Hepatology Communications最新文献

{"title":"The Transitional Liver Clinic: Study protocol for a stepped-wedge cluster randomized trial.","authors":"Lindsay Yoder, Elliot B Tapper, Richard Kalman, Mary Rinella, Nicole Bendin, Manisha Verma, Francis Pike, Naga Chalasani, Neha Nalumasu, Eric S Orman","doi":"10.1097/HC9.0000000000000990","DOIUrl":"10.1097/HC9.0000000000000990","url":null,"abstract":"<p><strong>Background: </strong>Patients with complications of advanced liver disease experience high rates of hospital readmission after discharge. Transitional care models have improved outcomes in other chronic conditions, but their efficacy in liver disease care remains uncertain. This randomized trial evaluates the effectiveness of a tailored transitional care model-the Transitional Liver Clinic (TLC)-in reducing readmissions, improving quality of life, and enhancing patient satisfaction for patients with advanced liver disease.</p><p><strong>Methods: </strong>This is a 45-month, stepped-wedge cluster randomized trial enrolling up to 1000 patients with advanced liver disease across 4 academic medical centers. Each site transitions from usual care to the TLC intervention on a randomized schedule at 9-month intervals. The TLC includes a post-discharge phone call within 2 business days and a hepatology advanced practice provider (APP) visit within 14 days. The primary outcome is 30-day hospital readmission. Secondary outcomes include 90-day readmission, emergency room visits, mortality, days alive out of hospital, quality of life, and patient satisfaction. Quality of life is measured with the PROMIS-29+2 Profile, and patient satisfaction is measured with the Patient Satisfaction Questionnaire-18. Follow-up occurs at 30 and 90 days post-discharge.</p><p><strong>Conclusion: </strong>This multicenter randomized trial will determine whether a structured, APP-led transitional care model can improve outcomes for patients with advanced liver disease. If successful, the TLC could serve as a scalable model for post-discharge care in hepatology.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13286549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatology e-consult responses generated by artificial intelligence demonstrate accuracy but require human oversight.","authors":"Holly K T Huang, Debra W Yen, Michelle Y Li, Gabrielle Jutras, Lisa X Deng, Charles E McCulloch, Mark J Pletcher, Jennifer C Lai, Bilal Hameed, Jin Ge","doi":"10.1097/HC9.0000000000000983","DOIUrl":"10.1097/HC9.0000000000000983","url":null,"abstract":"<p><strong>Background: </strong>Electronic consultations (e-consults) improve specialist access but burden providers. We developed LiVersa, a customized large language model (LLM) for liver diseases. We evaluated its performance in drafting hepatology e-consult responses and the equivalence between human and machine reviewers.</p><p><strong>Methods: </strong>LiVersa-generated responses for hepatology e-consults answered at the University of California San Francisco (UCSF) from January to March 2025. Using a 12-item rubric, 3 independent hepatologists and \"LLM-as-a-judge\" (OpenAI-o1) evaluated drafts against original responses. We tested equivalence between human reviewers and \"LLM-as-a-judge\" using two one-sided tests (TOST).</p><p><strong>Results: </strong>Among 61 e-consults, the most common categories were abnormal liver function tests (34%), hepatitis B (23%), and abnormal imaging (21%). LiVersa drafts demonstrated no differences from hepatologist responses in word count (284 vs. 264, p=0.47) and verbosity (24 vs. 25 words per sentence, p=0.44). Human reviewers rated 72% of drafts as reasonable starting points and 83% as providing appropriate case-specific recommendations; 10% contained misleading/incorrect information, and 3.4% posed a risk of severe harm. LiVersa performed better at avoiding misleading information and extraneous suggestions but scored lower on clinical equivalence, immediate usability, and comprehensiveness. LLM-based reviewers were more stringent than human reviewers, rating fewer drafts as clinically equivalent (27% vs. 48%) and more as potentially harmful (67% vs. 20%), with agreement on accuracy, precision, and comprehensiveness (mean difference 0.026-0.029; TOST p<0.05).</p><p><strong>Conclusions: </strong>Customized LLMs like LiVersa show promise for e-consult drafting but require human oversight. LLM-as-a-judge was more conservative than humans, supporting its role in rapid quality assurance during model updates.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13286463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-step care pathways for advanced MASLD in primary and hospital care: A multicenter study.","authors":"Stan Driessen, Koen C van Son, Tamara R Riemersma, Emily Stramigioli, Gerlinde L G Haverkamp, Maaike J Denters, Gabrielle Alblas, Eric T T L Tjwa, Nordin M J Hanssen, Sara-Joan Pinto-Sietsma, Yasaman Vali, Henrike M Hamer, Laurens A van Kleef, Diana J Leeming, Ida Lønsmann, Morten A Karsdal, Manuel Castro Cabezas, R Bart Takkenberg, Willem P Brouwer, Henk J Schers, Max Nieuwdorp, Joost P H Drenth, Maarten E Tushuizen, Adriaan G Holleboom","doi":"10.1097/HC9.0000000000000976","DOIUrl":"10.1097/HC9.0000000000000976","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) fibrosis may prevent liver-related morbidity and mortality. We investigated the effectiveness of multiple 2-step approaches for detecting at-risk advanced MASLD fibrosis, defined as a hierarchical clinical score comprising liver histology and VCTE depending on availability, in primary and hospital outpatient care.</p><p><strong>Methods: </strong>Patients at risk for MASLD were recruited from general practices and regional and tertiary internal medicine clinics, after excluding other liver diseases. Simultaneous measurement of non-invasive tests (NITs), including fibrosis-4 score (FIB4), metabolic dysfunction-associated fibrosis-5 score (MAF5), NAFLD fibrosis score (NFS), enhanced liver fibrosis (ELF) test, procollagen type III N-terminal propeptide (PRO-C3), procollagen type VI N-terminal propeptide (PRO-C6), and vibration-controlled transient elastography (VCTE), allowed testing of 2-step referral pathways. Referral patterns were compared with regular care between 2016 and 2024 using a predefined reference standard.</p><p><strong>Results: </strong>Among 595 participants, 9.4% were at-risk of advanced MASLD fibrosis. A care pathway consisting of FIB4 (≥1.30) followed by VCTE yielded the greatest improvement, increasing the correct referral rate 5.0-fold (95% CI: 2.4-10.1) compared with regular care. However, care pathways incorporating MAF5 (≥1.0) or NFS (≥-1.455) followed by VCTE demonstrated markedly higher sensitivity at comparable increases in detection (both >4.5-fold). Among other second-step NITs, PRO-C3 outperformed ELF, PRO-C6, and ADAPT, resulting in a 2.2-fold (95% CI: 1.1-4.4) increase in correct referrals when used after FIB4 (≥1.30).</p><p><strong>Conclusion: </strong>Two-step care pathways substantially improve the detection of at-risk advanced MASLD fibrosis across care settings. Pathways using FIB4, MAF5, or NFS followed by VCTE offer the best performance overall, while PRO-C3 is the most effective alternative blood-based second-step test.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High mortality at safety-net hospitals for patients with cirrhosis.","authors":"Sachin Shah, Mignote Yilma, Sabrina Omer, Amy Shui, Nicole J Kim, Kali Zhou, Michele Tana, Neil Mehta","doi":"10.1097/HC9.0000000000000964","DOIUrl":"10.1097/HC9.0000000000000964","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of NAT10 in T cells attenuates metabolic dysfunction-associated steatohepatitis in mice.","authors":"Yanying Yang, Jie Lu, Mingyue Ma, Jing Zhou, E Wang, Yan Lu, Zhe Dai, Bing Zhou, Yao Li","doi":"10.1097/HC9.0000000000000973","DOIUrl":"10.1097/HC9.0000000000000973","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of chronic liver disease, yet its pathogenesis remains incompletely understood. Immune dysregulation, particularly intrahepatic T-cell responses, is implicated in disease progression; however, the specific roles of T-cell subsets and their regulatory mechanisms are not fully defined.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) on human liver tissues from patients with varying severities of metabolic dysfunction-associated steatotic liver disease (MASLD). To establish causality, we generated T cell-specific NAT10 knockout mice. The molecular mechanism was elucidated using acetylated RNA immunoprecipitation sequencing (acRIP-seq) and mRNA stability assays.</p><p><strong>Results: </strong>scRNA-seq revealed a marked increase in NAT10 expression in intrahepatic effector CD8+ T cells from patients with severe MASLD. In mice, T cell-specific deletion of NAT10 significantly attenuated MASH progression, reducing hepatocyte injury, fibrosis, and intrahepatic CD8+ T cell accumulation. NAT10 deficiency suppressed CD8+ T cell cytotoxicity, evidenced by decreased production of IFN-γ, TNF-α, and GZMB. Mechanistically, NAT10 stabilizes Fhit mRNA through ac4C modification, enhancing its expression.</p><p><strong>Conclusions: </strong>Our study identifies NAT10 as a critical regulator of CD8+ T cell-mediated immunopathology in MASH. By stabilizing Fhit mRNA, NAT10 promotes the expression of inflammatory factors, shaping the pro-inflammatory hepatic microenvironment. Targeting NAT10 presents a promising therapeutic strategy to modulate intrahepatic immunity and arrest MASH progression.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The incidence, frequency of late liver-related complications, and transplant likelihood in pediatric acute liver failure in Californian children.","authors":"Jason T C Lee, Arianna Barbetta, Johanna Ascher Bartlett, Sarah Bangerth, Shannon Jordan, Mary Lo, Sarah Barhouma, Laura Houshmand, Linda Sher, Rohit Kohli, Kambiz Etesami, Juliet Emamaullee","doi":"10.1097/HC9.0000000000000968","DOIUrl":"10.1097/HC9.0000000000000968","url":null,"abstract":"<p><strong>Background: </strong>Early studies of pediatric acute liver failure (PALF) estimate that 60%-70% of patients survive with their native liver (SNL), 20%-25% require an emergent liver transplant (LT), and 10%-15% are mortalities. These studies were largely limited to academic centers and focused on short-term outcomes.</p><p><strong>Methods: </strong>Herein, we analyzed California Department of Healthcare Access and Information data, which is demographically representative of the US population. Between June 1990 and December 2018, 2270 children were admitted to California hospitals with PALF.</p><p><strong>Results: </strong>The overall incidence of PALF was 16.75 per 100,000 live births, with no evidence of seasonality. LT was performed in 188 (8.3%) patients and 425 (18.7%) patients died. Mortality was associated with contraindications to transplant, such as concomitant hematologic malignancy or cardiac disease. With a median follow-up of 4.5 years, nearly all deaths occurred within 4 months of presentation, with no long-term liver-related comorbidities in patients with SNL. Implementation of pediatric end-stage liver disease/MELD-based organ allocation in 2002 resulted in a more than 2-fold increase in the likelihood of LT in children <10 years (subdistribution hazard ratio: 3.35). Patients receiving care at transplant centers after this change were younger (10 vs. 12 y), more often from urban areas (98.2% vs. 94%), and more likely to receive LT for metabolic, genetic, or \"other\" causes of PALF (up to subdistribution hazard ratio 6.4 [1.84-22.26], p<0.01). While mortality was higher at transplant centers (26.5% vs. 14.6%), the time to mortality was also increased (31 vs. 7 d), likely reflecting disease complexity requiring management in a specialized children's hospital.</p><p><strong>Conclusion: </strong>In conclusion, this study supports an estimate of incidence and long-term outcomes of PALF across a large population and highlights the role of specialized pediatric transplant centers for the optimized care of PALF.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical frailty is the most important predictor of early mortality in hospitalized patients with decompensated cirrhosis.","authors":"Francesca D'Arcangelo, Laura Marta Vivian, Alberto Ferrarese, Martina Gambato, Giacomo Germani, Marco Senzolo, Francesco Paolo Russo, Patrizia Burra, Alberto Zanetto","doi":"10.1097/HC9.0000000000000972","DOIUrl":"10.1097/HC9.0000000000000972","url":null,"abstract":"<p><strong>Background: </strong>Frailty and sarcopenia are associated with mortality in cirrhosis. However, most data come from North American cohorts in the outpatient setting. We aimed to assess the impact of frailty and sarcopenia in a prospective cohort of inpatients with cirrhosis.</p><p><strong>Methods: </strong>All patients with decompensated cirrhosis admitted to our unit between October 2021 and March 2023 were prospectively screened for recruitment. Frailty was assessed using the liver frailty index, while sarcopenia was assessed via skeletal muscle index on CT scans performed during hospitalization, respectively. All patients were followed for transplant-free survival as the primary outcome.</p><p><strong>Results: </strong>We included 127 patients (median age 59 y; 68.5% male; median MELD score: 22; 70% with Child-Pugh C cirrhosis). At inclusion, 48.8% of patients were frail, and 60% were sarcopenic. Compared with robust and non-sarcopenic individuals, those with frailty and sarcopenia required ICU care more frequently during hospitalization. Moreover, frailty was associated with a longer hospital stay (15 [9-27] vs. 6.5 [4-15]; p=0.001). During a median follow-up of 96 days (IQR 37-384), 39.4% patients died. Frailty and sarcopenia were associated with a higher mortality (60% vs. 20% and 58% vs. 38%, respectively; p<0.001 and p<0.013). However, in multivariate analysis, only frailty (HR: 2.218; 95% CI: 1.314-3.743; p=0.003) was an independent predictor of reduced transplant-free survival.</p><p><strong>Conclusions: </strong>Frailty emerges as the strongest, independent predictor of early mortality in cirrhosis patients with acute decompensation. Thus, its assessment via the liver frailty index should be performed to improve risk stratification and clinical management.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL15-mediated crosstalk between LSECs and CD8⁺ tissue-resident memory T cells drives alcohol-associated hepatitis.","authors":"Weizhe Zhong, Rafael Ricci-Azevedo, Shaohua Wang, Shawna A Cooper, Jing Ma, Benjamin J Swartzwelter, Fiona Xhafi, Dejian Zhao, Hui Gao, Vijay H Shah, Suthat Liangpunsakul, Xinshou Ouyang, Wajahat Z Mehal, Sheng Cao, Zhaoli Sun, Brandon Peiffer, Yasuko Iwakiri, Robert Vassallo, Mengfei Liu","doi":"10.1097/HC9.0000000000000967","DOIUrl":"10.1097/HC9.0000000000000967","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-associated hepatitis (AH) is a severe inflammatory liver condition driven by dysregulated immune responses. CD8 T cells accumulate in the liver during AH, yet their functional role remains poorly defined.</p><p><strong>Methods: </strong>A murine NIAAA chronic-binge model with lipopolysaccharide (LPS) challenge was used. Single-cell RNA sequencing of liver and blood immune cells defined CD8 T cell subsets, followed by pathway analysis and reanalysis of human AH datasets. Spatial relationships were validated by immunohistochemistry of human AH liver tissue with CD8 TRM and liver sinusoidal endothelial cell (LSEC) co-staining. LSEC-CD8 T cell interactions were examined using in vitro co-culture, and signaling pathways were assessed by bulk RNA sequencing and phospho-protein analyses. IL15 function was evaluated by in vivo neutralization.</p><p><strong>Results: </strong>Single-cell RNA sequencing in the murine AH model revealed a distinct population of CD8 tissue-resident memory T cells (TRM) with heightened activation and proinflammatory cytokine production. Analysis of human AH liver single-cell RNA sequencing data, along with immunohistochemistry validation, supported CD8 TRM enrichment in diseased tissue. IL15 emerged as a prominent pathway linked to TRM activation, and IL15 blockade reduced TRM abundance and attenuated EtOH/ lipopolysaccharide-induced liver injury. Mechanistically, LSECs not only provided a structural niche for TRM retention but also amplified IL15 signalling. In vitro, coculture experiments demonstrated that LSECs intensified activation in pre-stimulated CD8 T cells in a stimulus-dependent manner: under IL15 stimulation, LSECs boosted effector function without inducing cell death, whereas under T-cell receptor stimulation, LSECs drove hyperactivation and activation-induced cell death. Bulk RNA-seq and phospho-protein analysis identified the PI3K-AKT pathway as a shared pathway enhanced by LSEC coculture in activated CD8 T cells. These findings define a context-dependent mechanism in which LSECs promote IL15-driven signaling through AKT pathway amplification, promoting TRM persistence and inflammatory activity in AH.</p><p><strong>Conclusions: </strong>IL15-associated signaling within the hepatic microenvironment, shaped by LSEC-CD8 T-cell interactions, promotes activation and persistence of CD8 TRM cells in AH. Targeting the IL15-LSEC-AKT axis may disrupt pathogenic TRM niches and represent a promising therapeutic strategy for severe AH.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived indole-3-propionic acid alleviates endoplasmic reticulum stress by regulating FMO2 in MASLD.","authors":"Yue Luo, Yuefeng Zhang, Qian Zhang, Xiaohan Li, Kaiwei Cai, Yaning Xu, Ruirui Zhao, Saixuan Zhang, Xinyu Bai, Haopeng Chen, Hao Li, Yanjun Hong, Qiongfeng Liao, Zhiyong Xie","doi":"10.1097/HC9.0000000000000975","DOIUrl":"10.1097/HC9.0000000000000975","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global health challenge for which there are currently no approved drugs. Indole-3-propionic acid (IPA), as one of the primary metabolites of gut microbiota, can influence the development of liver diseases through the gut-liver axis, but how it contributes to liver diseases remains unclear. The present study was conducted to explore the possible molecular mechanisms of IPA in the development of MASLD.</p><p><strong>Methods: </strong>Metabolomic analysis compared serum and fecal metabolite profiles between MASLD and normal mice. The effects of microbial metabolite IPA on MASLD were evaluated through the utilization of a mouse model and cell models. Transcriptome data analysis was used, and further validation was conducted through flow cytometry, western blotting, RNA interference, and immunoprecipitation.</p><p><strong>Results: </strong>Serum and fecal IPA levels in high-fat diet-fed mice were significantly decreased compared with those of normal chow diet-fed mice. IPA supplementation reduced hepatic lipid accumulation and alleviated insulin resistance, liver damage, and steatosis development in high-fat diet-fed mice, while gut microbiota dysbiosis was restored. Mechanistic analysis suggested that IPA promoted FMO2 expression, enhancing the interaction between FMO2 and protein kinase R-like endoplasmic reticulum kinase (PERK) and inhibiting the PERK/eIF2α/ATF4/CHOP signaling cascade, then mitigating endoplasmic reticulum (ER) stress, such as reducing hepatocyte apoptosis and reactive oxygen species levels, ultimately improving MASLD.</p><p><strong>Conclusions: </strong>IPA can promote the expression of FMO2, which binds to PERK within the ER of hepatocytes. This binding process inhibits the phosphorylation of PERK, thereby affecting PERK-mediated ER stress, and subsequently leading to a reduction in hepatocyte apoptosis and oxidation. This study puts forward the IPA/FMO2/PERK axis as a potential therapeutic target in ER stress for MASLD.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic severity is identical between normal weight and overweight adults with MASLD: Implications for the definition of lean MASLD.","authors":"Kaela Miller, Laura A Wilson, Eduardo Vilar-Gomez, Niha Samala, Liyun Yuan, Veeral Ajmera, David E Kleiner, Naga Chalasani","doi":"10.1097/HC9.0000000000000969","DOIUrl":"10.1097/HC9.0000000000000969","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"10 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}