Liver cancer international最新文献

{"title":"Preascitic Sodium Retention in Cirrhosis: A Role for Disregulated Proteolysis by Proprotein Convertases?","authors":"Giovanni Sansoè,&nbsp;Manuela Aragno,&nbsp;Florence Wong","doi":"10.1002/lci2.70020","DOIUrl":"https://doi.org/10.1002/lci2.70020","url":null,"abstract":"<p>Loss of effective arterial blood volume, secondary hyperaldosteronism, adrenergic activation and nonosmotic hypersecretion of vasopressin induce sodium and water retention in cirrhotic patients with ascites. The mechanisms of sodium retention that precede ascites formation remain elusive. In patients who are at the preascites stage of cirrhosis, no sign of reduced effective volaemia is found; nonetheless, tubular sodium retention is already present. Maturation and full functionality of epithelial sodium channels (ENaC) in distal segments of the nephron and, therefore, final control of sodium excretion are dependent on regulated proteolysis by proprotein convertases. Evidence of abnormal or incomplete maturation of ENaCs in preascitic cirrhosis exists, but the complex mechanisms of regulated proteolysis leading to ENaC maturation through sequential action of serine endopeptidases (i.e., furin, site-1 protease, prostasin, plasmin) have never been studied in liver cirrhosis. Also, the mechanisms of cirrhosis-associated immune dysfunction, which are characterised by systemic sterile inflammation and release of proinflammatory cytokines that profoundly influence renal function, remain largely unknown. Release of proinflammatory cytokines and functions of respective receptors are controlled through regulated proteolysis by cell membrane metallopeptidases (mainly ADAM-10 and -17). Once again, little is known in preascitic cirrhosis about potential disregulated proteolysis of proinflammatory cytokines that may trigger systemic inflammation and renal dysfunction. We advance a new hypothesis that (a) may link proprotein convertases to disregulated proteolysis of tubular sodium channels, renin-angiotensin system receptors and inflammatory mediators, and that (b) may shed light on the mechanisms of sodium retention before any systemic neurohormonal activation in liver cirrhosis.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Type Deconvolution Reveals Dynamic Changes in MASLD","authors":"Jeff J. H. Kim,&nbsp;Yang Dai","doi":"10.1002/lci2.70012","DOIUrl":"https://doi.org/10.1002/lci2.70012","url":null,"abstract":"<p>Metabolic-associated steatotic liver disease (MASLD) is among the most prevalent liver disorders worldwide, with many patients progressing to metabolic-associated steatohepatitis (MASH) characterised by fibrosis and inflammation. The current lack of effective treatments for MASH highlights the urgent need to deepen our understanding of its underlying mechanisms. Examining cellular dynamics—specifically, changes in cell type proportions across disease stages—offers a promising avenue for gaining such insights. However, previous deconvolution analyses have been limited to a few cell types, and a comprehensive analysis encompassing diverse cell populations and their unique subtypes has yet to be conducted. In this study, we employed MuSiC deconvolution to analyse two bulk RNA sequencing datasets spanning the MASLD spectrum across both fibrosis staging and Non-Alcoholic Fatty Liver Disease Activity Score (NAS) staging. Our analysis reveals distinct proportional trends in 10 different cell types, including hepatocytes, cholangiocytes, two subpopulations of hepatic stellate cells, endothelial cells, and immune cells such as kupffer cells, TREM2⁺ macrophages, and plasma B cells. In addition to deconvolution analysis, we integrated cell type proportion data with transcriptomic profiles, significantly enhancing the performance of random forest models in classifying fibrosis stages compared to using transcriptomic data alone. The study's findings highlight critical cellular dynamic changes across MASLD progression, advancing our understanding of the disease mechanisms and potentially informing the development of more effective therapeutic strategies.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Use of Comprehensive Genomic Profiling Tests in Intrahepatic Cholangiocarcinoma: A Single-Center Retrospective Study","authors":"Makiko Urabe,&nbsp;Takuo Yamai,&nbsp;Kenji Ikezawa,&nbsp;Kazuhiro Kozumi,&nbsp;Yugo Kai,&nbsp;Ryoji Takada,&nbsp;Kaori Mukai,&nbsp;Tasuku Nakabori,&nbsp;Hiroshi Wada,&nbsp;Naotoshi Sugimoto,&nbsp;Kazuyoshi Ohkawa","doi":"10.1002/lci2.70017","DOIUrl":"https://doi.org/10.1002/lci2.70017","url":null,"abstract":"<p>The clinical utility of comprehensive genomic profiling (CGP) in intrahepatic cholangiocarcinoma (ICC) remains to be fully elucidated. This study analysed CGP test results and evaluated treatment outcomes with fibroblast growth factor receptor (FGFR) inhibitors in patients with ICC, aiming to assess their efficacy in cases with specific <i>FGFR</i> alterations and to explore how CGP can inform personalised treatment strategies. We retrospectively reviewed clinical data from 52 patients with pathologically confirmed advanced ICC, who successfully underwent the CGP test at a Japanese cancer referral centre between November 2019 and March 2023. The median patient age was 67 years. CGP test identified one patient (1.9%) with a high tumour mutation burden (TMB) and revealed therapeutically relevant oncogenic driver gene alterations in 32.7% of cases. The most frequently detected alterations were <i>FGFR2</i> alterations (15.4%) and isocitrate dehydrogenase 1 mutations (9.6%). Based on CGP results, nine patients—eight with <i>FGFR2</i> fusions or rearrangements and one with high TMB—were eligible for approved targeted therapies. Among these, four patients treated with pemigatinib achieved stable disease, with a median treatment duration of 244 days. Notably, one patient with an <i>FGFR2</i> fusion responded to pemigatinib following futibatinib failure. CGP test, when implemented in a timely manner, can serve as a valuable tool in clinical practice for identifying novel therapeutic options for patients with advanced ICC. Furthermore, sequential therapy with FGFR inhibitors may be an effective strategy for managing patients with <i>FGFR2</i> fusions or rearrangements.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver Disease and Prevalence of Liver Transplantation in Adults With ZZ Alpha-1 Antitrypsin Deficiency—A Meta-Analysis","authors":"Adam M. Syanda,&nbsp;Dimitra Georgantaki,&nbsp;Muhammad Awsaf,&nbsp;Mariam Molokhia,&nbsp;S. Tamir Rashid","doi":"10.1002/lci2.70013","DOIUrl":"https://doi.org/10.1002/lci2.70013","url":null,"abstract":"<p>Alpha-1 antitrypsin deficiency (A1ATD) is an inherited metabolic disorder caused by a mutation (ZZ) in the SERPINA1 gene. Carriers are predisposed to liver and lung pathology. The severity of A1ATD-associated liver disease is highly variable, necessitating further characterisation. This study aims to investigate the risk and extent of liver disease and the prevalence of liver transplantation in ZZ A1ATD patients. Several established databases, including Ovid, EBSCO, PubMed, and Cochrane Library, were searched from inception to May 12, 2024. Data were pooled using a random effects model, and study weight was calculated using the inverse variance method. Crude odds ratios (cOR) were calculated using participants with the MM genotype as the comparator. The study was registered in PROSPERO (CRD42022335666). Of the 4420 studies identified, 45 studies and 8638 A1ATD patients (38.8% female) were included. ZZ A1ATD patients demonstrate an increased risk of liver diseases compared to controls, including steatosis (crude odds ratio (cOR): 1.52 [95% CI: 1.21, 1.91]), fibrosis (cOR: 9.85 [95% CI: 5.70, 17.03]), cirrhosis (cOR: 10.43 [95% CI: 5.51, 19.73]), and liver cancers (cOR: 14.12 [95% CI: 6.50, 30.66]). The prevalence of liver transplantation is considerable, with rates reaching 5% [95% CI: 0.00, 12.34]. Our findings confirm the substantial burden of liver disease in ZZ A1ATD patients, including subclinical manifestations such as steatosis and fibrosis that may remain undetected. Given the lack of approved treatments for A1ATD-associated liver disease, prioritising the development of novel therapies to stop or reverse liver disease is essential.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ECM Biomarkers PRO-C3 and PRO-C6 Reveal the Anti-Fibrotic Effect of the Insulin Sensitizer MSDC-0602 K During EMMINENCE Randomised Clinical Trial","authors":"Alejandro E. Mayorca-Guiliani,&nbsp;Peder Frederiksen,&nbsp;Morten A. Karsdal,&nbsp;Jerry Colca,&nbsp;Diana J. Leeming","doi":"10.1002/lci2.70018","DOIUrl":"https://doi.org/10.1002/lci2.70018","url":null,"abstract":"<p>MSDC-0602 K is a second-generation insulin sensitizer that inhibits the mitochondrial pyruvate carrier without activating the transcription factor PPARγ. The EMMINENCE phase IIb trial evaluated MSDC-0602 K in patients with metabolic dysfunction-associated steatohepatitis (MASH). MSDC-0602 K missed statistical significance on endpoints based on liver histology while producing significant reductions in metabolic biomarkers. Here, we assessed the extracellular matrix-based biomarkers PRO-C3 and PRO-C6, surrogates of collagen type III synthesis and the profibrotic, pro-inflammatory fragment endotrophin. 392 MASH patients were randomised to placebo (PL), 62.5 mg, 125 mg or a 250 mg daily dose of MSDC-0602 K for 12 months. 334 completed the study. The primary efficacy endpoint was defined as an improvement of ≥ 2 points in NAS score, with ≥ 1 decrease in either ballooning or inflammation and no increase in fibrosis stage. Blood samples were collected at baseline, 6 months, and 12 months to assess biochemical markers PRO-C3 and PRO-C6. The 125 mg and 250 mg doses of MSDC-0602 K reduced PRO-C3 at 6 months (<i>p</i> = 0.0103 and <i>p</i> = 0.026 respectively) and 12 months (<i>p</i> = 0.0274 and <i>p</i> = 0.0311) compared to placebo. Furthermore, the 62.5 mg and 250 mg doses reduced PRO-C6 at 12mo (<i>p</i> = 0.0467 and <i>p</i> = 0.0266) compared to placebo. Treated patients who reached the primary endpoint had lower baseline PRO-C3 (<i>p</i> = 0.026), and PRO-C3 levels discriminated between regressing, stable or progressing fibrosis (<i>p</i> = 0.0076). MSDC-0602 K significantly reduced PRO-C3 and PRO-C6, suggesting anti-fibrotic and pro-metabolic effects. Lower baseline fibroblast activity (PRO-C3) at baseline was associated with improvement in fibrosis, while higher baseline PRO-C3 was associated with fibrosis progression. Our findings suggest that MSDC-0602 K has anti-fibrogenesis and pro-metabolic effects not detected by liver histology.</p><p><b>Trial Registration:</b> EMMINENCE clinical trial number (ClinicalTrials.gov NCT02784444)</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Cathepsin B Is a Potential Therapeutic Target in Hepatocellular Carcinoma","authors":"Hester van Mourik,&nbsp;Annemarie Westheim,&nbsp;Carolin Victoria Schneider,&nbsp;Lara Stoffels,&nbsp;Ewa Wieczerzak,&nbsp;Jorn Steeghs,&nbsp;Kai Markus Schneider,&nbsp;Lieve Temmerman,&nbsp;Erik Biessen,&nbsp;Roger Godschalk,&nbsp;Jan Theys,&nbsp;Ronit Shiri-Sverdlov","doi":"10.1002/lci2.70016","DOIUrl":"https://doi.org/10.1002/lci2.70016","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Therapeutic options are limited, and therefore new therapeutic targets are needed. Cathepsins, lysosomal proteases, are implicated in various types of cancer. While intracellular cathepsins have various physiological functions, their extracellular secretion can lead to pathological effects. Cathepsin B (CTSB) stays active at neutral pH and contributes to several liver pathologies, including HCC. However, the mechanisms by which extracellular CTSB contributes to HCC remain unclear. Hence, this study aimed to investigate the role of extracellular CTSB in HCC. Cell and spheroid viability of HepG2 and Huh-7 cells was assessed after treatment with extracellular and intracellular CTSB inhibitors. A chorioallantoic membrane HCC xenograft model was used to study the effect of combined extracellular CTSB inhibitor and chemotherapy treatment on tumour growth, apoptosis, proliferation and angiogenesis. The UK Biobank proteomics data was used to determine the potential role of CTSB in HCC patients. Inhibition of extracellular CTSB significantly decreased the viability of HepG2 and Huh-7 cells in both monolayers and spheroids compared to intracellular CTSB inhibition. The chorioallantoic membrane model demonstrated that extracellular CTSB inhibition decreased the ratio of proliferation-apoptosis and, in the presence of paclitaxel, tumour angiogenesis, which resulted in a smaller tumour mass. Furthermore, compared to healthy controls, HCC patients demonstrated higher plasma levels of CTSB which were associated with a higher mortality risk. In conclusion, targeting extracellular CTSB could be a promising therapeutic strategy for HCC, since it decreases angiogenesis and proliferation, while it increases apoptosis.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytotherapy for Liver Fibrosis: Insights From the Biology of Hepatic Stellate Cells—A Narrative Review","authors":"Sathish Kumar Mungamuri,&nbsp;Nabanita Chatterjee,&nbsp;Dilkash Ara","doi":"10.1002/lci2.70015","DOIUrl":"https://doi.org/10.1002/lci2.70015","url":null,"abstract":"<p>Chronic liver diseases frequently progress to liver fibrosis, characterized by the accumulation of extracellular matrix (ECM) proteins and the formation of fibrous scars. This fibrous tissue disrupts normal liver architecture, impairing its physiological functions. Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure, often necessitating transplantation. Hepatic stellate cells (HSCs) are pivotal in collagen production and play a crucial role in the fibrotic process. Notably, mild to moderate fibrosis can be reversed upon removal of its causative agents, with recovery rates varying based on the cause and severity of fibrosis. Emerging anti-fibrotic therapies focus on inhibiting fibrogenic cell accumulation and preventing ECM deposition. This review highlights herbal extracts with proven effects on HSCs in vivo, showing potential in mitigating liver fibrosis. These extracts inhibit HSC proliferation and ECM release by targeting critical signalling pathways, including TGF-β, NF-κB, MAPK, STAT3 and NRF2. While many of these plants have been validated in pre-clinical studies, further research is needed to identify active compounds and establish clinical efficacy.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Mortality in MASLD: A Matter of Fat. Caution in Interpreting Liver Fat Quantification in Populations With High Fibrosis Variability","authors":"Mohamad Jamalinia,&nbsp;Amedeo Lonardo","doi":"10.1002/lci2.70014","DOIUrl":"https://doi.org/10.1002/lci2.70014","url":null,"abstract":"&lt;p&gt;We read with great interest the recent article by Kim and Vutien, et al., which reports that substantial liver fat, measured via Vibration-controlled Transient Elastography (VCTE), is associated with a reduced risk of decompensation (aHR: 0.54, 95% CI: 0.32–0.90) and mortality (aHR: 0.52, 95% CI: 0.37–0.73) in metabolic dysfunction-associated steatotic liver disease (MASLD) patients [&lt;span&gt;1&lt;/span&gt;]. This study brings valuable insights by examining liver fat's unique prognostic value independent of fibrosis, which has often been overshadowed by an isolated focus on fibrosis. Their findings align with previous meta-analyses showing that lower liver fat content in MASLD individuals with significant/advanced fibrosis is associated with an increased risk of composite adverse outcomes, including decompensation, hepatocellular carcinoma, and death (aHR: 42.2, 95% CI: 7.5–235.5) [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;While commending the authors for this significant contribution, we suggest caution in interpreting steatosis quantification in populations with high variability in fibrosis levels [as indicated by interquartile range (IQR) of 6.4–17.9 (median 10.6 kPa)] in this study [&lt;span&gt;1&lt;/span&gt;]. A large cohort study involving 9.8 million individuals, deemed to be at low risk of advanced fibrosis, illustrated that high Liver fat content, as measured by the surrogate Fatty Liver Index (FLI) was associated with a higher risk of cardiovascular events in MASLD (aHR: 1.39, 95% CI: 1.38–1.40 for FLI ≥ 30 and aHR: 1.52, 95% CI: 1.51–1.54 in FLI ≥ 60) [&lt;span&gt;3&lt;/span&gt;]. Similarly, in a recent meta-analysis of 19 studies involving 147 411 participants, primarily from population-based studies, we found that higher liver fat levels in MASLD were associated with an increased risk of subclinical atherosclerosis (pooled OR: 1.27, 95% CI: 1.13–1.41 for mild steatosis and 1.68, 95% CI: 1.41–2.00 for moderate to severe steatosis) [&lt;span&gt;4&lt;/span&gt;]. However, this association reversed in populations with a high prevalence of significant/advanced fibrosis, in parallel with increasing fibrosis levels [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;This paradox may be explained by the ‘burnout’ NASH phenomenon. As liver disease progresses, alterations in portal circulation—such as reduced blood flow, portosystemic shunting, and loss of sinusoidal fenestrations—diminish hepatocyte interactions with insulin and lipoproteins, leading to decreased hepatic fat accumulation [&lt;span&gt;5&lt;/span&gt;]. Additionally, while low levels of the insulin-sensitising and anti-steatotic adipocytokine adiponectin are linked with hepatic steatosis and inflammation, elevated adiponectin levels in later disease stages may contribute to reduced hepatic fat storage in advanced (burnt-out) MASH with liver dysfunction [&lt;span&gt;6&lt;/span&gt;]. Consequently, individuals with significant/advanced fibrosis may exhibit lower liver fat levels, which could distort associations between steatosis and clinical outcomes, suggesting that fibrosis severity biases ","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol Intake and Cardiometabolic Risk Factors Are Independently Associated With a Higher AST/Platelet Ratio Index in Obese Males","authors":"Hideki Fujii,&nbsp;Yoshihiro Kamada,&nbsp;Yuichiro Suzuki,&nbsp;Koji Sawada,&nbsp;Miwa Tatsuta,&nbsp;Tatsuji Maeshiro,&nbsp;Hiroshi Tobita,&nbsp;Tsubasa Tsutsumi,&nbsp;Takemi Akahane,&nbsp;Chitomi Hasebe,&nbsp;Miwa Kawanaka,&nbsp;Takaomi Kessoku,&nbsp;Yuichiro Eguchi,&nbsp;Hayashi Syokita,&nbsp;Atsushi Nakajima,&nbsp;Tomoari Kamada,&nbsp;Hitoshi Yoshiji,&nbsp;Takumi Kawaguchi,&nbsp;Hiroshi Sakugawa,&nbsp;Asahiro Morishita,&nbsp;Tsutomu Masaki,&nbsp;Takumi Ohmura,&nbsp;Toshio Watanabe,&nbsp;Yoshioki Yoda,&nbsp;Nobuyuki Enomoto,&nbsp;Masafumi Ono,&nbsp;Kanako Fuyama,&nbsp;Kazufumi Okada,&nbsp;Naoki Nishimoto,&nbsp;Yoichi M. Ito,&nbsp;Hirokazu Takahashi,&nbsp;Yoshio Sumida,&nbsp;Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)","doi":"10.1002/lci2.70010","DOIUrl":"https://doi.org/10.1002/lci2.70010","url":null,"abstract":"<p>It remains unclear whether alcohol intake and cardiometabolic factors are simultaneously associated with liver fibrosis progression in Japanese obese patients. This study investigated factors influencing liver fibrosis progression using the Aspartate Aminotransferase/Platelet Ratio Index (APRI), which does not include age. We conducted a cross-sectional study of 26 737 obese (BMI ≥ 25 kg/m²) adults undergoing health checkups. Steatotic liver disease (SLD) was diagnosed via ultrasonography. Clinical characteristics were analysed according to BMI category and APRI to identify risk factors for advanced liver fibrosis (APRI &gt; 1.0). The prevalence of type 2 diabetes, hypertension, and SLD increased with increasing BMI. On multivariable analysis in male, significant risk factors for advanced liver fibrosis included increased BMI (BMI 30–34.9 kg/m²: OR 2.64, 95% CI 1.89–3.69, <i>p</i> &lt; 0.001; BMI 35–39.9 kg/m²: OR 2.67, 95% CI 1.89–3.69, <i>p</i> = 0.002; BMI ≥ 40 kg/m²: OR 3.51, 95% CI 1.24–9.96, <i>p</i> = 0.018), SLD (OR 2.13, 95% CI 1.49–3.05, <i>p</i> &lt; 0.001), moderate alcohol intake (OR 1.36, 95% CI 1.03–1.79, <i>p</i> = 0.031), heavy alcohol intake (OR 4.31, 95% CI 2.90–6.40, <i>p</i> &lt; 0.001), high blood pressure (OR 1.30, 95% CI 1.01–1.67, <i>p</i> = 0.044), and high fasting blood glucose (OR 1.61, 95% CI 1.12–2.28, <i>p</i> = 0.008). In female, only age &gt; 65 years (OR 3.02, 95% CI1.93–4.73, <i>p</i> &lt; 0.001), BMI, and high uric acid (OR 2.06, 95% CI 1.15–3.68, <i>p</i> = 0.015) were extracted. In an obese male, alcohol intake and cardiometabolic factors were associated with liver fibrosis progression based on APRI, independent of elevated BMI and SLD.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirin and NSAIDs are Associated With Reduced Cancer and Mortality Risk in Patients With Chronic Liver Diseases—A Swedish Cohort Study","authors":"Knut Stokkeland,&nbsp;Karin Söderberg-Löfdal,&nbsp;Pär Villner,&nbsp;Johan Franck","doi":"10.1002/lci2.70011","DOIUrl":"https://doi.org/10.1002/lci2.70011","url":null,"abstract":"<p>Aspirin and NSAIDs may be beneficial in chronic liver diseases. We explored the effect of exposure to anti-inflammatory drugs in patients with chronic liver disease with regard to adverse liver events, cancers and mortality. A cohort of patients with chronic liver disease 2005–2020 (<i>n</i> = 21 439) was studied. All patients were hospitalised in Region Stockholm. Data from the Patient Register, Prescribed Drug Register, Death Certificate Register, Cancer Register, two laboratories and Stockholm Center for Health Data were combined. We analysed death, adverse liver events, liver cancers and all cancers in relation to drug exposure. During follow-up 10 279 patients (47.9%) died. There was a reduced risk for all cancers combined when patients were exposed to aspirin (aHR 0.68; 95% CI 0.63–0.73) and NSAIDs (aHR 0.80; 95% CI 0.75–0.86) and a reduced risk of liver cancer in patients exposed to aspirin (aHR 0.48; 95% CI 0.41–0.57) and to NSAIDs (aHR 0.71; 95% CI 0.62–0.82). There was a reduced overall mortality risk for patients exposed to NSAIDs (aHR 0.68; 95% CI 0.64–0.72) and a reduced mortality risk for patients exposed to aspirin (aHR 0.86; 95% CI 0.82–0.91) after adjusting for comorbidities and severity of the liver disease. Patients with alcohol-associated liver disease exposed to aspirin had reduced mortality risk (aHR 0.82; 95% CI 0.76–0.89) and exposure to NSAIDs also reduced the mortality risk (aHR 0.74; 95% CI 0.69–080). Exposure to aspirin or NSAIDs in patients with chronic liver diseases was associated with reduced cancer risks including risk for liver cancer and decreased overall mortality risk.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}