Le Bich Hang Pham, Taeeung Kim, Seoyoung Kim, Yun Seok Kim, Jiyeon Kim, Kyeongseon Kim, Hyeonwoo Lim, Wan Seob Shim, Byoungmo Kim, So-Yeol Yoo, Jae-Young Lee, Murim Choi, Won Kim, Keon Wook Kang, Jeeyeon Lee
Received July 15, 2025 Accepted November 10, 2025 Published online November 17, 2025
Background/Aims Ferroptosis, recently emerged as a new cell death modality characterized by iron-dependent peroxidation of lipids, has been explored in various diseases. However, detection of ferroptosis, particularly in chronic liver disease models, is hampered by the lack of universal ferroptosis markers and limited number of fluorescence sensors for in vivo ferroptosis.
Methods In this study, we developed TTM-4 as a highly sensitive near-infrared (NIR) fluorescent probe to detect ferroptosis.
Results TTM-4 exhibited turn-on fluorescence upon viscosity change, enabling visualization of lipid peroxidation in ferroptotic hepatocytes and liver tissue samples with greater sensitivity than BODIPY 581/591 C11. Time-lapse live-cell imaging of erastin-treated cells revealed real-time lipid peroxidation dynamics involving cytosolic lipid droplets (cLDs), endoplasmic reticulum, and nuclear LDs (nLDs) in a chronological order. Further gene expression analysis of 216 liver tissue samples from the NCBI GEO database showed a significant increase in CIDEC concurrent with TTM-4 fluorescence during progression to metabolic dysfunction-associated steatotic hepatitis (MASH). TTM-4, with its low toxicity and turn-on NIR emission during ferroptosis, also enabled in vivo visualization of ferroptosis in liver injury and metabolic dysfunction-associated steatotic liver disease (MASLD) models.
Conclusions Our findings suggest that TTM-4 enables monitoring of ferroptosis in MASLD and would aid in early MASH diagnosis.
Jonggi Choi, Daniel Fulop, Vy H. Nguyen, Eric Przybyszewski, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G. Simon, Raymond T. Chung
Received July 23, 2025 Accepted November 4, 2025 Published online November 11, 2025
Background and Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of cirrhosis and its complications. Given its close association with type 2 diabetes mellitus (T2DM), evaluating whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) can mitigate the progression of liver fibrosis is clinically important. We examined the association between SGLT2i use and liver fibrosis progression in patients diagnosed with MASLD and T2DM.
Methods We conducted a target trial emulation study using a retrospective, active comparator new-user design among adults with MASLD, T2DM, and low-to-intermediate Fibrosis-4 (FIB-4 ≤2.67) scores who initiated treatment with either SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is) at Mass General Brigham or Asan Medical Center from 2013 to 2023. The primary outcome was the progression to advanced fibrosis (FIB-4 >2.67), confirmed on ≥2 occasions within 1 year. The secondary outcome was the development of major adverse liver outcomes (MALO), including incident cirrhosis, decompensation events, hepatocellular carcinoma, or liver transplantation.
Results Among 16,901 eligible patients, 2,571 propensity score-matched pairs were identified with balanced baseline characteristics. During follow-up (median, 3.7 years), fibrosis progression occurred at a rate of 3.46/100 person-years in SGLT2i users and 4.44 in DPP4i users. SGLT2i use was associated with a lower risk of fibrosis progression (HR, 0.78; 95% CI, 0.67–0.89; p<0.001). No significant difference in MALO incidence was observed. Subgroup analyses showed a consistent association among users of metformin, statins, and aspirin.
Conclusions SGLT2i use was associated with reduced risk of fibrotic progression compared to DPP4i use in adults with MASLD and T2DM.
Background & Aims The first metabolic dysfunction-associated steatotic liver disease (MASLD) drug was approved with an unsatisfactorily small effect size. This study aimed to determine key factors impacting the cost-effectiveness of a new hypothetical metabolic dysfunction-associated steatotic liver disease (MASLD) drug as well as its treatment efficacy.
Methods A Markov model reflecting the natural history of MASLD was developed, incorporating fibrosis progression, cardiovascular disease (CVD) risk, and mortality. Treatment effect of Drug X (with $20,000 of annual cost) was assumed to achieve a ≥1 stage fibrosis regression, with a 25% gap of effect size in regression rate over no treatment in the first year. The incremental cost-effectiveness ratio (ICER) over a 20-year horizon was estimated. And sensitivity analyses were conducted to explore uncertainty and identify influential factors.
Results In the base-case analysis, drug X provided an incremental gain of 1.32 quality-adjusted life years (QALYs) and 1.20 life years (LYs) compared to the no treatment, with an ICER of $68,010/QALY – below the $100,000/QALY willingness-to-pay threshold, indicating that Drug X treatment is cost-effective. Two-way sensitivity analysis further highlighted that the drug should achieve at least a 15% initial regression gap and maintain a minimum 3% sustained durability gap to remain cost-effective. And baseline fibrosis stage distribution also acted as an influencing factor.
Conclusions Long-term sustained durability of the hypothetical drug, patient distribution based on baseline fibrosis stage, as well as initial treatment response rate are key factors that influence the cost-effectiveness of new MASLD drugs.
The knowledge accumulated over the past two decades has revealed that the natural history of metabolic dysfunction-associated steatotic liver disease (MASLD) and the drivers of the disease severity are not only complex but also exhibit variation among patients. This intricate clinical scenario entails major therapeutic and management implications. In this review, we provide a comprehensive examination of recent advancements in our understanding of MASLD heterogeneity, drawing insights from multiomics and panomics studies.
The discussion herein explores the instrumental role of panomics in MASLD research, elucidating the potential for the identification of molecular subtypes that exhibit divergent survival outcomes or heterogeneous responses to various treatments. Furthermore, we provide insights into the challenges in addressing disease heterogeneity and potential solutions. Finally, the most advanced technological advancements and prospective research directions in the domain of MASLD research are delineated, with the objective of facilitating the implementation of personalized diagnosis and interventions.
Jiyi Choi, Moon Gyeong Yoon, Se Ha Jang, Geum Ok Baek, Hyun Sun Jung, Na-Rae Lee, Choong Hwan Lee, Ji Eun Han, Jae Youn Cheong, Jung Woo Eun, Soon Sun Kim
Received May 4, 2025 Accepted October 21, 2025 Published online October 27, 2025
Background/Aims Gut microbiome plays a pivotal role in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, yet, associated functional mechanisms and host responses of specific microbial species remain insufficiently characterized. This study investigated the Bacteroides eggerthii therapeutic effects on MASLD by integrating multi-omics analysis and experimental validation in a Western diet-induced mouse model.
Methods Candidate strains were identified using 16S rRNA gene sequencing of fecal samples from individuals with and without MASLD or obesity. B. eggerthii, a species significantly depleted in both groups, was selected for functional evaluation. Male C57BL/6J mice were fed a Western diet (WD) or WD supplemented with B. eggerthii (WD+B) for 12 weeks. Liver histology, serum biochemistry, fecal microbiome and metabolome profiling, and hepatic and intestinal transcriptomic analyses were performed. Anti-steatotic effects of B. eggerthii–derived metabolites were validated in vitro.
Results Bacteroides eggerthii supplementation significantly improved liver weight, inflammation, fibrosis, and steatosis in WD+B group compared to WD alone. PICRUSt-based LEfSe analysis revealed choloylglycine hydrolase activity enrichment in gut microbiota, and strain-specific qPCR confirmed colonization in mouse colon. Integrated transcriptomic analyses revealed lipid and bile acid signaling pathway restoration, including CD36, FXR, and FGF15. Untargeted metabolomics identified elevated 2-hydroxyisocaproic acid (HICA) as a strain-derived metabolite in feces and B. eggerthii culture supernatants. In vitro, HICA significantly reduced lipid accumulation in free fatty acid-induced steatosis models.
Conclusion Bacteroides eggerthii ameliorates MASLD via gut-liver axis modulation, including bile acid metabolism and hepatic lipid signaling. These underscore its therapeutic potential and highlight HICA as a novel microbiome-derived metabolite with anti-steatotic activity.
Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) may progress to liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. So far, genome-wide association studies explain a small fraction of MASLD heritability.
Methods We sought to identify novel genetic determinants of MASLD by exploring interactions between genetic variants and body mass index (BMI). First, we examined genome-wide interactions with BMI for circulating alanine aminotransferase (ALT) levels using UK Biobank data. For identified loci, we next examined associations with hepatic proton density fat fraction (PDFF) in 35,146 independent UK Biobank participants. Associations with PDFF were replicated in four independent European cohorts, followed by a phenome-wide association study. Finally, we used human liver epigenomic maps and CRISPR/Cas9 experiments in vitro and in vivo to functionally characterize the CYP7A1 locus.
Results Thirteen loci interact with BMI for ALT (P<5E-8), including eight well-known genetic modulators of MASLD. Two loci—UBXN2B/CYP7A1 and GIPR—are additionally associated with PDFF. For the intronic rs34783010 in GIPR, the minor T allele is associated with lower BMI and higher HbA1c and liver triglyceride content in humans. The UBXN2B/CYP7A1 locus is associated with PDFF in four additional European cohorts. Epigenomic data and in vitro experiments in human liver cells prioritise rs10504255 and CYP7A1 as the functional effectors in this locus. Perturbation of CYP7A1 orthologues using CRISPR/Cas9 results in less liver fat in 10-day-old, metabolically challenged zebrafish larvae.
Conclusions A genome-wide single nucleotide polymorphism×BMI design fuelled identification of two MASLD genes: CYP7A1 and GIPR.
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Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic. The disease has a strong genetic component, and a common missense variant (rs2642438) in the mitochondrial amidoxime-reducing component 1 (MARC1) gene confers protection against its onset and severity. However, there are contrasting results regarding the mechanisms that promote this protection.
Methods We downregulated MARC1 in primary human hepatocytes (PHHs) using short interfering RNA (siRNA). We measured neutral lipid content by Oil-Red O staining and fatty acid oxidation by radiolabeled tracers. We also performed RNA-sequencing and proteomic analysis using LC-MS. Additionally, we analyzed data from 239,075 participants from the UK Biobank.
Results Downregulation of MARC1 reduced neutral lipid content in PHHs homozygous for the wild type (p.A165, risk), but not for the mutant (p.T165, protective), allele. We found that this reduction was mediated by increased fatty acid utilization via β-oxidation. Consistent with these results, we found that the levels of 3-hydroxybutyrate, a by-product of β-oxidation, were higher in carriers of the rs2642438 minor allele among samples from the UK biobank, indicating higher β-oxidation in these individuals. Moreover, downregulation of the MARC1 p.A165 variant resulted in a more favorable phenotype by reducing ferroptosis and reactive oxygen species levels.
Conclusions MARC1 downregulation in carriers of the risk allele results in lower hepatocyte neutral lipids content due to higher β-oxidation, while upregulating beneficial pathways involved in cell survival.
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Background/Aims Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.
Methods Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.
Results The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4–36.7). Within this category, the age-adjusted prevalence for MASLD was 31.9% (95% CI 30.4–33.4), MetALD 2.2% (95% CI 1.8–2.6), and ALD 0.8% (95% CI 0.6–1.1). The prevalence of SLD and MASLD showed a statistically insignificant decrease during COVID-19, while ALD increased without significance. In contrast, the prevalence of advanced fibrosis in SLD was significantly higher during the COVID-19 era, at 9.8% for 285 dB/m and 7.8% for 263 dB/m, compared to 7.4% (P=0.039) and 6% (P=0.041) in the pre-COVID-19 era. The proportion of advanced fibrosis and cirrhosis in individuals with ALD was two-fold higher than MASLD and MetALD, largely due to increases during the COVID-19 era.
Conclusions While the prevalence of SLD and its subcategories remained stable, there was a significant increase in advanced fibrosis among SLD individuals during the COVID-19 era, with ALD having a proportion of advanced fibrosis and cirrhosis that was twice as high as MASLD and MetALD.
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One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD)―formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study’s comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals’ unique risks.
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Background/Aims Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis.
Methods Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis.
Results There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts.
Conclusions This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.
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As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%. Although MASLD does not always develop into progressive liver disease, it has become the top indication for liver transplant in the United States for women and those with hepatocellular carcinoma (HCC). Nonetheless, the most common cause of mortality among patients with MASLD remains cardiovascular disease. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with an increased risk of developing de novo T2D, chronic kidney disease, sarcopenia, and extrahepatic cancers. Furthermore, MASLD is associated with decreased health-related quality of life, decreased work productivity, fatigue, increased healthcare resource utilization, and a substantial economic burden. Similar to other metabolic diseases, lifestyle interventions such as a heathy diet and increased physical activity remain the cornerstone of managing these patients. Although several obesity and T2D drugs are available to treat co-morbid disease, resmetirom is the only MASH-targeted medication for patients with stage 2–3 fibrosis that has approved by the Food and Drug Administration for use in the United States. This review discusses MASLD epidemiology and its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD incidence could continue to increase.
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Advances in understanding the mechanism of noncoding RNA (ncRNA)-mediated regulation of macrophage polarization in NAFLD Chang Ge, Yi Yuan, Xiaoning Li, Jianmin Zhang, Jitao Ling, Xuehong Zheng, Yuting Wu, Xin Huang, Pingping Yang, Xiao Liu, Deju Zhang, Jianping Liu, Jing Zhang, Peng Yu Biochemical Pharmacology.2025; 242: 117372. CrossRef
Association of serum trace elements with non-invasive fibrosis scores in metabolic dysfunction-associated steatotic liver disease Erfan Banisefid, Sahand Karkon Zonouzi, Sina Hamzehzadeh, Zeinab Nikniaz, Seyedehyasmin Moghaddamziabari, Leila Alizadeh Scientific Reports.2025;[Epub] CrossRef
Metabolic dysfunction-associated steatotic liver disease: epidemiological trends, risk factors, and the role of gut microbiota in disease progression (a literature review) А.А. Antoniv, L.V. Kanovska, O.V. Kaushanska, Yu.M. Yarinich INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2025; 21(6): 656. CrossRef
Preventing false positive imaging diagnosis of HCC: differentiating HCC from mimickers and practical strategies Ijin Joo Journal of Liver Cancer.2025; 25(2): 217. CrossRef
Real-World Lifestyle Interventions are a Practical Model to Improve Liver Stiffness Christopher Kasia, Mary Rinella Journal of Clinical and Experimental Hepatology.2025; 15(6): 103201. CrossRef
Pubertal exposure to glyphosate-based herbicide aggravates diet-induced steatosis and hormonal dysregulation in adult mice Jakeline Liara Teleken, Ana Paula Farina Rosolen, Joseane Morari, Sandra Lucinei Balbo, Rosane Aparecida Ribeiro, Maria Lúcia Bonfleur Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub] CrossRef
Reliable Monitoring of Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease Using Imaging: A Systematic Literature Review and Meta-Analysis on Measurement Repeatability Michael Ndaa, Prashant K. Pandya, Jordan Swensson, Niharika Samala, Saima Ajaz, Deepak Joshi, Walid S. Ayoub, Fatih Akisik Endocrine Practice.2025;[Epub] CrossRef
The effects of different exercise intensities on body composition and cardiovascular risk indicators in children with metabolic syndrome: a RCT network meta-analysis Yimin Hu, Juan Ouyang, Yi Xia, Yi Sheng BMC Sports Science, Medicine and Rehabilitation.2025;[Epub] CrossRef
Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies Sana Raza, Rukshana Mahamood, Pratik Medhe, Ambuj Shahi, Abhishek Yadav, Archana Tewari, Rohit A. Sinha npj Metabolic Health and Disease.2025;[Epub] CrossRef
Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction Wooyoung Choi, Gun Ha Woo, Tae-Hwan Kwon, Jae-Han Jeon International Journal of Molecular Sciences.2025; 26(19): 9715. CrossRef
Immunosenescence and metabolic reprogramming in MASLD: an age-dependent immunometabolic vicious cycle and therapeutic opportunities Yuxin Xu, Qiuxiang Li, Xuehua Jiao Frontiers in Cell and Developmental Biology.2025;[Epub] CrossRef
Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease Ralf Weiskirchen, Amedeo Lonardo International Journal of Molecular Sciences.2025; 26(19): 9594. CrossRef
Comparative effectiveness of GLP-1 receptor agonists and dual agonists in the treatment of patients with metabolic dysfunction associated steatohepatitis: a systematic review and meta-analysis Meng Li, Jianli Hu, Yip Han Chin, Han Shi Jocelyn Chew, Wenru Wang Frontiers in Endocrinology.2025;[Epub] CrossRef
Investigation of the Effect of Isotonic Drinks on Quantitative MRI Markers of the Liver and Spleen Natassa N. Pittas, Michael Pavlides, Ferenc E. Mózes NMR in Biomedicine.2025;[Epub] CrossRef
Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease Zhili Cheng, Magdalene K Montgomery Clinical Science.2025; 139(19): 1095. CrossRef
Naringin mitigates liver damage in a tissue-engineered liver of metabolic dysfunction-associated steatotic liver disease model by promoting autophagy via the mTOR-ULK1 pathway Jihui Jia, Yizhi Zhang, Jing Lin, Zhongping Duan, Yu Chen, Xiaohui Zhang Molecular Biology Reports.2025;[Epub] CrossRef
Dietary supplementation with a designer metabolic modulator improves MASLD and associated anxiety in mice Agnese Segala, Gaia Favero, Emanuela Bottani, Alice Vetturi, Emirena Garrafa, Edoardo Parrella, Chiara Ruocco, Maurizio Ragni, Rita Rezzani, Enzo Nisoli, Alessandra Valerio Frontiers in Pharmacology.2025;[Epub] CrossRef
From Steatosis to Immunosenescence: The Impact of Metabolic Dysfunction on Immune Aging in HIV and Non-HIV Populations Carlo Acierno, Maria Frontuto, Giulio Francesco De Stefano, Ana Erezanu, Andrea Limone, Simona Morella, Francesco Picaro, Donatella Palazzo, Michele Gilio Biomedicines.2025; 13(10): 2513. CrossRef
Linear association between the composite dietary antioxidant index and the prevalence of sarcopenia in metabolic dysfunction-associated steatotic liver disease Jue Zhang, Huan Shi Lipids in Health and Disease.2025;[Epub] CrossRef
Research trends on the quality of life in patients with metabolic dysfunction-associated fatty liver diseases: a scientific metrology study Can Huang, Meng Chen, Yanfang Sun, Lin Zhang, Wei Liu Frontiers in Nutrition.2025;[Epub] CrossRef
2025 Clinical Practice Guidelines for Diabetes: Management of Metabolic Dysfunction-Associated Steatotic Liver Disease Jaehyun Bae The Journal of Korean Diabetes.2025; 26(3): 172. CrossRef
Pharmacotherapy of the metabolically associated fatty liver disease E.E. Mulyukova, E.L. Novikova, I.A. Skirdov, K.S. Usmanova, N.V. Yusifzade Russian Journal of Preventive Medicine.2025; 28(10): 103. CrossRef
Proton Density Fat Fraction and Its Role in Prediction of Metabolic Dysfunction Scott B. Reeder, Jitka Starekova Radiology.2025;[Epub] CrossRef
Coffee and Tea Intake Is Inversely Associated With Hepatic Fat Deposition, Iron Deposition, and Fibroinflammation in the General Population Zhuoshuai Liang, Xiaoyue Sun, Huizhen Jin, Wenhui Gao, Xinmeng Hu, Yi Cheng, Jikang Shi, Yawen Liu Molecular Nutrition & Food Research.2025;[Epub] CrossRef
Hydroxytyrosol Improves Metabolic Dysfunction-Associated Fatty Liver Disease Dependent on the Modulation of Gut Microbiota Yuji Xiao, Xue Zhang, Bing Shao, Ziyi Wu, Xiao Li, Dongxin Yi, Tao Li, Tao Yang, Jiaxin Zhu, Tiecheng Huang, Yixue Deng, Tianming Qiu, Guang Yang, Xiance Sun, Ningning Wang Journal of Agricultural and Food Chemistry.2025; 73(43): 27450. CrossRef
Hepatocellular carcinoma: modern aspects of interdisciplinary management. Part 1. Epidemiology, risk factors, diagnosis Yu.M. Stepanov, N.Yu. Zavhorodnia, O.M. Vlasova GASTROENTEROLOGY.2025; 59(3): 206. CrossRef
CT-Based Radiomic Models in Biopsy-Proven Liver Fibrosis Staging: Direct Comparison of Segmentation Types and Organ Inclusion Andreea Mihaela Morariu-Barb, Tudor Drugan, Mihai Adrian Socaciu, Horia Stefanescu, Andrei Demirel Morariu, Monica Lupsor-Platon Diagnostics.2025; 15(21): 2671. CrossRef
Liver-Related COVID-19 Consequences: Dynamics of Liver Health in 2.5 Years Ieva Vanaga, Oksana Kolesova, Aleksandrs Kolesovs, Maija Radzina, Davis Simanis Putrins, Jelena Egle, Sniedze Laivacuma, Jelena Storozenko, Ludmila Viksna Journal of Clinical Medicine.2025; 14(21): 7604. CrossRef
Metabolic dysfunction–associated steatotic liver disease alters brain function and behavior: Insights from liver-targeted siRNA therapy Teresa Cardoso Delgado, Celia Martín-Cuevas, Ana C. Sánchez Hidalgo, Antonio Gil Gómez, Claudia M. Rejano Gordillo, Jon Landa, Rocío Gallego Durán, Naroa Goikoetxea-Usandizaga, Irene González-Recio, Clàudia Gil-Pitarch, L. Estefanía Zapata-Pavas, Jon Ande Science Advances.2025;[Epub] CrossRef
Association of Diet Quality, Dietary Acid Load, and Dietary Antioxidant Index With Cardiometabolic and NAFLD Risk Factors Among Patients With Metabolic Syndrome: A Cross‐Sectional Study Bijan Ghobadian, Seyedeh Atiye Shahrokhi, Saman Rezaei Talabon, Vahid Notash, Fatemeh Maleki Sedgi, Mehran Rahimlou Food Science & Nutrition.2025;[Epub] CrossRef
Quantitative Approaches to Accelerate MASH Drug Discovery and Development Yasmeen Abouelhassan, Shailendra Tallapaka, Ramin Mehrani, Scott Q. Siler, Li Qin, Zeyuan Wang, Maria E. Trujillo Clinical Pharmacology & Therapeutics.2025; 118(6): 1378. CrossRef
Mitochondrial transplantation and platelet rich plasma for the treatment of non-alcoholic fatty liver disease Manuel Alejandro Vargas-Vargas, Marcela González-Montoya, Olin Torres-Isidro, Omar Ortiz-Avila, Elizabeth Calderón-Cortés, Christian Cortés-Rojo World Journal of Hepatology.2025;[Epub] CrossRef
Repurposing levothyroxine for managing metabolic dysfunction-associated steatotic liver disease Leonidas H. Duntas, Stergios A. Polyzos, Ulrike Gottwald-Hostalek, Bogumila Urgatz, Paul M. Yen Endocrine.2025;[Epub] CrossRef
Genetic polymorphisms associated with metabolic dysfunction-associated steatotic liver disease and cardiometabolic risk susceptibility in the Chinese Han population Mingjia Dai, Yan Li, Jing Zhang, Yuhua Ruan, Ye Liu, Jungui Hao, Fang Ji, Xuebing Yan Human Genomics.2025;[Epub] CrossRef
Lipid-lowering mechanism of Swietenia macrophylla king leaves through SREBP-1c/FASN axis and RNA sequencing validation Yingwei Liu, Yunpeng Sun, Ting Zhou, Xiao Huang, Guokai Wang, Lijuan Sun Food Bioscience.2025; 74: 107860. CrossRef
Reconsidering Cardiovascular Risk Assessment in Patients With MASLD Ming Hou Liver International.2025;[Epub] CrossRef
From steatosis to cirrhosis: the role of obesity in the progression of liver disease Klaudia Nowak, Maria Paluch, Maja Cudzik, Klaudia Syska, Wiktoria Gawlikowska, Jakub Janczura Journal of Diabetes & Metabolic Disorders.2025;[Epub] CrossRef
Triglyceride-cholesterol-body weight index associated with the risk of metabolic dysfunction-associated steatotic liver disease: a population-based cross-sectional study Li Fan, Yongkang Su, Yue Chen, Ling Xu, Hairong Huang, Chunsheng Lu, Jia Peng, Yingbin Sun, Min Jia Frontiers in Nutrition.2025;[Epub] CrossRef
Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism Rosellina M. Mancina, Luca Valenti, Stefano Romeo Nature Metabolism.2025; 7(11): 2199. CrossRef
The transition from NAFLD to MASLD: implications for Diagnosis, Prognosis, and Clinical Management Carlo Acierno, Riccardo Nevola, Fannia Barletta, Katarzyna Zielińska, Luca Rinaldi, Ferdinando Carlo Sasso, Caterina Conte, Luigi Elio Adinolfi, Alfredo Caturano Exploration of Medicine.2025;[Epub] CrossRef
The effects of salvia hispanica (chia seeds) on insulin sensitivity, hematological inflammatory indices and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD) Sara Arefhosseini, Maryam Parimi, Helda Tutunchi, Mehrangiz Ebrahimi-Mameghani Nutrition & Metabolism.2025;[Epub] CrossRef
Prevalence and Risk Factors of Metabolic Dysfunction–Associated Steatotic Liver Disease in Patients With Type 2 Diabetes Mellitus at a Tertiary Center in Saudi Arabia: Cross-Sectional Questionnaire Study Abdulrahman M Elnasieh, Mohammed Almesned, Akram N Al Hazmi, Atheer Alturki, Faisal I Alhawaidi, Razan K Alhadlq, Maryam Alramadhan, Nasser Alobilan, Yasser Sheikh Qroosh JMIR Diabetes.2025; 10: e77772. CrossRef
Differentiating MASL and MASH: Clinical Insights from Comparative Case Reports in MASLD Chang-Gue Son The Journal of Internal Korean Medicine.2025; 46(4): 954. CrossRef
Multi-omics analysis elucidates the therapeutic mechanisms of the Quzhi formula in metabolic dysfunction-associated steatohepatitis targeting gut microbiota, lipid metabolism, and the role of its metabolite fraxin Jiao-Xiang Wu, Yue-Lan Wu, Mei-Fang Li, Nian Liu, Ying Liu, Yan-Ping Huang, Yuan Gan, Xiao-Yu Wang, Hai-Sheng Chai, Jin Xu, Qian Xi, Xi-Rong Guo, Hui-Ming Sheng, Ting-Ting Shen, Qin Zhang Frontiers in Pharmacology.2025;[Epub] CrossRef
Implications of the Liver-Gut Axis in Liver Disease: From Mechanisms to Therapeutic Targets Mariana M. Ramírez-Mejía, Guadalupe Ponciano-Rodríguez, Nahum Méndez-Sánchez Archives of Medical Research.2025; 56(8): 103335. CrossRef
Herbal Medicine for Metabolic Dysfunction-Associated Steatotic Liver Disease: Clinical Effectiveness and Research Trends - A Systematic Review and Meta-Analysis Min-jo Seo, Su-na Park, Ji-won Lee, So-rim Kim, Jin-hyun Kim, Min-ji Sun, Geon-sik Kong, Yo-sup Choi The Journal of Internal Korean Medicine.2025; 46(4): 774. CrossRef
Primary Human Tissue Models for Metabolic Dysfunction‐Associated Liver Disease ‐ toward Streamlining Drug Discovery with Patient‐Derived Assays Sonia Youhanna, Nayere Taebnia, Yingxin Liang, Ningtao Cheng, Yi Wang, Maurice Michel, Volker M. Lauschke Advanced Biology.2025;[Epub] CrossRef
The Impact of Liraglutide on Patients With Metabolic Dysfunction–Associated Steatotic Liver Disease Jae Eun So, Jaehong Jeong, Jung Pyo Hong, Dong Yun Kim, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Hye Won Lee, Seung Up Kim Journal of Gastroenterology and Hepatology.2025; 40(12): 2976. CrossRef
Remnant cholesterol, low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease in metabolic dysfunction-associated steatotic liver disease: a cohort study Di Zhou, Mengge Zhou, Shuohua Chen, Chenlu Yang, Yanhong Wang, Yang Zhou, Shutong Wu, Shouling Wu, Li Wang Lipids in Health and Disease.2025;[Epub] CrossRef
Diabetes and the Liver E. Dadey, TY Lim, J Makaronidis Clinical Medicine.2025; : 100528. CrossRef
Effects of long working hours on metabolic dysfunction-associated steatotic liver disease, with and without increased alcohol intake, in healthy workers: A 10-year cohort study Yesung Lee, Woncheol Lee, Anna Di Sessa PLOS One.2025; 20(11): e0336569. CrossRef
Association between longitudinal weight change and clinical outcome in individuals with MASLD Yu Shi, Ruoqi Zhou, Seung Up Kim, Terry Cheuk-Fung Yip, Emmanuel Tsochatzis, Salvatore Petta, Atsushi Nakajima, Hannes Hagström, Elisabetta Bugianesi, Wah-Kheong Chan, Jérôme Boursier, Boon-Bee George Goh, Arun J. Sanyal, Manuel Romero-Gomez, José Luis Ca Hepatology.2025;[Epub] CrossRef
Valproic Acid Exacerbates Lipid Accumulation in High‐Fat Hepatocytes Induced by Oleic Acid: Insights From Lipidomic Analysis Shansen Xu, Xianglei Ma, Lingli Huang, Tingting Yue, Ya'nan Chen Lipids.2025;[Epub] CrossRef
Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher JAMA.2025;[Epub] CrossRef
Recognizing the Burden of Metabolic Liver Disease in IBD Raseen Tariq, Richard K Sterling Inflammatory Bowel Diseases.2025;[Epub] CrossRef
Safety and efficacy of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis (IMPACT): 24-week results from a multicentre, randomised, double-blind, phase 2b study Mazen Noureddin, Stephen A Harrison, Rohit Loomba, Naim Alkhouri, Naga Chalasani, Muhammad Y Sheikh, Shaheen Tomah, Julio A Gutierrez, Silvia Urbina, John J Suschak, Randy Brown, Ozioma Odili, Jay Yang, Stephine Keeton, Guy Neff, Edward Mena, M Scot Rober The Lancet.2025;[Epub] CrossRef
Impact of Metabolic Dysfunction-Associated Steatotic Liver Disease on Fatigue and Pruritus in Primary Sclerosing Cholangitis: A U.S. Single-Center Study Natalia Rojas-Amaris, Ana Marenco-Flores, Carmen Lara-Romero, Romelia Barba, Denisse Rubio-Cruz, Ximena Parraga, Daniela Goyes, John Esli Medina-Morales, Leandro Sierra, Manuel Romero-Gomez, Michelle Lai, Behnam Saberi, Vilas Patwardhan, Alan Bonder Journal of Clinical Medicine.2025; 14(22): 8083. CrossRef
Editorial: Understanding How Social Determinants of Health Impact Mortality in MASLD—Insights From a National Analysis Joyce Lui, Yesung Kweon, Mohamed I. Elsaid Alimentary Pharmacology & Therapeutics.2025;[Epub] CrossRef
Personalized management of metabolic dysfunction-associated steatotic liver disease Zhen Sun, Kui Ming Chan, Haojie Jin iLIVER.2025; 4(4): 100207. CrossRef
Advances in Incretin‐Based Therapies for MAFLD: Mechanisms and Clinical Evidence Wenqi Dong, Haiming Zhang, Shaowei Mu, Shuyi Shi, Junli Zhang, Keshu Xu Clinical Pharmacology & Therapeutics.2025;[Epub] CrossRef
Beyond Discrete Diagnoses: Conceptualizing Obesity-associated Metabolic Disorders as a Unified, Dynamic Continuum Cong Xie, Yulian Yuan, Yunjing Wang, Cong Qi, Wei Wang, Chuan An, Aifeila Aikepaer, Yaofu Zhang, Ge Zhang, Xingzhong Feng, Huijuan Gao Current Obesity Reports.2025;[Epub] CrossRef
Immunotherapy versus lenvatinib in advanced hepatocellular carcinoma: The critical role of subgroup analyses Tingfeng Huang, Jiahao Law, Ningqi Pang, Shichuan Tang iLIVER.2025; 4(4): 100208. CrossRef
Plasma Extracellular Vesicles Contain Protein Biomarkers for Capturing Stages of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Preliminary Exploratory Study Yakun Li, Koen C. van Son, Sandra Serna-Salas, Justina C. Wolters, Nienke P. M. Wassenaar, Stan Driessen, Anne Linde Mak, Anne-Marieke van Dijk, Veera A. T. Houttu, Julia J. Witjes, Diona Zwirs, Michail Doukas, Joanne Verheij, Robin P. F. Dullaart, Hans B Biomolecules.2025; 15(11): 1596. CrossRef
Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD): Mechanisms, Clinical Implications and Therapeutic Advances Dalia M. Miller, Kiana F. McCauley, Kimberly J. Dunham‐Snary Endocrinology, Diabetes & Metabolism.2025;[Epub] CrossRef
Liver Transplantation in the Era of Metabolic Dysfunction–Associated Fatty Liver Disease: Challenges, Ethical Dilemmas, and Future Directions Said A. Al-Busafi, Mohammed Eslam Transplantology.2025; 6(4): 35. CrossRef
The albumin-to-creatinine ratio predicts and explores potential mediation of mortality in metabolic dysfunction-associated steatotic liver disease in U.S. adults: evidence from NHANES 1999–2018 Huanjie Zhou, Hao Huang, Huiliu Zhao, Naiqi Pang, Meifang Huang, Chao Ou, Ming Lao BMC Gastroenterology.2025;[Epub] CrossRef
Effects of bariatric surgery on neurological disturbances and quality of life in patients with metabolic dysfunction-associated steatotic liver disease and obesity: a prospective longitudinal study Concepción Gómez, Juan José Gallego Roig, María Lapeña, Clara Alfaro-Cervelló, Alessandra Fiorillo, Adrià López-Gramaje, Raquel Alfonso Ballester, Norberto Casinello, María Capilla Lozano, María Desamparados Escudero-García, Cristina Montón, Amparo Urios Surgery for Obesity and Related Diseases.2025;[Epub] CrossRef
Effect of Weight Loss on Clinical Outcomes in Patients With Chronic Gastrointestinal and Liver Diseases Nicola Pugliese, Matteo Spertino, Miriana Mercurio, Stefano Ciardullo, Gianluca Perseghin, Cesare Hassan, Roberto Vettor, Salvatore Petta, Alessio Aghemo Clinical Gastroenterology and Hepatology.2025;[Epub] CrossRef
Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice Yuxuan Chen, Chendong Liu, Qian Yang, Jingtao Yang, He Zhang, Yong Zhang, Yanruyu Feng, Jiaqi Liu, Lian Li, Dapeng Li Journal of Pharmaceutical Analysis.2025; 15(11): 101273. CrossRef
К эпидемиологии жировой болезни печени, связанной с метаболической дисфункцией (систематический обзор литературы)
Вера Людвиговна Грицинская, Валерия Павловна Новикова Children's medicine of the North-West.2025; 13(3): 108. CrossRef
The shifting burden of gastrointestinal and liver diseases in Southeast Asia and effective control strategies
An umbrella meta-analysis of microbial therapy on hepatic steatosis, fibrosis, and liver stiffness in metabolic dysfunction-associated steatotic liver disease Gvzalnur Kurban, Xiangjun Chen, Xingyi Jin, Hui Xia, Shaokang Wang, Guiju Sun Frontiers in Nutrition.2025;[Epub] CrossRef
Linking bisphenol a exposure to MASLD: insights from network toxicology and machine learning based on NHANES 2005–2012 data Jiaquan Yuan, Haoyang Xu, Junhong Gan, Haiyan Zhao Toxicology Research.2025;[Epub] CrossRef
Curcumin and Tetrahydrocurcumin as Multi-Organ Modulators of the Adipose Tissue–Gut–Liver Axis: Mechanistic Insights, Therapeutic Potential, and Translational Challenges Marina Konaktchieva, Radoslav Stojchevski, Nikola Hadzi-Petrushev, Hristo Gagov, Rositza Konakchieva, Vadim Mitrokhin, Gjoko Kungulovski, Mitko Mladenov, Dimiter Avtanski Pharmaceuticals.2025; 18(12): 1791. CrossRef
Ten-Year Atherosclerotic Cardiovascular Disease Risk in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Separate Analyses from Romanian and Italian Cohorts Integrating Metabolic, Hepatic, and Gut–Liver Axis Markers Naomi-Adina Ciurea, Cristina Monica Pantea, Paul Grama, Irina-Bianca Kosovski, Ilaria Farella, Simona Bataga, Agostino Di Ciaula, Piero Portincasa Journal of Clinical Medicine.2025; 14(23): 8361. CrossRef
Ultra-processed food consumption and the risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD): a five-year prospective cohort study in Iranian adults Omid Emami, Ali Nikparast, Matin Sepehrinia, Saeid Hadi, Jalaledin Mirzay Razzaz, Reza Homayounfar Journal of Health, Population and Nutrition.2025;[Epub] CrossRef
MASLD: Lipotoxicity and Imaging Parallels from Liver Steatosis to Kidney Injury Sarmis Marian Săndulescu, Denisa Ștefania Ghiga, Diana Rodica Tudorașcu, Daniela Larisa Săndulescu, Adrian Mită, Marinela Cristiana Urhuț, Citto-Iulian Taisescu Life.2025; 15(12): 1805. CrossRef
NAD + in fatty liver disease: mechanistic insights and associated targets Yaxin Guo, Yuting Wang, Shiran Wu, Yong Wang, Xinde Liu Cell Biology and Toxicology.2025;[Epub] CrossRef
The impact of high fructose corn syrup on liver injury and glucose metabolism: a systematic review Zane Z. Yu, Sneha Varahala, Sean L. C. Lim, Maimuna C. Marenah, Julia Wattacheril Frontiers in Nutrition.2025;[Epub] CrossRef
Association Between Subclinical Hypothyroidism and MASLD: A Systematic Review and Meta‐Analysis Gedion Yilma Amdetsion, Chun-Wei Pan, Hiwot Tebeje, Abhin Sapkota, Shreyas Nandyal, Vikram Kotwal, Fortofoiu Mircea-Catalin International Journal of Hepatology.2025;[Epub] CrossRef
Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis Chun-Ye Zhang, Shuai Liu, Yu-Xiang Sui, Ming Yang World Journal of Hepatology.2025;[Epub] CrossRef
Liver fibrosis index and mortality in metabolic dysfunction–associated steatotic liver disease: a Korean cohort study Yesung Lee, Woncheol Lee Scientific Reports.2025;[Epub] CrossRef
Macrophage-tregs crosstalk: the “hub” of the immune network in MASLD Huihui Zhao, Weili Wang, Pengchao Zhu, Zhaohong Shi Frontiers in Immunology.2025;[Epub] CrossRef
Proteolysis targeting chimera degraders target pseudokinases to treat metabolic dysfunction-associated steatohepatitis and fibrosis: Mechanisms and therapeutic insights Yibing Wang, Jiajing Peng Pharmacological Research.2025; : 108054. CrossRef
Novel dual AMPK/NRF2 activation by leucocyanidin from Hawthorn (Crataegus) for mitochondria repair-Targeted therapy of hepatic steatosis Yunheng Li, Minghua Ye, Qiaojun He, Bo Yang, Peihua Luo, Xiaochun Yang Phytomedicine.2025; : 157614. CrossRef
The role of liver sinusoidal endothelial cells in liver diseases: Key players in health and pathology Eric Felli, Yeldos Nulan, Martí Ortega-Ribera, Anabel Fernández-Iglesias, Jordi Gracia-Sancho Journal of Hepatology.2025;[Epub] CrossRef
A comparative study between ultrasound-guided-attenuation-parameter (UGAP), controlled attenuation parameter (CAP), and proton density fat fraction (PDFF) for assessment of hepatic steatosis Marie Byenfeldt, Christer Grönlund, Patrik Nasr, Anna Lindam, Mattias Ekstedt, Peter Lundberg, Johan Kihlberg Scandinavian Journal of Gastroenterology.2025; : 1. CrossRef
Metabolic dysfunction-associated steatotic liver disease is associated with androgenetic alopecia in adults with stronger effects in women and unhealthy lifestyles Sina Bazmi, Mohammad Saeed Soleimani-Meigoli, Mohammadreza Fardaei, Zahra Mohammadi, Reza Homayounfar, Maryam Kazemi, Babak Pezeshki, Mojtaba Farjam Scientific Reports.2025;[Epub] CrossRef
Kidney function mediates the association of per- and poly-fluoroalkyl substances (PFAS) and heavy metals with hepatic fibrosis risk Zhengqi Wei, Jincheng Liu, Na Wang, Keke Wei Environmental Research.2024; 263: 120092. CrossRef
Assessing Mortality Disparities Among Non-Alcoholic Fatty Liver Disease Metabolic Dysfunction Fatty Liver Disease and Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Meta-Analysis Fahad Lakhdhir, Agha Syed Muhammad, Ahmed Nasir Qureshi, Imran A Shaikh, Imran Joher, Jawaria Majeed, Javaria Khan Cureus.2024;[Epub] CrossRef
Leukocyte telomere shortening in metabolic dysfunction-associated steatotic liver disease and all-cause/cause-specific mortality Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed Clinical and Molecular Hepatology.2024; 30(4): 982. CrossRef
Understanding the epidemiology of metabolic dysfunction-associated steatotic liver disease is essential for its management: need for attention to accurate diagnostic coding and classification Han Ah Lee The Korean Journal of Internal Medicine.2024; 39(6): 869. CrossRef
AI in Hepatology: Revolutionizing the Diagnosis and Management of Liver Disease Sheza Malik, Rishi Das, Thanita Thongtan, Kathryn Thompson, Nader Dbouk Journal of Clinical Medicine.2024; 13(24): 7833. CrossRef
Small intestinal bacterial overgrowth and metabolic dysfunction-associated steatotic liver disease Ziteng Wang, Wentao Tan, Jiali Huang, Qian Li, Jing Wang, Hui Su, Chunmei Guo, Hong Liu Frontiers in Nutrition.2024;[Epub] CrossRef
Comparisons of Post-Load Glucose at Different Time Points for Identifying High Risks of MASLD Progression Long Teng, Ling Luo, Yanhong Sun, Wei Wang, Zhi Dong, Xiaopei Cao, Junzhao Ye, Bihui Zhong Nutrients.2024; 17(1): 152. CrossRef
The Ovary–Liver Axis: Molecular Science and Epidemiology Ralf Weiskirchen, Amedeo Lonardo International Journal of Molecular Sciences.2025; 26(13): 6382. CrossRef
Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease Ralf Weiskirchen, Amedeo Lonardo International Journal of Molecular Sciences.2025; 26(19): 9594. CrossRef
Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel drug discovery Stavros P. Papadakos, Chara Georgiadou, Eva Kassi, Rallia-Iliana Velliou, Antonios Chatzigeorgiou Expert Opinion on Drug Discovery.2025; : 1. CrossRef
Background/Aims Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution.
Methods We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure.
Results There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, P<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, P<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, P<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, P<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (P=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; P<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; P<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; P=0.01), were independently associated with MASLD development after HCV cure.
Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.
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Background/Aims Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD.
Methods Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing.
Results Methylome and transcriptome analyses of liver biopsies revealed significant (P<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA, and SERPING1, as well as hypomethylation (P<0.0005) and upregulation (P<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data.
Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.
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Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
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