Neurogastroenterol Motil
· 2026 Jun · PMID 42324735
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BACKGROUND: Evidence suggests psychological factors including personality traits can have impact on the development and course of irritable bowel syndrome (IBS) and associated health-related quality of life (HrQoL), with...BACKGROUND: Evidence suggests psychological factors including personality traits can have impact on the development and course of irritable bowel syndrome (IBS) and associated health-related quality of life (HrQoL), with large individual heterogeneity. Main aim of this study was to examine between-persons associations and within-sample concurrent associations of the personality traits neuroticism, extraversion, conscientiousness, openness and agreeableness with gastrointestinal (GI) symptoms, psychological factors and HrQoL in IBS-patients. METHODS: Cross-sectional data from an observational IBS-study (n = 194, mean age 51.36 years, 74.4% female) was used. Patients completed the Big Five Inventory (BFI)-44 questionnaire regarding personality traits, and questionnaires on symptom severity (GSRS-IBS), general anxiety (HADS-A, GAD-7), GI-specific anxiety (VSI), and HrQoL (36-SF). A multivariable regression model and a network correlation analysis were performed. KEY RESULTS: Neuroticism showed the most relevant between-persons associations, confirmed by within-sample concurrent associations: associated with increased GI-specific anxiety (B 7.234, p = 0.040), general anxiety (B 0.954, p = 0.040), and decreased mental HrQoL (B-3.576, p = 0.007). Extraversion showed an opposing pattern including increased mental HrQoL (B = 4.266, p = 0.001), with strong association to neuroticism. While no significant between-person associations emerged between abdominal pain and personality traits, significantly associated to higher general anxiety (B = 6.304, p < 0.001) and GI-specific anxiety (B = 0.034, p < 0.001) were shown. CONCLUSION: This study reinforces the association between personality traits and IBS, highlighting the integral connection to not only other psychological factors but also GI-symptoms. These findings support a multifactorial, personalized approach to IBS, advocating for the integration of personality assessment-particularly neuroticism and extraversion-into the biopsychosocial model.
Wei H, Heo S, Yang Y
… +38 more, Li M, Fu F, Xia T, Lee SS, Choi ES, Sartoris R, Grégory J, Kwok CY, Wang L, Pan J, Zhang Y, Cannella R, Wu Z, Wu Y, Jia X, Wu Y, Wang Y, Duan T, Yang T, Sheng L, Yang C, Feng ST, Kuang M, Sun HC, Wang Y, Wang M, Ju S, Chernyak V, Nault JC, Chan SL, Lee JM, Tan CH, Li W, Bashir MR, Chen F, Ronot M, Song B, Jiang H
BACKGROUND & AIMS: Very early recurrence (within one year after resection) of hepatocellular carcinoma (HCC) indicates aggressive tumor biology and poor prognosis, yet noninvasive prediction tools remain scarce. This stu...BACKGROUND & AIMS: Very early recurrence (within one year after resection) of hepatocellular carcinoma (HCC) indicates aggressive tumor biology and poor prognosis, yet noninvasive prediction tools remain scarce. This study aimed to develop and validate MRI-based models for very early recurrence prediction and explore their biological underpinnings. METHODS: This international, multicenter cohort study retrospectively included 1811 consecutive patients who underwent curative-intent resection for single BCLC 0/A HCC and preoperative contrast-enhanced MRI or CT across 14 tertiary-care hospitals in China, South Korea, Singapore, France and the USA, and 40 eligible patients from TCGA-LIHC dataset. To predict 1-year recurrence-free survival (RFS), MRI for Very Early Recurrence Prediction (MERP) models were developed using preoperative variables alone (MERP-pre) or combining pre- and postoperative variables (MERP-post) in the derivation cohort (n=628), externally validated in Eastern (n=775) and Western (n=178) test cohorts, and extrapolated to a CT test cohort (n=230). Biological correlates were investigated using whole-exome and RNA sequencing. RESULTS: MERP-pre incorporated alpha-fetoprotein, tumor size, portal venous phase peritumoral hypoenhancement, and blood products in mass, while MERP-post replaced tumor size with microvascular invasion (MVI). Both models outperformed major staging systems and IMbrave050 criteria across all test cohorts (C-indexes, 0.685-0.790 vs. 0.524-0.682; P values, <0.001 to 0.046) and improved risk reclassification (net reclassification improvement [NRI], 0.004-0.372). MERP models consistently stratified patients into high- and low-risk groups with distinct 1-year RFS rates (all P<0.001). MERP-pre further improved MVI-based reclassification (NRI, 0.323) and survival risk stratification. MERP-pre low-risk tumors demonstrated non-proliferative class features, increased lipid catabolism, and an immunoactive microenvironment. CONCLUSIONS: MERP models may serve as robust, generalizable, and biologically correlated tools for predicting very early HCC recurrence, holding promise for refining risk-stratified management. IMPACT AND IMPLICATIONS: Very early recurrence (VER) of hepatocellular carcinoma (HCC) within one year after resection denotes aggressive tumor biology and poor prognosis, yet reliable tools for predicting VER remain scarce. In this large, international, multicenter cohort of patients with single Barcelona Clinic Liver Cancer stage 0/A HCC undergoing curative-intent resection, we developed and externally validated two MRI-based models (MERP-pre and MERP-post) that integrate routinely available clinicopathological and imaging variables. The MERP models consistently outperformed currently adopted prognostic systems and effectively stratified patients into high- and low-risk groups with distinct 1-year recurrence-free survival across diverse cohorts. These advances underscore the potential of MERP models to complement existing systems for optimizing risk-stratified management of HCC.
BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is an increasingly significant contributor to primary liver cancer in the Asia-Pacific region, with substantial regional variation. To quantify t...BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) is an increasingly significant contributor to primary liver cancer in the Asia-Pacific region, with substantial regional variation. To quantify the burden and temporal trends of MASH-related liver cancer across countries and subregions from 1990 to 2023. METHODS: Using the Global Burden of Disease (GBD) 2023 dataset, we analysed age-standardized prevalence, deaths, and disability-adjusted life years (DALYs) for MASH-related liver cancer, assessing temporal trends, regional variation and associations with the Socio-demographic Index (SDI). Decomposition analysis estimated the contributions of ageing, population growth and epidemiological changes. RESULTS: In 2023, the high-income Asia-Pacific region had the highest age-standardized prevalence of MASH-related liver cancer (1.19 per 100 000), followed by Oceania (0.98 per 100 000) and Australasia (0.88 per 100 000), with Central Asia the lowest (0.56 per 100 000). Across the Asia-Pacific region, prevalence, mortality and DALYs generally increased with SDI, though patterns varied by subregion. The high-income Asia-Pacific region showed a distinct 'increase-peak-decline' pattern in both mortality and DALYs, whereas low- and middle-income regions (i.e., South Asia, South-east Asia and Central Asia) showed steady increases in prevalence. Pacific island nations experienced disproportionately higher DALYs despite their smaller populations. Decomposition analyses showed that ageing and population growth accounted for the largest proportions of the observed changes in East Asia (44.8% and 41.4%, respectively) and South Asia (41.1% and 30.1%, respectively), whereas epidemiological change was the largest contributor in Australasia (58.4%). CONCLUSIONS: MASH-related liver cancer is rising across the Asia-Pacific region, with substantial regional variation, underscoring the need for region-specific public health strategies.
Banz M, Hagel S, Freiburger S
… +10 more, Huhn F, Krause M, Glöckner S, Löffler B, Nurjadi D, Muthukumarasamy U, Jundzill M, Kaasch AJ, Pletz MW, Brandt C
Microbial cell-free DNA (mcfDNA) enables rapid and sensitive pathogen detection via direct plasma-sequencing. Here, we present a fast, cost-effective mcfDNA multiplex workflow to complement or improve the sensitivity of...Microbial cell-free DNA (mcfDNA) enables rapid and sensitive pathogen detection via direct plasma-sequencing. Here, we present a fast, cost-effective mcfDNA multiplex workflow to complement or improve the sensitivity of microbiological diagnostics for systemic and focal infections which can be challenged by prior antibiotic treatment or non-culturable pathogens. In an explorative study of 18 patients, mcfDNA sequencing matched the clinical diagnosis in 16 cases (89%), was detected up to 16 days after starting targeted antibiotic therapy and identified Staphylococcus aureus in two cases of culture-negative endocarditis. By providing an open-access protocol, we aim to promote broader accessibility and globally available application.
BACKGROUND: Gastrointestinal symptom-specific anxiety (GSA) is increasingly recognized as an important construct in the disease experience of inflammatory bowel diseases (IBD). However, it remains unclear to what extent...BACKGROUND: Gastrointestinal symptom-specific anxiety (GSA) is increasingly recognized as an important construct in the disease experience of inflammatory bowel diseases (IBD). However, it remains unclear to what extent GSA overlaps with general anxiety in the IBD population, and whether it is associated with disability beyond general anxiety and other clinical and demographic variables. AIMS: First, we examined how many patients with elevated GSA do or do not experience general anxiety, and vice versa. Second, we assessed the unique contribution of GSA to variance in IBD-related disability, keeping general anxiety, disease activity, and other variables constant. METHODS: In a cross-sectional survey study, over 1000 IBD patients completed questionnaires on general anxiety (the anxiety subscale of the Hospital Anxiety and Depression Scale [HADS]), GSA (the Visceral Sensitivity Index [VSI]), IBD-related disability (the IBD Disk), and self-reported clinical disease activity (Patient-Reported Outcomes [PRO] and Manitoba IBD Index [MIBDI]) alongside a set of general demographic and clinical questions. RESULTS: GSA and general anxiety frequently co-occurred, but 38.0% of patients reported GSA without general anxiety. Additionally, GSA was significantly associated with IBD-related disability (P < .001) even when general anxiety, disease activity, and other variables were controlled for. Although general anxiety showed the strongest association with disability (β = .27), the association for GSA (β = 0.22) was stronger than for clinical disease activity (β = .18) and other demographic and clinical variables. CONCLUSION: Overall, this highlights the clinical significance of GSA beyond general anxiety and disease activity in IBD.
Yoder L, Tapper EB, Kalman R
… +7 more, Rinella M, Bendin N, Verma M, Pike F, Chalasani N, Nalumasu N, Orman ES
Hepatol Commun
· 2026 Jul · PMID 42319136
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BACKGROUND: 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 effi...BACKGROUND: 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. METHODS: 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. CONCLUSION: 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.
Parikh ND, Liu CC, DeMaio M
… +9 more, Yeh AH, Stackpole ML, Li S, Agopian VG, Li W, Zhou XJ, Ni X, Lok AS, Han SB
Hepatol Commun
· 2026 Jul · PMID 42319131
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BACKGROUND: Semi-annual abdominal ultrasound plus alpha-fetoprotein (AFP) is recommended for HCC surveillance but has limited performance, particularly in patients with metabolic dysfunction-associated steatotic liver di...BACKGROUND: Semi-annual abdominal ultrasound plus alpha-fetoprotein (AFP) is recommended for HCC surveillance but has limited performance, particularly in patients with metabolic dysfunction-associated steatotic liver disease. We aimed to validate a blood-based test combining cell-free DNA methylation profiling with AFP to improve HCC detection in at-risk individuals. METHODS: Between September 1, 2023, and April 30, 2025, 135 patients with HCC and 167 at risk for HCC were prospectively recruited at 2o medical centers; archived samples (46 HCC and 32 at-risk) were also included. A cell-free DNA methylation assay was performed to generate methylation scores, and AFP testing was conducted as part of standard of care. A pretrained model integrated methylation scores and AFP levels for HCC detection. RESULTS: The combination of methylation and AFP tests achieved an AUC of 0.94 (95% CI, 0.92-0.96) for detecting HCC in at-risk individuals, significantly outperforming both methylation alone (AUC: 0.92, 95% CI, 0.89-0.95; p=0.001) and AFP alone (AUC: 0.83, 95% CI, 0.79-0.87; p<0.0001). In patients with early-stage HCC (within Milan Criteria), the combined test achieved an AUC of 0.90 (95% CI, 0.86-0.94), outperforming methylation alone (AUC: 0.88, 95% CI, 0.83-0.92; p=0.002) and AFP alone (AUC: 0.81, 95% CI, 0.76-0.86; p<0.0001). At 92.0% specificity, sensitivity for early-stage HCC was 73% (95% CI, 64%-80%) with the combined test, compared with 62% (95% CI, 52%-71%; p=0.025) for methylation alone and 52% (95% CI, 43%-62%; p<0.0001) for AFP alone. Sensitivity improvements were consistent across major demographic and etiologic subgroups. CONCLUSIONS: The combination of cell-free DNA methylation with AFP shows promising performance for early-stage HCC detection in this case-control validation study and warrants further validation.
An ICD-10 code specific for hepatic encephalopathy (HE), K76.82, was introduced in October of 2022. We aimed to assess changes in HE documentation following the introduction of this code. Using the National Inpatient Sam...An ICD-10 code specific for hepatic encephalopathy (HE), K76.82, was introduced in October of 2022. We aimed to assess changes in HE documentation following the introduction of this code. Using the National Inpatient Sample, we compared utilization of ICD-10 codes historically used to identify HE before and after K76.82. From 2016 to 2021, 20.0% of cirrhosis hospitalizations included a non-specific HE code, decreasing to 4.7% in 2023. K76.82 was used in 20.3% of hospitalizations in 2023. The introduction of K76.82 has dramatically changed the documentation of HE, and future studies assessing HE trends and outcomes need to account for these changes.
Xiao P, Zai Q, Ma N
… +20 more, Zhang J, Hao Y, Zhou Y, Zhang F, Liu T, Sun H, Zhang J, Liu X, Ge S, Ling S, Chen Y, Li Y, Yang L, Ren G, Rodrigues RM, Xiang X, Li M, Niu J, Gao Y, He Y
BACKGROUND & AIMS: Acetaminophen (APAP) overdose is the leading cause of acute liver failure in Western countries. However, the inflammatory mechanisms underlying APAP-induced liver injury (AILI) remain obscure. Interleu...BACKGROUND & AIMS: Acetaminophen (APAP) overdose is the leading cause of acute liver failure in Western countries. However, the inflammatory mechanisms underlying APAP-induced liver injury (AILI) remain obscure. Interleukin (IL)-19 exerts its function via binding to the IL-20 receptor complex (IL-20R1/IL-20R2). This study aims to investigate the role of IL-19 in AILI. METHODS: Il19 deficient mice and myeloid cell-specific Il20r2 knockout mice were generated and subjected to AILI. Single-cell RNA sequencing (ScRNA-seq) was performed to analyze liver macrophage subsets. RESULTS: Il19 deficient mice displayed heightened susceptibility to AILI, which was accompanied by a distinct transcriptional profile with a pronounced increase in proinflammatory macrophage infiltration. Treatment with recombinant IL-19 markedly suppressed proinflammatory macrophage infiltration, mitigating AILI. ScRNA-Seq analysis revealed that Il20r2 deficiency in myeloid cells exacerbated AILI due to increased infiltration of S100A8/A9 proinflammatory macrophages. Mechanistically, IL-19 downregulated CCAAT/ enhancer binding protein β (C/EBPβ) protein expression in macrophages by promoting its post-translational SUMOylation, which diminished the transcriptional control of proinflammatory genes that regulated S100A8/A9 expression, ultimately ameliorating AILI. CONCLUSIONS: IL-19 is a key determinant of limiting proinflammatory macrophage infiltration, thus ameliorating AILI in the early stage. Our study suggests that IL-19 may represent a potential target for treating AILI. IMPACT AND IMPLICATIONS: IL-19, a member of the IL-10 family, exerts its function via binding to the IL-20 receptor complex (IL-20R1/IL-20R2); however, its exact functions and in-depth mechanisms in liver diseases remain poorly understood. In this study, we concluded that IL-19 protects against APAP-induced liver injury by limiting S100A8/A9 proinflammatory macrophage infiltration as evidenced that Il19 knockout and myeloid cell-specific Il20r2 deficient mice were more susceptible to APAP hepatotoxicity, exhibiting a distinct transcriptional landscape characterized by an obviously elevated S100A8/A9 proinflammatory macrophage infiltration. IL-19 may be a novel therapeutic anti-inflammatory cytokine via SUMOylating of C/EBPβ, playing a key role in limiting proinflammatory cell infiltration during acute liver injury.
Goossens N, Garay OU, Wolf C
… +3 more, Ambüehl LE, Kugler V, Girardin FR
Swiss Med Wkly
· 2026 May · PMID 42312979
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BACKGROUND: European and Swiss guidelines recommend hepatocellular carcinoma surveillance of high-risk patients every 6 months using ultrasound (US), with/without α-fetoprotein (AFP). Other surveillance strategies are av...BACKGROUND: European and Swiss guidelines recommend hepatocellular carcinoma surveillance of high-risk patients every 6 months using ultrasound (US), with/without α-fetoprotein (AFP). Other surveillance strategies are available, but evidence of their comparative cost-effectiveness is lacking. This study evaluated the cost-effectiveness of current hepatocellular carcinoma surveillance strategies in Switzerland, including the novel GAAD (gender [biological sex], age, α-fetoprotein, protein induced by vitamin K absence or antagonist-II [PIVKA-II]) serum-based algorithm in high-risk patients. METHODS: A micro-simulated Markov model estimated the cost-effectiveness of hepatocellular carcinoma surveillance strategies (no surveillance, US, US+AFP, GAAD) performed at 6-monthly intervals in a simulated cohort of 100,000 patients with compensated liver cirrhosis over a lifetime horizon. Performance parameters were sourced from published meta-analyses and multicentre study data. Epidemiological parameters were estimated based on literature identified during a previous systematic literature review. Similarly, utility parameters were sourced from published literature. Costs were sourced from TARMED, the Analysis List, the Swiss Federal Statistical Office, publicly available data and published literature. Primary outcomes were life years lived, quality-adjusted life years, and costs per patient and per cohort. The cost-effectiveness of each strategy was analysed through incremental cost-effectiveness ratios at a cost-effectiveness threshold of Swiss Franc (CHF) 100,000/quality-adjusted life year. RESULTS: Overall, the total costs and quality-adjusted life years per patient, respectively, were CHF 43,493.61 and 5.893 for no surveillance; CHF 48,702.79 and 6.018 for US; CHF 49,980.60 and 6.042 for US+AFP; and CHF 49,983.10 and 6.048 for GAAD. Compared with US+AFP and US alone, GAAD was cost-effective, with higher quality-adjusted life years and the highest rate of early-stage hepatocellular carcinoma detection (56%). Compared with no surveillance, incremental cost-effectiveness ratios for US, US+AFP and GAAD were considered to be cost-effective, ranging from CHF 41,509.01 to CHF 43,321.81. CONCLUSIONS: The current model indicates that hepatocellular carcinoma surveillance with any of these strategies was cost-effective in Switzerland. GAAD was nearly cost-neutral versus US+AFP, although these findings were dependent on the performance of GAAD and operator-dependent US combined with AFP. Compared with US alone, GAAD was the most cost-effective strategy. Further investigations are required to confirm these findings and to optimise hepatocellular carcinoma surveillance.
Jairath V, Magro F, Protic M
… +13 more, De Hertogh G, Harpaz N, Hisamatsu T, D'Haens G, Pai R, Yu G, Morris N, Luo WT, Hon E, Escobar R, Biedermann L, Reinisch W, VIVID Study Group
J Crohns Colitis
· 2026 Jun · PMID 42309525
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BACKGROUND AND AIMS: Evaluation of microscopic inflammation is an emerging therapeutic target of Crohn's disease. The completed VIVID-1 trial evaluated histologic and combined histologic-endoscopic outcomes for mirikizum...BACKGROUND AND AIMS: Evaluation of microscopic inflammation is an emerging therapeutic target of Crohn's disease. The completed VIVID-1 trial evaluated histologic and combined histologic-endoscopic outcomes for mirikizumab relative to placebo and ustekinumab in moderately-to-severely active Crohn's disease. METHODS: Two specimens from each of five intestinal segments (one ileal, four colonic) were obtained from the edge of ulcers, or the most inflamed mucosa at screening, and weeks (W)12 and 52. Histologic response was defined as the absence of epithelial neutrophils and epithelial damage, erosions and ulceration or ≥50% decrease in either the active Robarts Histopathology Index or the active Global Histologic Disease Activity Score, and was prespecified. Histologic remission was defined as absence of mucosal neutrophils, no epithelial damage, and no erosions and ulcers and was a prespecified endpoint. Post-hoc analyses included subgroup analyses, the proportions of patients achieving combined histologic-endoscopic outcomes, the agreement between histologic outcomes and endoscopic or clinical outcomes, segmental analyses, the assessment of cut-off points for fecal calprotectin, and the association between W12 histologic outcomes and selected W52 outcomes. RESULTS: At W12, mirikizumab was superior to placebo for histologic response (P < .0001) and histologic remission (P = .001), with similar rates to ustekinumab (P = .58 and P = .44, respectively). At W52, mirikizumab-treated patients showed greater histologic response (P = .008) compared to ustekinumab, especially in patients who previously failed biologic therapies (P = .006). Combined histologic-endoscopic response at W52 was numerically higher for mirikizumab (P = .06) and reached statistical significance among biologic-failed patients (P = .02); however, combined remission rates were comparable across treatment arms. CONCLUSIONS: Mirikizumab was superior to placebo in achievement of all histology-based endpoints. Mirikizumab showed higher rates compared to ustekinumab for achievement of histologic response at W52. Early histologic response among endoscopic non-responders was associated with 1-year endoscopic outcomes. ClinicalTrials.gov, NCT03926130.
BACKGROUND & AIMS: Glycosylated proteins and lipids regulate multiple cellular processes and play key roles in organ damage and regeneration. Recently, glycosylated non-coding small RNAs (glycoRNA) have been identified,...BACKGROUND & AIMS: Glycosylated proteins and lipids regulate multiple cellular processes and play key roles in organ damage and regeneration. Recently, glycosylated non-coding small RNAs (glycoRNA) have been identified, however, their expression in the liver and their involvement in hepatic pathology has not yet been reported. METHODS: We detected the presence of glycoRNAs by northern blot and an imaging approach called sialic acid aptamer and RNA in situ hybridization-mediated proximity ligation assay that enables direct visualization of glycoRNAs. Restoration of key mediators of glycoRNA biosynthesis was achieved in vivo, via adeno-associated viral vectors (AAV). RESULTS: Here, we show that glycoRNAs are synthesized in human liver tissue, primary hepatocytes and hepatic tumor cells. In tissues from patients with key features of metabolic dysfunction-associated steatotic liver diseases (MASLD), the most prevalent liver disease worldwide, expression of most glycoRNAs was reduced. Mechanistically, we found that reduced expression of SID1 transmembrane family member 1 (SIDT1) and DTW domain containing 2 (DTWD2), two key mediators of glycoRNA biosynthesis, contribute to loss of glycoRNAs in MASLD. Inhibition of SIDT1 and DTWD2 increased fatty acid load in primary human hepatocytes and enhanced inflammation signals upon co-culture with macrophages. Importantly, AAV-mediated in vivo restoration of SIDT1 and DTWD2 attenuated metabolic dysfunction-associated steatohepatitis (MASH) in mice. Furthermore, sequencing of enriched glycoRNA samples identified eight glycoRNAs, which were downregulated in steatotic human liver and hepatocytes. CONCLUSIONS: Collectively, our study demonstrates the presence of glycoRNAs in human hepatocytes and human liver tissues and their dysregulated expression in experimental steatosis models and in MASLD patients. IMPACT AND IMPLICATIONS: Recent estimates suggest that up to 24% of the world's population is affected by metabolic dysfunction-associated steatotic liver diseases (MASLD). Our study reports for the first time that glycosylated RNAs (glycoRNA), a recently discovered class of RNA, are present in the liver and their expression is dysregulated in fatty liver injury. Importantly, in vivo restoration of glycoRNA biogenesis, attenuated fatty liver injury in preclinical models of MASLD. Furthermore, our results suggest that glycoRNA expression is dysregulated in human livers with MASLD, indicating their potential as novel biomarkers of liver injury.