and metabolic syndrome in Asian populations.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101761"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783885","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}
Hao Jiang , Hongsheng Yu , Can Hu , Yinan Huang , Bilan Yang , Xiaoli Xi , Yiming Lei , Bin Wu , Yidong Yang
{"title":"Liver stiffness measurement trajectory analysis for prognosis in patients with chronic hepatitis B and compensated advanced chronic liver disease","authors":"Hao Jiang , Hongsheng Yu , Can Hu , Yinan Huang , Bilan Yang , Xiaoli Xi , Yiming Lei , Bin Wu , Yidong Yang","doi":"10.1016/j.aohep.2025.101788","DOIUrl":"10.1016/j.aohep.2025.101788","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Liver stiffness measurements (LSMs) offer a noninvasive method for monitoring liver disease development. This study evaluated the prognostic value of different LSM trajectories in chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD) patients.</div></div><div><h3>Materials and Methods</h3><div>We retrospectively analyzed 1272 CHB and cACLD patients with at least two LSMs, applied group-based trajectory modeling (GBTM) to identify distinct LSM trajectories, and used a Cox model to analyze their associations with liver-related events (LREs) and mortality risk.</div></div><div><h3>Results</h3><div>Patients were categorized into five groups with distinct LSM trajectories: 67 (8.5 %), 13 (11 %), 36 (23.5 %), 34 (27.6 %) and 23 (25.0 %) developed LREs in Groups 1–5. The low stable trajectory (Group 3), the medium gradual decrease trajectory (Group 4) and high quickly decrease followed by increase trajectory (Group 5) had higher LREs risks than the low gradual decrease trajectory (Group 1) (adjusted HRs 2.26, 2.39, 2.67; 95 % CIs 1.50–3.40, 1.57–3.66, 1.61–4.43, respectively). Similar elevated risks were observed for hepatic decompensation, hepatocellular carcinoma (HCC), liver-related and all-cause mortality, except that there was no significant difference in the risk of HCC between Groups 4 and 1 (aHR 0.66, 0.36–1.23). When comparing Group 1 with the medium quickly decrease trajectory (Group 2), no significant differences were noted in the prognosis (<em>P</em> > 0.05). Notably, age over 40, high LSM, low PLT, and high total bilirubin were linked to high-risk trajectories (Groups 3–5).</div></div><div><h3>Conclusions</h3><div>Monitoring LSM trajectories improves prognostic prediction in CHB and cACLD compared with single measurements and may guide personalized treatment strategies.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101788"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603606","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":"Clinical usefulness of an ultra-high-sensitivity hepatitis B surface antigen assay to determine the cessation of treatment for HBV reactivation","authors":"Takanori Suzuki , Akihiro Tamori , Kentaro Matsuura , Takako Inoue , Shigeru Kusumoto , Shinya Hagiwara , Haruka Sagi , Atsushi Kaneko , Shuko Murakami , Hayato Kawamra , Kei Fujiwara , Katsumi Aoyagi , Masaru Enomoto , Ritsuzo Kozuka , Hiromi Kataoka , Yasuhito Tanaka","doi":"10.1016/j.aohep.2024.101764","DOIUrl":"10.1016/j.aohep.2024.101764","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>We aimed to compare the usefulness of the ultra-high-sensitivity hepatitis B surface antigen (iTACT-HBsAg), high-sensitivity hepatitis B core-related antigen (iTACT-HBcrAg), and anti-HBs assays in determination of cessation of nucleot(s)ide analogue (NA) treatment to prevent against hepatitis B virus (HBV) reactivation.</div></div><div><h3>Patients and Methods</h3><div>Twenty-two patients who developed HBV reactivation under immunosuppressive therapy or chemotherapy and had been administered NA and subsequently discontinued were enrolled. The stored serum samples taken at NA cessation were applied to iTACT-HBsAg (lower limit of detection; 0.0005 IU/mL), iTACT-HBcrAg (lower limit of detection; 2.1 log U/mL), and anti-HBs assays. Detection of serum HBV DNA level ≥1.3 log IU/mL after NA cessation was defined as virological relapse (VR).</div></div><div><h3>Results</h3><div>Two patients were excluded due to re-introduction of NA despite a negligible level of HBV DNA (<1.3 log IU/mL). Of the remaining 20 patients, 11 (55 %) had HBcrAg <2.1 log U/mL at the cessation of NA, and 7 of the 11 patients (64 %) had no VR thereafter. On the other hand, 15 patients (75 %) had HBsAg <0.0005 IU/mL at the cessation of NA, and 13 of the 15 patients (87 %) subsequently lacked VR. Further, 12 patients (60 %) had anti-HBs ≥10 mIU/mL at the cessation of NA, and 10 of the 12 patients (83 %) had no VR thereafter. The iTACT-HBsAg assay had the highest positive predictive value and the best overall diagnostic performance for predicting non-VR after cessation of NA.</div></div><div><h3>Conclusions</h3><div>The iTACT-HBsAg assay was useful to determine the cessation of NA treatment to prevent against HBV reactivation.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101764"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783879","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}
Iván López-Mendez , Juan Luis Romero-Flores , Graciela Castro-Narro , Misael Uribe , Eva Juárez-Hernández
{"title":"Factors associated with obtaining lower IQR-CAP values in the detection of hepatic steatosis by transient elastography","authors":"Iván López-Mendez , Juan Luis Romero-Flores , Graciela Castro-Narro , Misael Uribe , Eva Juárez-Hernández","doi":"10.1016/j.aohep.2024.101762","DOIUrl":"10.1016/j.aohep.2024.101762","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><div>Controlled attenuation parameter (CAP) has been developed as a non-invasive method for detecting liver steatosis. The aim of the study was to determine factors associated with non-obtaining lower IQR-CAP values.</div></div><div><h3>Materials and Methods</h3><div>Retrospective revision of medical records of CAP studies for steatosis screening. Anthropometrical, biochemical, and quality variables were collected. A logistic regression analysis was performed to determine independent associations with non-obtaining IQR-CAP <30, <20, and <10 in all patients and then adjusted for obesity/overweight and severity of steatosis.</div></div><div><h3>Results</h3><div>5061 studies were analyzed. Median IQR-CAP was 26 [IQR 20–33] dB/m. Steatosis prevalence was 39.4 % (<em>n</em> = 1996). In overweight patients, significant alcohol consumption was an independent factor for non-obtaining IQR-CAP <30; meanwhile, in obese patients glucose impairment, AST, skPa>8 and steatosis severity were independent factors for non-obtaining lower IQR-CAP values. According to steatosis severity, the presence of anthropometric characteristics of obesity and significant alcohol consumption were independent factors for non-obtaining lower IQR-CAP values.</div></div><div><h3>Conclusions</h3><div>In steatosis detection by CAP, obesity, significant alcohol consumption, glucose impairments, and minimal liver function test alterations were independent factors associated with non-obtaining lower values of IQR-CAP.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101762"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783882","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}
Jacqueline Cordova-Gallardo , Andres Manuel Vargas-Beltran , Samantha Melanie Armendariz-Pineda , Jesus Ruiz-Manriquez , Javier Ampuero , Aldo Torre
{"title":"Brain reserve in hepatic encephalopathy: Pathways of damage and preventive strategies through lifestyle and therapeutic interventions","authors":"Jacqueline Cordova-Gallardo , Andres Manuel Vargas-Beltran , Samantha Melanie Armendariz-Pineda , Jesus Ruiz-Manriquez , Javier Ampuero , Aldo Torre","doi":"10.1016/j.aohep.2024.101740","DOIUrl":"10.1016/j.aohep.2024.101740","url":null,"abstract":"<div><div>Brain reserve is an important concept to understand the variability of damage associated with brain-related diseases and includes the adaptation of cognitive processes to preserve brain function. A good cognitive reserve might delay the onset of clinical manifestations of neurodegenerative diseases as well as hepatic encephalopathy, improving the quality of life in patients with chronic liver diseases. By stimulating activities and maintaining overall health, individuals may be able to enhance their brain's resilience to age-related changes and pathology. This review aims to collect all the data available on the role of brain reserve in hepatic encephalopathy development, and the potential effect of a good brain reserve in slowing down hepatic encephalopathy progression and frequency.</div></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":"30 1","pages":"Article 101740"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765611","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}