2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T707,Steatotic liver disease (SLD) and liver fibrosis are major comorbidities in people with HIV (PWH). Guidelines recommend stepwise screening using the Fibrosis-4 (FIB-4) index followed by transient elastography (TE), yet its accuracy and the extent of FIB-4 misclassification in PWH remain uncertain. We evaluated the diagnostic performance of FIB-4 against TE, quantified missed fibrosis, and assessed whether metabolic and HIV-specific factors improve risk prediction. We conducted a multinational study of 4,917 PWH without viral hepatitis coinfection or hazardous alcohol intake undergoing TE screening across seven centers. SLD was defined by controlled attenuation parameter >275 dB/m and classified as metabolic dysfunction-associated SLD (MASLD) or metabolic dysfunction-associated alcohol-related liver disease (MetALD). Significant fibrosis (liver stiffness measurement [LSM] ≥8 kPa) was present in 12.6% of participants, advanced fibrosis (LSM ≥11 kPa) in 6.1%, and SLD in 21.7% (20.6% MASLD, 1.1% MetALD). FIB-4 showed modest accuracy for significant fibrosis (AUROC 0.69, 95% CI 0.67-0.72) and misclassified 36% of fibrosis cases as low risk (FIB-4 <1.3). Performance was poorer in MASLD than in non-MASLD (AUROC 0.60 vs 0.76; p <0.001). Participants with false-negative FIB-4 exhibited a more metabolic phenotype, including higher BMI and steatosis. Incorporating metabolic and HIV-specific factors improved discrimination and reclassification and enabled development of the FIB-HIV score, which outperformed FIB-4 (AUROC 0.78 vs 0.69; p <0.001). In PWH, liver fibrosis is common and frequently missed by FIB-4, particularly in MASLD. TE-centered screening strategies augmented by metabolic and HIV-specific indicators may improve early fibrosis detection and risk stratification.31:T9b6, Background and Aims: Steatotic liver disease (SLD) and liver fibrosis are major comorbidities in people with HIV (PWH). Guidelines recommend stepwise screening using the Fibrosis-4 (FIB-4) index followed by transient elastography (TE), yet its accuracy and the extent of FIB-4 misclassification in PWH remain uncertain. We evaluated the diagnostic performance of FIB-4 against TE, quantified missed fibrosis, and assessed whether metabolic and HIV-specific factors improve risk prediction. Approach and Results: We conducted a multinational study of 4,917 PWH without viral hepatitis coinfection or hazardous alcohol intake undergoing TE screening across seven centers. SLD was defined by controlled attenuation parameter >275 dB/m and classified as metabolic dysfunction-associated SLD (MASLD) or metabolic dysfunction-associated alcohol-related liver disease (MetALD). Significant fibrosis (liver stiffness measurement [LSM] ≥8 kPa) was present in 12.6% of participants, advanced fibrosis (LSM ≥11 kPa) in 6.1%, and SLD in 21.7% (20.6% MASLD, 1.1% MetALD). FIB-4 showed modest accuracy for significant fibrosis (AUROC 0.69, 95% CI 0.67–0.72) and misclassified 36% of fibrosis cases as low risk (FIB-4 <1.3). Performance was poorer in MASLD than in non-MASLD (AUROC 0.60 vs 0.76; p <0.001). Participants with false-negative FIB-4 exhibited a more metabolic phenotype, including higher BMI and steatosis. Incorporating metabolic and HIV-specific factors improved discrimination and reclassification and enabled development of the FIB-HIV score, which outperformed FIB-4 (AUROC 0.78 vs 0.69; p <0.001). Conclusions: In PWH, liver fibrosis is common and frequently missed by FIB-4, particularly in MASLD. TE-centered screening strategies augmented by metabolic and HIV-specific indicators may improve early fibrosis detection and risk stratification. 32:T4d4,Bile acids (BAs) flow through ducts lined by biliary epithelial cells (BECs), which preserve ductal integrity and liver homeostasis. Failure of this barrier causes BA accumulation in the liver parenchyma, and ultimately fibrosis. Here we show that BECs safeguard biliary barrier integrity and restrain BA-induced fibrogenesis through a cell-intrinsic mechanism involving farnesoid-X-receptor (FXR)-YAP signalling. Using a combination of mouse genetics, computational analysis and human samples, we show that BECs express FXR, which transcriptionally activates YAP to maintain their adhesion, thereby preventing BA efflux and subsequent FXR-dependent hepatic stellate cell activation and fibrosis in BA-dysregulated liver disease models. Genetic ablation of FXR or YAP in mouse BECs triggers β-catenin activation, mesenchymal-like conversion and BEC proliferation, promoting fibrosis-to-cirrhosis progression. Diminished FXR-YAP signalling in human BECs also parallels fibrosis severity. Consistently, obeticholic acid worsens fibrogenesis in mice with FXR-depleted BECs. Thus, BAs reprogram BECs into active guardians of tissue integrity via FXR-YAP-β-catenin signalling, preserving biliary identity and maintaining liver homeostasis.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Liver Fibrosis: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Liver Fibrosis (condition). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/condition/Liver%20Fibrosis\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Conditions\",\"item\":\"https://www.reachrx.ai/hub/tag/condition\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Liver Fibrosis\",\"item\":\"https://www.reachrx.ai/hub/tag/condition/Liver%20Fibrosis\"}]}}"}}]],["$","$L2f",null,{"title":"Liver Fibrosis: Research & Clinical Takeaways","description":"Discover peer-reviewed research on Liver Fibrosis with concise clinician summaries and next-step guidance.","papers":[{"doi":"10.1136/gutjnl-2026-339728","pmid":"42722415","title":"Ferroptosis, immune activation and MASH-related HCC","journal_title":"Gut","journal_issn":"0017-5749","published_at":"2026-09-10T00:00:00.000Z","url":"https://doi.org/10.1136/gutjnl-2026-339728","source_score":20,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-14T06:23:23.664Z","updated_at":"2026-09-14T06:23:23.664Z","tags":[{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"modality","value":"Antioxidant Therapy","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"modality","value":"Ferroptosis Inhibition","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"warning","value":"Level of evidence assigned as 7 (expert opinion/review) given the absence of primary clinical data.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"warning","value":"The DOI and publication date (September 2026) are ahead of most current literature; findings should be interpreted as emerging and hypothesis-generating.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2026-339728","tag_type":"warning","value":"This is a narrative review with no original patient data; the four-gene signature (FABP4, CAPG, QSOX1, FXN) and the DTL-PROX1 sex-dimorphism axis are proposed frameworks lacking prospective clinical validation.","value_numeric":null}],"summaries":{"what_studied":"This review examines the ferroptosis-immune axis in metabolic dysfunction-associated steatohepatitis (MASH) and its role in driving hepatocellular carcinoma (HCC), including a proposed four-gene transcriptomic signature (FABP4, CAPG, QSOX1, FXN), genetic risk polymorphisms (PNPLA3, TM6SF2, MBOAT7), and sex-based differences in iron accumulation and lipid peroxidation via the DTL-PROX1 axis.","key_result":"The authors characterise ferroptosis in MASH as a self-amplifying circuit: parenchymal ferroptotic cell death releases damage-associated molecular patterns (DAMPs) that drive myeloid and Kupffer cell activation, which in turn triggers further ferroptosis — ultimately priming oncogenic progression to HCC. A core four-gene signature maps disease transition from early metabolic stress to advanced fibrotic remodelling.","limitations":"As a narrative review, no primary patient data or clinical trial results are reported; causal relationships and the clinical validity of the four-gene signature remain unvalidated in prospective cohorts. Translational avenues described are speculative without supporting efficacy or safety data.","practice_takeaway":"Clinicians managing MASH patients — particularly those with PNPLA3, TM6SF2, or MBOAT7 risk variants — should be aware that ferroptosis and immune activation may synergistically accelerate fibrosis and HCC risk. Sex-based differences in iron metabolism and lipid peroxidation sensitivity (DTL-PROX1 axis) may warrant tailored risk stratification strategies in the future."}},{"doi":"10.1038/s42255-026-01600-1","pmid":"42698000","title":"Gut microbiota-derived imidazole propionate promotes primary sclerosing cholangitis via p38 signalling","journal_title":"Nature Metabolism","journal_issn":"2522-5812","published_at":"2026-09-04T00:00:00.000Z","url":"https://doi.org/10.1038/s42255-026-01600-1","source_score":76,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:32:03.712Z","updated_at":"2026-09-08T06:32:03.712Z","tags":[{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"condition","value":"Inflammatory Bowel Disease","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"condition","value":"Primary Sclerosing Cholangitis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"generic","value":"imidazole propionate","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"generic","value":"urocanate","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"modality","value":"Gut Microbiota Metabolite","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"modality","value":"mTORC1 Signalling","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"modality","value":"p38 MAPK Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"study_design","value":"Translational Study (Human Cohort + In Vitro + Animal Model)","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"warning","value":"Sample size for the human cohort is not explicitly stated in the provided text; tags reflect available information only.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"warning","value":"Study design is mixed (human cohort, organoid, and animal experiments); a single level of evidence is difficult to assign — level 3 reflects the best-available human cohort component.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"warning","value":"The organoid titration data (50 µM ImP chosen) is from a single donor pilot — generalizability to broader PSC populations is uncertain.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01600-1","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously: ImP is proposed as a biomarker and therapeutic target, but no clinical intervention trial has yet been conducted.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether the gut microbiota-derived metabolite imidazole propionate (ImP) drives disease progression in primary sclerosing cholangitis (PSC), using human cohorts (including post-liver-transplant patients), patient-derived cholangiocyte organoids, and chronic ImP administration in wild-type and p38γ-δ knockout mice.","key_result":"Individuals with PSC had higher circulating ImP levels than those with related conditions, and elevated ImP predicted reduced survival. In PSC-derived cholangiocyte organoids, 50 µM ImP significantly increased pro-inflammatory (TNF-α, ICAM1, CXCL2, IL-6, IL-1β, IFN-γ) and pro-fibrotic (FAP, MMP-9, fibronectin) factors versus vehicle. Chronic ImP administration in mice induced liver inflammation and portal fibrosis (collagen content significantly higher in portal tracts, p=0.043) via a p38-dependent, mTORC1-upstream mechanism.","limitations":"- Mouse model uses exogenous ImP administration rather than microbiota-derived ImP, which may not fully replicate human disease dynamics.\n- Organoid experiments used only three PSC donor models (PDO-PSC-A, B, C), limiting generalizability.\n- Recurrent PSC diagnosis criteria varied between imaging and histology, introducing potential misclassification.","practice_takeaway":"Clinicians managing PSC should be aware that gut-derived ImP may be a measurable prognostic biomarker and a potential therapeutic target — strategies aimed at reducing ImP production (e.g., gut microbiota modulation) or blocking p38/mTORC1 signalling warrant further clinical investigation."}},{"doi":"10.1038/s42255-026-01590-0","pmid":"42698001","title":"UBE2N deficiency contributes to MASH development via p62-regulated mitophagy and PANoptosis","journal_title":"Nature Metabolism","journal_issn":"2522-5812","published_at":"2026-09-04T00:00:00.000Z","url":"https://doi.org/10.1038/s42255-026-01590-0","source_score":6,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-09T06:21:09.200Z","updated_at":"2026-09-09T06:21:09.200Z","tags":[{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"generic","value":"UBE2N","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"modality","value":"Ubiquitin-Proteasome System Modulator","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"sample_size","value":"n=22","value_numeric":22},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"study_design","value":"Preclinical Animal Study with Human Tissue Validation","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"warning","value":"Sample size tag reflects the human TMA cohort (12 MASH cases + 10 controls) described in the supplementary datasheet; the main mouse study sample sizes are not extractable from the provided content.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"warning","value":"Study design label is approximate; the paper combines mouse genetic models with human tissue arrays and mechanistic cell work, which does not map cleanly to a single standard design category.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"warning","value":"The full text provided is largely metadata and a tissue microarray datasheet; detailed quantitative results, figures, and statistical data from the main manuscript were not available for extraction — summaries are based primarily on the abstract.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01590-0","tag_type":"warning","value":"The tissue microarray donor cohort is predominantly female and Caucasian, which may limit demographic generalizability of the human validation data.","value_numeric":null}],"summaries":{"what_studied":"This study examined the role of UBE2N (a K63-linked ubiquitin-conjugating enzyme) in metabolic dysfunction-associated steatohepatitis (MASH), using hepatocyte-specific knockout and overexpression mouse models on a western diet, alongside human liver tissue analysis.","key_result":"Hepatocyte-specific *Ube2n* deficiency worsened western diet-induced MASH and fibrosis by impairing PARKIN-mediated K63-linked ubiquitination of p62 at lysine 420, blocking mitophagic clearance, causing cytoplasmic p62 accumulation, NRF2 hyperactivation, and PANoptosis. UBE2N overexpression reversed these pathologies. Additional *Sqstm1* (p62) deletion mitigated *Ube2n*-knockout-induced disease, confirming p62 accumulation as a key driver.","limitations":"The full text available is largely supplementary/metadata; key quantitative outcome data (e.g., fibrosis scores, cell death rates) are not extractable from the provided content. The human tissue microarray includes a small, predominantly female Caucasian cohort (n=12 MASH cases), limiting generalizability. Findings are based on mouse western diet models, which may not fully recapitulate human MASH progression.","practice_takeaway":"UBE2N and p62 represent emerging mechanistic targets in MASH; while not yet clinically actionable, these findings position p62 modulation as a potential therapeutic strategy for MASH and liver fibrosis worthy of further translational investigation."}},{"doi":"10.1097/hep.0000000000001856","pmid":"42691332","title":"Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH","journal_title":"Hepatology","journal_issn":"0270-9139","published_at":"2026-09-02T00:00:00.000Z","url":"https://doi.org/10.1097/hep.0000000000001856","source_score":8,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:32:07.969Z","updated_at":"2026-09-08T06:32:07.969Z","tags":[{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"generic","value":"pegozafermin","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"modality","value":"Fibroblast Growth Factor 21 Analog","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"sample_size","value":"n=160","value_numeric":160},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"study_design","value":"Prospective Cohort Study (Nested within Randomized Controlled Trial)","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"warning","value":"MASH and NASH are used interchangeably in the literature; this paper uses the updated 'MASH' nomenclature throughout.","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"warning","value":"The study design is described as 'prospective' but participants were enrolled within an RCT (pegozafermin phase 2b trial); the diagnostic accuracy analysis is observational, not randomized. Level of evidence reflects the prospective diagnostic cohort design.","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001856","tag_type":"warning","value":"The validation cohort (n=48) is small, making the AUC of 0.62 wide-CI and potentially underpowered to confirm or refute the primary finding.","value_numeric":null}],"summaries":{"what_studied":"This prospective study evaluated whether a ≥30% relative decline in VCTE-derived liver stiffness measurement (LSM) accurately identifies histologic fibrosis regression (without worsening MASH) in 160 adults with biopsy-proven MASH and stage 2–3 fibrosis, drawn from a phase 2b RCT of pegozafermin, with a separate validation cohort of n=48.","key_result":"A ≥30% relative decline in LSM showed only modest diagnostic accuracy for fibrosis regression: AUC 0.68 (95% CI 0.58–0.77) in the primary cohort and AUC 0.62 (95% CI 0.48–0.76) in the validation cohort. However, it was independently associated with fibrosis regression (adjusted OR 4.23, 95% CI 1.79–10.38, p=0.001).","limitations":"- Validation cohort was small (n=48) and geographically limited (U.S. and Singapore), reducing generalizability.\n- Participants came from a single RCT of one agent (pegozafermin), so findings may not apply to other therapies or MASH populations.\n- The study was restricted to stage 2–3 fibrosis; results may not extend to stage 1 or stage 4.","practice_takeaway":"A ≥30% drop in VCTE liver stiffness is independently linked to fibrosis regression in MASH but has only modest accuracy (AUC ~0.68), so it should not be used alone as a surrogate endpoint for treatment response. Clinicians and trialists should await more precise non-invasive biomarkers before relying on this threshold."}},{"doi":"10.14309/ajg.0000000000004191","pmid":"42678758","title":"Do Patients on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Require Longer Fasting Prior to Vibration Controlled Transient Elastography?","journal_title":"American Journal of Gastroenterology","journal_issn":"0002-9270","published_at":"2026-09-01T00:00:00.000Z","url":"https://doi.org/10.14309/ajg.0000000000004191","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:32:12.850Z","updated_at":"2026-09-08T06:32:12.850Z","tags":[{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"condition","value":"Cirrhosis","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"modality","value":"Transient Elastography","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"sample_size","value":"n=23","value_numeric":23},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"study_design","value":"Prospective Observational Study","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"warning","value":"No specific GLP-1 RA agents, doses, or drug durations are reported in the abstract, limiting applicability to individual agents.","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"warning","value":"Sex of participants is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"warning","value":"Study design is not explicitly labeled in the abstract; classified as prospective observational based on context (serial measurements after standardized meal). Confirm in full text.","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004191","tag_type":"warning","value":"The proportion of patients who required 4 hours to return to baseline is not quantified — clinicians should interpret the 'subset' caveat cautiously.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated whether the standard 3-hour fasting recommendation before vibration-controlled transient elastography (VCTE) remains adequate in patients on GLP-1 receptor agonists (GLP-1 RAs), which delay gastric emptying and alter postprandial hemodynamics. 23 participants (including 12 with cirrhosis) underwent serial liver stiffness measurements (LSM) after a standardized meal.","key_result":"LSM peaked at 20.6% above baseline at 30–60 minutes post-meal, then fell to <10% above baseline by 3 hours. Most patients returned to baseline by 3–4 hours, supporting the adequacy of a 3-hour fast, though some required up to 4 hours.","limitations":"Very small sample size (n=23) limits generalizability. The study does not stratify results by GLP-1 RA agent, dose, or duration of use. The subset requiring 4 hours is not precisely quantified.","practice_takeaway":"A standard 3-hour fast before VCTE appears adequate for most patients on GLP-1 RAs, but clinicians should be aware that a subset may need 4 hours. Consider extending the fast to 4 hours when results seem unexpectedly elevated."}},{"doi":"10.1016/s2468-1253(26)00154-8","pmid":"42648297","title":"ALG-055009 in non-cirrhotic adults with metabolic dysfunction-associated steatohepatitis (HERALD): a randomised, double-blind, placebo-controlled, phase 2a trial","journal_title":"The Lancet Gastroenterology & Hepatology","journal_issn":"2468-1253","published_at":"2026-08-26T00:00:00.000Z","url":"https://doi.org/10.1016/s2468-1253(26)00154-8","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-02T06:22:24.926Z","updated_at":"2026-09-02T06:22:24.926Z","tags":[{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"generic","value":"ALG-055009","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"sample_size","value":"n=102","value_numeric":102},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"warning","value":"ALG-055009 has no approved brand name or RxNorm canonical generic entry as of the knowledge cutoff; it is an investigational compound only.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"warning","value":"MASH diagnosis was 'presumed' rather than biopsy-confirmed, which is a material caveat for interpreting baseline fibrosis stage data.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"warning","value":"No histologic endpoints (e.g., NAS score, fibrosis regression) were assessed; liver fat by MRI-PDFF is a surrogate only.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00154-8","tag_type":"warning","value":"The 0.9 mg cohort was restricted to participants weighing >85 kg, limiting cross-dose comparisons.","value_numeric":null}],"summaries":{"what_studied":"This phase 2a RCT (HERALD, NCT06342947) evaluated four oral doses of ALG-055009 (0.3, 0.5, 0.7, or 0.9 mg once daily) vs. placebo over 12 weeks in 102 non-cirrhotic adults (aged 18–75, BMI ≥25 kg/m²) with presumed MASH and F1–F3 liver fibrosis, measuring hepatic fat reduction by MRI-PDFF as the primary endpoint.","key_result":"The 0.7 mg and 0.9 mg doses produced statistically significant, placebo-adjusted reductions in liver fat at 12 weeks: −33.2% (95% CI −48.1 to −18.3; p<0.0001) and −31.6% (95% CI −47.4 to −15.8; p=0.0001), respectively. Treatment-emergent adverse events were similar to placebo (45–65% on drug vs. 73% placebo), mostly mild/moderate GI events, with no deaths and no clinically meaningful changes in thyroid function.","limitations":"- Short 12-week duration with only MRI-PDFF as the endpoint; no histologic outcomes assessed.\n- Diagnosis of MASH was presumed (not biopsy-confirmed at enrollment), limiting certainty about baseline disease severity.\n- Small per-group sample sizes (n=18–22) reduce precision and generalizability.","practice_takeaway":"ALG-055009 at 0.7–0.9 mg daily cut liver fat by roughly one-third vs. placebo over 12 weeks with a safety profile comparable to placebo — a notable early signal for this THR-β agonist. Longer trials with histologic endpoints are needed before clinical adoption."}},{"doi":"10.1038/s41575-026-01235-3","pmid":"42567912","title":"The dynamic spectrum of steatotic liver disease: the global perspective","journal_title":"Nature Reviews Gastroenterology & Hepatology","journal_issn":"1759-5045","published_at":"2026-08-07T00:00:00.000Z","url":"https://doi.org/10.1038/s41575-026-01235-3","source_score":13,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-13T13:22:59.753Z","updated_at":"2026-08-13T13:22:59.753Z","tags":[{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"condition","value":"Alcohol-Related Liver Disease","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"condition","value":"Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"generic","value":"phosphatidylethanol","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"modality","value":"Non-Invasive Fibrosis Assessment","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"warning","value":"No specific patient numbers, effect sizes, or trial data are present in the abstract; quantitative tags such as sample size could not be assigned.","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"warning","value":"The impact_flag 'practice_changing' is assigned based on the review's explicit advocacy for a paradigm shift in SLD classification and management, but this is a narrative review without primary trial data.","value_numeric":null},{"paper_doi":"10.1038/s41575-026-01235-3","tag_type":"warning","value":"The PDF metadata and full text content do not match the abstract — the uploaded PDF appears to be a USDA food security survey module unrelated to the stated paper on steatotic liver disease. Structured output is based solely on the provided abstract, as no supporting full text on SLD was available.","value_numeric":null}],"summaries":{"what_studied":"This review examines the full spectrum of steatotic liver disease (SLD) — including metabolic dysfunction-associated SLD, combined metabolic and alcohol-related liver disease, and alcohol-related liver disease — with a focus on how cardiometabolic risk factors and alcohol interact dynamically over time.","key_result":"Cardiometabolic risk factors (obesity, type 2 diabetes, hypertension, dyslipidaemia) are highly prevalent across all SLD subtypes and interact synergistically with alcohol to accelerate fibrosis progression; static diagnostic thresholds frequently misclassify patients due to fluctuating risks and under-reporting of alcohol intake.","limitations":"Most emerging pharmacotherapies for metabolic dysfunction-associated steatohepatitis exclude patients with concurrent alcohol use, limiting generalizability to real-world SLD populations; the review does not report original trial data or specific outcome numbers.","practice_takeaway":"Clinicians should use objective alcohol biomarkers (e.g., phosphatidylethanol) alongside systematic cardiometabolic risk evaluation and non-invasive fibrosis assessment, rather than relying on static diagnostic categories. Repeated reassessment over time is key, as patients can shift across the SLD spectrum."}},{"doi":"10.1097/hc9.0000000000001013","pmid":"42520169","title":"The risk of cardiovascular events in metabolic dysfunction–associated steatotic liver disease according to fibrosis stage and diabetes status: A cohort study","journal_title":"Hepatology Communications","journal_issn":"2471-254X","published_at":"2026-08-01T00:00:00.000Z","url":"https://doi.org/10.1097/hc9.0000000000001013","source_score":13,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-01T13:21:58.299Z","updated_at":"2026-08-01T13:21:58.299Z","tags":[{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"condition","value":"Prediabetes","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"condition","value":"Type 2 Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"generic","value":"fibrosis-4 index","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"generic","value":"vibration-controlled transient elastography","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"modality","value":"Noninvasive Fibrosis Assessment","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"sample_size","value":"n=6519","value_numeric":6519},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"warning","value":"Approximately half the baseline MASLD cohort (3,298/6,519) lacked follow-up records and were excluded from survival analysis; the included cohort was older and had more comorbidities, which may overestimate event rates.","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"warning","value":"The AGA pathway could not generate hazard ratios for the diabetes subgroup due to structural pathway constraints (no subjects in the very low-risk tier; no events in the highest-risk tier), limiting direct comparisons between pathways.","value_numeric":null},{"paper_doi":"10.1097/hc9.0000000000001013","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the novel finding that fibrosis staging adds ASCVD risk stratification specifically in prediabetes and younger MASLD patients, but the single-center Asian cohort and lack of external validation temper the strength of this claim.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study examined whether liver fibrosis severity—classified by the KASL/EASL and AGA sequential noninvasive pathways (FIB-4 followed by VCTE)—was associated with incident clinical ASCVD in 6,519 adults with MASLD, stratified by glycemic status (normoglycemia, prediabetes, diabetes), at a single Korean health screening center (2012–2020).","key_result":"In the prediabetes subgroup (n=2,369), the highest fibrosis tier carried a significantly higher ASCVD risk (adjusted sHR 2.62, 95% CI 1.14–6.01, p=0.024), with 5-year cumulative incidence rising from 9.5% (low tier) to 22.0% (highest tier). In patients with diabetes, 5-year cumulative ASCVD incidence was uniformly high across all fibrosis tiers (15.2%–18.5%) with no significant gradient by fibrosis severity. The association was more pronounced in younger individuals (<65 years).","limitations":"- Single-center Korean health screening cohort limits generalizability to other ethnicities and settings.\n- Retrospective design with ~49% of MASLD subjects lacking follow-up records; the survival cohort was slightly older with more comorbidities, introducing potential selection bias.\n- Fibrosis classified by NITs (FIB-4 + VCTE) without histological confirmation, and no time-dependent AUC analyses or head-to-head comparison with established ASCVD prediction models were performed.","practice_takeaway":"In MASLD patients with prediabetes—especially younger adults—higher noninvasive fibrosis tier (FIB-4 ≥1.3 + liver stiffness ≥8 kPa) signals meaningfully elevated ASCVD risk and should prompt closer cardiometabolic review. In patients with established diabetes, ASCVD risk is already high regardless of fibrosis tier, so standard cardiovascular risk tools remain the primary guide."}},{"doi":"10.1093/ejhf/xuag243","pmid":"42533713","title":"Evaluation and management of heart failure patients with liver disease: European Journal of Heart Failure international expert position paper","journal_title":"European Journal of Heart Failure","journal_issn":"1388-9842","published_at":"2026-07-31T00:00:00.000Z","url":"https://doi.org/10.1093/ejhf/xuag243","source_score":45,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-14T13:24:58.024Z","updated_at":"2026-08-14T13:24:58.024Z","tags":[{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"condition","value":"Chronic Liver Disease","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"condition","value":"Heart Failure","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"condition","value":"Hepatic Congestion","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"study_design","value":"Expert Position Paper / Narrative Review","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"warning","value":"No primary trial data or patient-level outcomes are reported; findings reflect expert consensus and narrative synthesis only.","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"warning","value":"Sample size tag omitted as this is a review with no enrolled study population.","value_numeric":null},{"paper_doi":"10.1093/ejhf/xuag243","tag_type":"warning","value":"Study design is ambiguous between a position paper and a clinical review — tagged accordingly, but formal guideline grading is absent.","value_numeric":null}],"summaries":{"what_studied":"This international expert position paper evaluates the epidemiology, diagnosis, and management of patients with concurrent heart failure (HF) and chronic liver disease (CLD), addressing shared pathophysiology, diagnostic pitfalls, drug metabolism challenges, and therapeutic strategies.","key_result":"The paper identifies a bidirectional, worsening overlap between HF and CLD driven by shared risk factors, underscores the under-representation of CLD patients in landmark HF trials, and highlights key diagnostic challenges — particularly distinguishing primary liver disease from HF-related hepatic congestion and estimating fibrosis severity accurately.","limitations":"As a position paper and expert review, it does not present primary trial data or quantitative outcomes. Conclusions are limited by the lack of dedicated clinical trials in HF patients with CLD, making evidence-based recommendations difficult to grade.","practice_takeaway":"Clinicians should interpret liver marker abnormalities cautiously in HF patients, as congestion, altered hemodynamics, and drug metabolism can all confound results. A structured cardiovascular-hepatic evaluation is needed to differentiate HF-related liver congestion from primary liver disease before treatment decisions."}},{"doi":"10.1111/jgh.70614","pmid":"42521276","title":"Comparing the Effect of Changes in Alcohol Intake on Liver Fibrosis Risk Scores Among Patients With Two Distinct Types of Steatotic Liver Disease","journal_title":"Journal of Gastroenterology and Hepatology","journal_issn":"0815-9319","published_at":"2026-07-28T00:00:00.000Z","url":"https://doi.org/10.1111/jgh.70614","source_score":9,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-01T13:22:02.409Z","updated_at":"2026-08-01T13:22:02.409Z","tags":[{"paper_doi":"10.1111/jgh.70614","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"condition","value":"Metabolic Dysfunction and Alcohol-Associated Liver Disease","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"modality","value":"Lifestyle Modification","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"sample_size","value":"n=2842","value_numeric":2842},{"paper_doi":"10.1111/jgh.70614","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"warning","value":"Alcohol intake was self-reported, which may underestimate true consumption levels, particularly in the MetALD group.","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"warning","value":"Fibrosis endpoints were based on non-invasive risk scores, not histology — exact scoring tools used are not specified in the abstract.","value_numeric":null},{"paper_doi":"10.1111/jgh.70614","tag_type":"warning","value":"The sex-specific findings (especially for women with MASLD) may be underpowered given the overall sample distribution is not broken down by sex.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study examined how changes in alcohol consumption over time affected liver fibrosis risk scores (FRS) in 2,198 patients with MASLD and 644 with MetALD, each completing at least three health check-ups ≥1 year apart.","key_result":"FRS were higher in MetALD than MASLD patients. Women with MASLD who increased alcohol intake had worsening FRS; men with MASLD showed no association. In MetALD — particularly men drinking 280–419.9 g/week — reducing alcohol intake lowered the risk of further FRS worsening compared to maintaining the same consumption level.","limitations":"Retrospective observational design limits causal inference; fibrosis was assessed via non-invasive risk scores rather than liver biopsy; alcohol intake relied on self-report, subject to underreporting bias.","practice_takeaway":"Counsel all MetALD patients to reduce alcohol intake, as doing so is associated with lower fibrosis progression risk — especially in men with higher baseline consumption. For women with MASLD, even modest increases in alcohol use may worsen fibrosis risk and warrant proactive guidance."}},{"doi":"10.1016/s2468-1253(26)00123-8","pmid":"42456707","title":"Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial","journal_title":"The Lancet Gastroenterology & Hepatology","journal_issn":"2468-1253","published_at":"2026-07-16T00:00:00.000Z","url":"https://doi.org/10.1016/s2468-1253(26)00123-8","source_score":109,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-20T13:35:53.404Z","updated_at":"2026-07-20T13:35:53.404Z","tags":[{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"brand","value":"Wegovy","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"condition","value":"Compensated Cirrhosis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"generic","value":"cagrilintide","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"generic","value":"zalfermin","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"modality","value":"Amylin Analogue","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"modality","value":"FGF21 Analogue","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"sample_size","value":"n=698","value_numeric":698},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"warning","value":"Cagrilintide + semaglutide arm was exploratory only — no formal hypothesis testing was planned for this arm.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"warning","value":"One death (heart failure in the zalfermin 30 mg group) was assessed as possibly related to study drug; small numbers limit safety conclusions.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"warning","value":"The semaglutide monotherapy result is nominally significant only (p=0.024 without correction for multiple comparisons); it should not be interpreted as a confirmed treatment effect.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00123-8","tag_type":"warning","value":"Zalfermin is an investigational FGF21 analogue not yet approved; the brand tag 'Wegovy' is assigned to semaglutide 2.4 mg based on the approved dose, though the trial context is investigational.","value_numeric":null}],"summaries":{"what_studied":"This phase 2 RCT evaluated once-weekly subcutaneous zalfermin (7.5 mg, 15 mg, or 30 mg) co-administered with semaglutide 2.4 mg vs. semaglutide alone, zalfermin alone, cagrilintide + semaglutide, or placebo over 52 weeks in 698 adults with biopsy-confirmed MASH and fibrosis stages F2–F4c (including compensated cirrhosis).","key_result":"The primary endpoint — ≥1-stage fibrosis improvement with no MASH worsening at 52 weeks — was not met for zalfermin 30 mg + semaglutide vs. placebo (24% vs. 16%; EDP 7.98, 95% CI −3.82 to 19.79; p=0.19). Semaglutide 2.4 mg alone showed a nominally significant benefit vs. placebo (30% vs. 16%; EDP 14.05, 95% CI 1.88–26.23; p=0.024).","limitations":"- The trial was not powered to show significance for each arm individually, and multiple comparisons limit the strength of the semaglutide finding (nominal p-value only).\n- The 52-week biopsy endpoint may be too short to capture full antifibrotic effects, especially in F4c cirrhosis.\n- Sponsor (Novo Nordisk) funding introduces potential conflicts of interest.","practice_takeaway":"Zalfermin combined with semaglutide did not outperform placebo for fibrosis improvement in MASH — adding zalfermin to semaglutide does not appear beneficial at this stage. Semaglutide 2.4 mg alone showed a nominally significant antifibrotic signal, including in compensated cirrhosis (F4c), and may warrant further evaluation as a disease-modifying therapy in this population."}},{"doi":"10.1038/s42255-026-01543-7","pmid":"42448794","title":"A data-driven framework reconstructs the molecular continuum of human MASLD progression","journal_title":"Nature Metabolism","journal_issn":"2522-5812","published_at":"2026-07-14T00:00:00.000Z","url":"https://doi.org/10.1038/s42255-026-01543-7","source_score":23,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-20T13:35:56.213Z","updated_at":"2026-07-20T13:35:56.213Z","tags":[{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"condition","value":"Liver Cirrhosis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"modality","value":"Plasma Proteomics","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"modality","value":"Transcriptomic Biomarker Panel","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"study_design","value":"Cross-Sectional Study with Computational Trajectory Analysis","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"warning","value":"Sample size (total N) is not explicitly stated in the abstract or provided full text excerpt; the tag could not be populated.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"warning","value":"Study design involves computational pseudotime-like trajectory inference from cross-sectional data, which differs from standard observational study designs — causal directionality cannot be confirmed.","value_numeric":null},{"paper_doi":"10.1038/s42255-026-01543-7","tag_type":"warning","value":"The 'practice_changing' impact flag is assigned cautiously: the biomarker panel outperforms existing scores in the study cohorts, but prospective clinical validation is still needed.","value_numeric":null}],"summaries":{"key_result":"A 57-gene plasma-accessible biomarker panel accurately predicted advanced fibrosis and continuously positioned patients along the MASLD disease trajectory across independent cohorts, outperforming established non-invasive clinical scores.","what_studied":"This study built a data-driven framework to reconstruct MASLD progression as a continuous molecular trajectory using cross-sectional liver transcriptomic profiles from two cohorts (UCAM and VCU/Sanyal datasets), then integrated paired liver-plasma proteomics to identify non-invasive biomarkers for disease staging.","limitations":"The study is cross-sectional rather than longitudinal, so the reconstructed trajectory is inferred rather than directly observed. The biomarker panel has not yet been validated in prospective clinical settings. Analysis relies on batch-corrected transcriptomic data from two cohorts, which may limit generalizability.","practice_takeaway":"A 57-gene plasma protein panel may offer more precise, non-invasive staging of MASLD — including advanced fibrosis — than current scores like FIB-4 or APRI. This framework also provides a roadmap for identifying stage-specific therapeutic targets in MASLD."}},{"doi":"10.14309/ajg.0000000000004114","pmid":"42424626","title":"Dietary Guidelines 2025-2030 For Americans Are Concerning For Liver Health","journal_title":"American Journal of Gastroenterology","journal_issn":"0002-9270","published_at":"2026-07-09T00:00:00.000Z","url":"https://doi.org/10.14309/ajg.0000000000004114","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-18T13:39:57.977Z","updated_at":"2026-07-18T13:39:57.977Z","tags":[{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"condition","value":"Cirrhosis","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"condition","value":"Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"modality","value":"Dietary Intervention","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"sample_size","value":"n=10944","value_numeric":10944},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"warning","value":"The alcohol 'adherence score' was derived from DGA-2020 thresholds (prior guidelines), not a validated clinical tool—interpretation should be made with caution.","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the study's direct critique of active federal dietary policy (DGA-2025), but causal conclusions are limited by the cross-sectional design.","value_numeric":null},{"paper_doi":"10.14309/ajg.0000000000004114","tag_type":"warning","value":"VCTE was used for liver assessment; results may not perfectly align with biopsy-based staging.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study of 10,944 U.S. adults (NHANES 2017–2023) examined how individual dietary components—scored via HEI-2020 and energy-adjusted z-scores aligned to DGA-2025 food groups—relate to steatotic liver disease (SLD), fibrosis, and cirrhosis, using vibration-controlled transient elastography (VCTE) as the outcome measure.","key_result":"Higher intake of fruits, vegetables, greens and beans, whole grains, and seafood/plant protein was linked to lower odds of SLD and fibrosis; higher intake of red/processed meats, sodium, total protein, saturated fat, and added sugars was linked to greater prevalence. In stepwise models, greens and beans, seafood/plant protein, saturated fat, and alcohol use were retained as independent predictors. Notably, DGA-2025-emphasized components (total protein, red meat) were associated with greater fibrosis risk, while several protective components were omitted from the updated guidelines.","limitations":"- Cross-sectional design limits causal inference.\n- Dietary assessment relied on a single 24-hour recall, which may not reflect habitual intake.\n- VCTE-based fibrosis staging is a surrogate; histologic confirmation was not available.","practice_takeaway":"Counsel patients at risk for fatty liver disease to prioritize plant-based proteins (legumes, seafood) and limit red/processed meat, saturated fat, and added sugars—patterns not fully reflected in the DGA-2025. The complete omission of alcohol guidance in DGA-2025 is a notable gap, as alcohol adherence was one of the strongest protective factors for liver outcomes in this analysis."}},{"doi":"10.1007/s00125-026-06774-7","pmid":"42322377","title":"Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis","journal_title":"Diabetologia","journal_issn":"0012-186X","published_at":"2026-06-20T00:00:00.000Z","url":"https://doi.org/10.1007/s00125-026-06774-7","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:38.654Z","updated_at":"2026-06-27T13:27:38.654Z","tags":[{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"condition","value":"Insulin Resistance","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"generic","value":"lanifibranor","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"generic","value":"liraglutide","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"generic","value":"pioglitazone","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"generic","value":"saroglitazar","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"modality","value":"FGF19 Analogue","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"modality","value":"FGF21 Analogue","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"modality","value":"PPAR Agonist","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"modality","value":"Thiazolidinedione","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"modality","value":"Thyroid Hormone Receptor-Beta Agonist","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"warning","value":"No sample size is applicable as this is a review article; sample_size tag omitted.","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"warning","value":"Sex-hormone findings (e.g., HRT and MASLD outcomes) are largely from retrospective or preclinical data; ongoing RCTs (COMHO-MASLD, NCT04833140) have not yet reported results.","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"warning","value":"The 'practice_changing' impact flag reflects FDA/EMA approval of resmetirom and semaglutide for MASH, referenced within the review, not a novel trial finding of this paper itself.","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06774-7","tag_type":"warning","value":"This is a narrative review — evidence grading reflects author synthesis, not systematic meta-analysis; individual study quality varies widely.","value_numeric":null}],"summaries":{"what_studied":"This narrative review synthesises current evidence on the metabolic and hormonal drivers of MASLD and MASH progression — covering insulin/glucagon imbalance, adipose tissue dysfunction, de novo lipogenesis, mitochondrial failure, sex hormones, the gut–liver–adipose axis, and fibrogenic signalling — with a focus on how systemic dysfunction translates into hepatic inflammation and fibrosis.","key_result":"Insulin–glucagon imbalance is identified as the central integrative driver of MASLD progression: chronic hyperinsulinaemia promotes de novo lipogenesis via Akt/mTORC1–SREBP1c and directly activates hepatic stellate cells, while impaired glucagon action limits lipid oxidation and amino acid disposal. Fibrosis stage (not inflammation) is the main predictor of clinical outcomes, and gluconeogenic flux correlates with fibrosis stage rather than steatosis degree. Approved therapies now include resmetirom (THR-β agonist) and semaglutide (GLP-1RA) for non-cirrhotic MASH with F2–F3 fibrosis.","limitations":"- Narrative (not systematic) review; evidence synthesis is selective and not exhaustive.\n- Much gut-dysbiosis and sex-hormone data (including HRT for MASLD) is associative; prospective/interventional validation is lacking.\n- Causality between adipose tissue insulin resistance (Adipo-IR) and liver fibrosis in humans remains difficult to establish directly.","practice_takeaway":"Clinicians managing MASLD/MASH should assess adipose tissue insulin resistance (Adipo-IR index) alongside standard liver metrics, as it independently predicts fibrosis severity and tracks response to thiazolidinediones. Resmetirom and semaglutide are now approved for non-cirrhotic MASH (F2–F3); dual/pan-incretin and PPAR agonist strategies are in late-stage trials and may offer broader metabolic benefits."}},{"doi":"10.1161/circresaha.126.327269","pmid":"42241512","title":"Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease","journal_title":"Circulation Research","journal_issn":"0009-7330","published_at":"2026-06-04T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13240654/","source_score":14,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:24:26.142Z","updated_at":"2026-06-10T14:24:26.142Z","tags":[{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Dyslipidemia","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Insulin Resistance","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"modality","value":"Lipoprotein Metabolism","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"modality","value":"VLDL Secretion","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"warning","value":"MASLD terminology reflects recent nomenclature updates (formerly NAFLD/NASH); findings may not map directly to older literature using prior terminology.","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the novel subtype-based CVD risk stratification concept, but clinical validation in prospective studies is still needed.","value_numeric":null},{"paper_doi":"10.1161/circresaha.126.327269","tag_type":"warning","value":"This is a narrative review — no original patient data, effect sizes, or absolute risk numbers are reported; the 'key result' reflects the authors' conceptual framework rather than a quantified outcome.","value_numeric":null}],"summaries":{"what_studied":"This review examines how hepatic lipid and lipoprotein metabolism pathways differ across MASLD subtypes — one driven by systemic metabolic dysfunction (obesity, insulin resistance) and one driven by genetic/familial factors impairing VLDL secretion — and how these subtypes relate to cardiometabolic and CVD risk.","key_result":"Two dominant MASLD subtypes were identified: (1) a metabolic/obesity-driven subtype associated with **increased** CVD risk, and (2) a genetic/familial subtype characterized by impaired VLDL secretion associated with **reduced** CVD risk — suggesting cardiovascular risk is not uniform across MASLD.","limitations":"As a narrative review, no original data are presented and findings reflect the authors' synthesis of existing evidence rather than a systematic or meta-analytic approach. Causal directionality between MASLD subtypes and CVD outcomes is not formally established.","practice_takeaway":"Not all MASLD carries the same cardiovascular risk — clinicians should consider whether a patient's liver disease is driven by metabolic dysfunction (higher CVD risk) vs. genetic factors impairing VLDL secretion (lower CVD risk) when stratifying and managing cardiometabolic risk. Phenotyping MASLD subtypes may guide more tailored therapeutic strategies."}},{"doi":"10.1016/s2468-1253(26)00091-9","pmid":"42229495","title":"Liver stiffness dynamics in European populations (LiverScreen): a longitudinal, multicentre, prospective, population-based cohort study","journal_title":"The Lancet Gastroenterology & Hepatology","journal_issn":"2468-1253","published_at":"2026-06-02T00:00:00.000Z","url":"https://doi.org/10.1016/s2468-1253(26)00091-9","source_score":24,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-11T13:42:47.390Z","updated_at":"2026-06-11T13:42:47.390Z","tags":[{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"condition","value":"Alcohol-Related Liver Disease","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"modality","value":"Vibration-Controlled Transient Elastography","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"sample_size","value":"n=4536","value_numeric":4536},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"warning","value":"Median age of 62 years and IQR 56–68 means the cohort skews older; applicability to younger adults is uncertain.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously — the finding that low-risk general populations have minimal LSM progression challenges current broad screening paradigms, but formal guideline updates have not yet been reported.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00091-9","tag_type":"warning","value":"The study spans three distinct European cohorts (Barcelona, Odense, Rotterdam) with different recruitment strategies (primary care, alcohol-risk, general population), which may introduce heterogeneity in baseline risk profiles. Results should be interpreted with this variation in mind.","value_numeric":null}],"summaries":{"what_studied":"This prospective, population-based cohort study tracked liver stiffness measurement (LSM) dynamics via vibration-controlled transient elastography in 4,536 European adults across three cohorts (Barcelona, Odense, Rotterdam) over a median follow-up of 4.3 years, identifying risk factors for clinically significant LSM changes (≥30% change crossing the 8.0 kPa threshold).","key_result":"Among participants with a baseline LSM ≥8.0 kPa (n=251), 43.8% had a clinically significant LSM **decrease** at follow-up. Among those with baseline LSM <8.0 kPa (n=4,285), only 2.6% had a clinically significant **increase** — suggesting low progression rates in the general population but notable spontaneous regression in those already above threshold.","limitations":"- Three European cohorts may limit generalizability to non-European or lower-income populations.\n- 588 participants had no follow-up LSM due to logistical constraints, and 1,286 declined follow-up, introducing possible selection bias.\n- LSM alone (without biopsy confirmation) was used to define clinically significant change, which may misclassify some cases.","practice_takeaway":"Population-wide repeated LSM screening has a low yield; target rescreening to high-risk individuals (obesity, harmful alcohol use, type 2 diabetes, elevated ALT). For patients who screen positive (LSM ≥8.0 kPa), short-term confirmatory testing is reasonable given the high rate of spontaneous LSM decrease."}},{"doi":"10.1111/apt.70750","pmid":"42218732","title":"The Prevalence and Risk Factors for at‐Risk\n MASH\n and Advanced Liver Fibrosis in People With Metabolic Risk Factors in Primary Care","journal_title":"Alimentary Pharmacology & Therapeutics","journal_issn":"0269-2813","published_at":"2026-05-31T00:00:00.000Z","url":"https://doi.org/10.1111/apt.70750","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-09T13:50:28.464Z","updated_at":"2026-06-09T13:50:28.464Z","tags":[{"paper_doi":"10.1111/apt.70750","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"modality","value":"Non-Invasive Liver Fibrosis Assessment","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"sample_size","value":"n=110938","value_numeric":110938},{"paper_doi":"10.1111/apt.70750","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"warning","value":"FNI data was only available for ~15% of the full cohort (16,586 of 110,938), which may introduce selection bias in at-risk MASH prevalence estimates.","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"warning","value":"Study population is from Victoria, Australia; findings may not generalize to other healthcare systems or ethnic populations.","value_numeric":null},{"paper_doi":"10.1111/apt.70750","tag_type":"warning","value":"The 'impact_flag: practice_changing' tag reflects the large-scale primary care evidence supporting routine risk stratification, though the study design is cross-sectional and observational.","value_numeric":null}],"summaries":{"what_studied":"Cross-sectional study of 110,938 adults with metabolic dysfunction across 84 general practices in Victoria, Australia, assessing the prevalence of at-risk MASH (via Fibrotic NASH Index) and advanced liver fibrosis (via FIB-4) over a 12-month period in primary care.","key_result":"Among those with FNI data (n=16,586), 24.3% had at-risk MASH; among those with FIB-4 data (n=64,948), 16.3% needed further liver assessment and 4.3% had advanced fibrosis. Male sex, type 2 diabetes, hypertension, and socioeconomic disadvantage were independently associated with worse outcomes.","limitations":"Non-invasive surrogate indices (FNI, FIB-4) used in place of liver biopsy; FNI data available for only ~15% of the cohort, limiting generalizability; cross-sectional design prevents causal inference.","practice_takeaway":"Nearly 1 in 4 primary care patients with metabolic dysfunction may have at-risk MASH — prioritize FIB-4 screening in those with type 2 diabetes or hypertension. Socioeconomic disadvantage is an independent risk factor, so consider broader public health and equity-focused approaches alongside clinical risk stratification."}},{"doi":"10.1016/j.jhep.2026.04.029","pmid":"42191458","title":"EASL position paper on preclinical models of steatotic liver disease","journal_title":"Journal of Hepatology","journal_issn":"0168-8278","published_at":"2026-05-27T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhep.2026.04.029","source_score":4,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-04T13:23:40.328Z","updated_at":"2026-06-04T13:23:40.328Z","tags":[{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Alcohol-Associated Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Liver Cirrhosis","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Liver Fibrosis","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"condition","value":"Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"study_design","value":"Position Paper / Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"warning","value":"No original patient or animal data are presented; this is a consensus/expert position paper, so level of evidence is advisory rather than empirical.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"warning","value":"The DOI year (2026) is consistent with the stated publication date; the paper is newly published as of the current date.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.04.029","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the field-wide standardisation implications for preclinical researchers, not direct clinical practice change.","value_numeric":null}],"summaries":{"what_studied":"This EASL position paper critically reviews and classifies preclinical experimental models (in vivo, in vitro, ex vivo) used to study steatotic liver disease (SLD), including MASLD/MASH, MetALD, and ALD, proposing criteria for appropriate model selection across distinct SLD subtypes.","key_result":"The paper proposes a framework for categorising and standardising SLD preclinical models based on criteria spanning systemic and hepatic metabolism, cardiometabolic comorbidities, histopathology, immunopathology, and molecular features relevant to disease stage and aetiology.","limitations":"As a position paper, recommendations are consensus- and expert opinion-based rather than derived from new empirical data; the breadth of models reviewed may limit the depth of guidance for any single model.","practice_takeaway":"Researchers selecting preclinical SLD models should align model choice with the specific disease subtype (MASLD, MetALD, ALD), disease stage, and translational question using the standardised criteria proposed here. Consistent use of updated nomenclature (e.g., MASLD/MASH replacing NAFLD/NASH) is recommended across experimental SLD research."}},{"doi":"10.1097/hep.0000000000001773","pmid":"42065895","title":"FIB-4 fails to identify significant liver fibrosis in people with HIV: A large multinational screening study","journal_title":"Hepatology","journal_issn":"0270-9139","published_at":"2026-05-01T00:00:00.000Z","url":"https://doi.org/10.1097/hep.0000000000001773","source_score":22,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-08","doi":"10.1097/hep.0000000000001773","days":"7","issn":"0270-9139","rank":"5","field":"Clinical Medicine","score":"22","category":"Gastroenterology & Hepatology","categories":["Gastroenterology & Hepatology"],"_categories":["Gastroenterology & Hepatology"]},"pubmed":{"doi":"10.1097/HEP.0000000000001773","title":"FIB-4 fails to identify significant liver fibrosis in people with HIV: A large multinational screening study.","journal":"Hepatology (Baltimore, Md.)","methods":"","results":"","abstract":"$30","keywords":["FIB-HIV","MASLD","lean phenotype","metabolic risk factors","misclassification","transient elastography"],"pubmed_id":"42065895","conclusions":"","publication_date":"2026-05-01T00:00:00"},"crossref":{"DOI":"10.1097/hep.0000000000001773","URL":"https://doi.org/10.1097/hep.0000000000001773","ISSN":["0270-9139","1527-3350"],"link":[{"URL":"https://journals.lww.com/10.1097/HEP.0000000000001773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["FIB-4 fails to identify significant liver fibrosis in people with HIV: A large multinational screening study"],"author":[{"given":"Felice","family":"Cinque","sequence":"first","affiliation":[{"name":"Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada"},{"name":"Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy"}]},{"given":"Sahar","family":"Saeed","sequence":"additional","affiliation":[{"name":"Public Health Sciences, Queen’s University, Kingston, ON, Canada"}]},{"given":"Francesca","family":"Farina","sequence":"additional","affiliation":[{"name":"Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada"},{"name":"San Raffaele Hospital, Milan, Italy"}]},{"given":"Dana","family":"Kablawi","sequence":"additional","affiliation":[{"name":"Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada"}]},{"given":"Jihoon","family":"Lim","sequence":"additional","affiliation":[{"name":"Center for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Canada"}]},{"given":"Antonio","family":"Cascio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences and Mother and Child Care “Giuseppe D’Alessandro”, University of Palermo, Palermo, Italy"}]},{"given":"Claudia","family":"Gioè","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences and Mother and Child Care “Giuseppe D’Alessandro”, University of Palermo, Palermo, Italy"}]},{"given":"Emmanuel","family":"Tsochatzis","sequence":"additional","affiliation":[{"name":"UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK"}]},{"given":"Rosa","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy"},{"name":"SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy"}]},{"given":"Ahmed","family":"Cordie","sequence":"additional","affiliation":[{"name":"Endemic Medicine Department, Cairo University Hospitals, Cairo, Egypt"}]},{"given":"Rahma","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Endemic Medicine Department, Cairo University Hospitals, Cairo, Egypt"}]},{"given":"Ahmed M.","family":"Kamel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt"}]},{"given":"Gamal","family":"Esmat","sequence":"additional","affiliation":[{"name":"Endemic Medicine Department, Cairo University Hospitals, Cairo, Egypt"},{"name":"Research Center, Badr University in Cairo, Badr City, Egypt"}]},{"given":"Alessandra","family":"Bandera","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy"},{"name":"Infectious Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy"}]},{"given":"Jovana","family":"Milic","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy"}]},{"given":"Dominik","family":"Benke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, Bonn, Germany"}]},{"given":"Fauzi","family":"Elamouri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, Bonn, Germany"}]},{"given":"Jürgen K.","family":"Rockstroh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Venusberg Campus 1, University Hospital Bonn, Bonn, Germany"}]},{"given":"Giovanni","family":"Guaraldi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy"}]},{"given":"Giada","family":"Sebastiani","sequence":"additional","affiliation":[{"name":"Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada"},{"name":"Center for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Canada"},{"name":"Division of Gastroenterology and Hepatology, Royal Victoria Hospital, McGill University Health Centre, Montreal, Canada"}]}],"issued":{"date-parts":[[2026,5,1]]},"member":"276","prefix":"10.1097","source":"Crossref","volume":null,"created":{"date-time":"2026-05-01T16:00:14Z","timestamp":1777651214000,"date-parts":[[2026,5,1]]},"indexed":{"date-time":"2026-05-07T10:15:07Z","timestamp":1778148907187,"date-parts":[[2026,5,7]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://journals.lww.com/10.1097/HEP.0000000000001773"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","value":"2026-02-04"},{"name":"accepted","group":{"name":"publication_history","label":"Publication 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age_group and sex tags reflect reasonable assumptions for an HIV clinic population.","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001773","tag_type":"warning","value":"The FIB-HIV score is newly derived in this study; external validation data are not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1097/hep.0000000000001773","tag_type":"warning","value":"The full text retrieved appears to contain an unrelated document (a 2020 GI Society joint statement on racism), not the actual study body. Summary and tags are based solely on the abstract, which provides sufficient detail for most fields but precludes extraction of subgroup data, adjustment variables, or methodological specifics from the full text.","value_numeric":null}],"summaries":{"what_studied":"Diagnostic accuracy of FIB-4 index vs. transient elastography (TE) for significant liver fibrosis in 4,917 people with HIV (PWH) without viral hepatitis coinfection or hazardous alcohol use, across seven multinational centers; also assessed whether metabolic and HIV-specific factors could improve risk prediction.","key_result":"FIB-4 showed only modest accuracy for significant fibrosis (AUROC 0.69) and missed 36% of cases (false-negative rate at FIB-4 <1.3 cutoff); performance was worse in MASLD vs. non-MASLD (AUROC 0.60 vs. 0.76, p<0.001). A new FIB-HIV score incorporating metabolic and HIV-specific factors outperformed FIB-4 (AUROC 0.78 vs. 0.69, p<0.001). Significant fibrosis (LSM ≥8 kPa) was present in 12.6% and SLD in 21.7% of participants.","limitations":"- Observational, cross-sectional design limits causal inference and assessment of clinical outcomes.\n- TE used as reference standard rather than liver biopsy, which may affect fibrosis classification accuracy.\n- The FIB-HIV score was derived and not externally validated in an independent cohort.","practice_takeaway":"FIB-4 alone should not be relied upon to rule out significant fibrosis in PWH, especially those with metabolic risk factors or MASLD — TE-based screening is more appropriate in this population. Clinicians should consider metabolic and HIV-specific factors when stratifying fibrosis risk in PWH."}},{"doi":"10.1038/s42255-026-01521-z","pmid":"42049952","title":"FXR–YAP signalling maintains biliary epithelial cell identity and preserves liver homeostasis","journal_title":"Nature Metabolism","journal_issn":"2522-5812","published_at":"2026-04-29T00:00:00.000Z","url":"https://doi.org/10.1038/s42255-026-01521-z","source_score":54,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-04-30","doi":"10.1038/s42255-026-01521-z","days":"14","issn":"2522-5812","rank":"5","field":"Clinical Medicine","score":"54","category":"Endocrinology & Metabolism","categories":["Endocrinology & Metabolism"],"_categories":["Endocrinology & Metabolism"]},"pubmed":{"doi":"10.1038/s42255-026-01521-z","title":"FXR-YAP signalling maintains biliary epithelial cell identity and preserves liver homeostasis.","journal":"Nature 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