3b:I[281230,["/_next/static/immutable/chunks/0l5c-zsrs2aic.js","/_next/static/immutable/chunks/3_n0rk2989-8h.js","/_next/static/immutable/chunks/3ofw495lt1gr1.js","/_next/static/immutable/chunks/3tofdpg99uc12.js","/_next/static/immutable/chunks/2rzojj6zgb9d9.js","/_next/static/immutable/chunks/42jxjvozn2thc.js","/_next/static/immutable/chunks/1jp6nkbajpbfs.js","/_next/static/immutable/chunks/3jn_lf7v27x-6.js","/_next/static/immutable/chunks/33qq2-hg37d0b.js","/_next/static/immutable/chunks/15isb0svrppbz.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/0asz50g5_lfq9.js","/_next/static/immutable/chunks/30ia-cxa0yoyc.js","/_next/static/immutable/chunks/3ghibkczd0agr.js","/_next/static/immutable/chunks/20mjl75wrar8n.js","/_next/static/immutable/chunks/3nxreg9fiyt2y.js","/_next/static/immutable/chunks/0c04lgvo3p78i.js","/_next/static/immutable/chunks/1u78gf_avpn77.js"],"PaperListPageClient"] 3e:I[70339,["/_next/static/immutable/chunks/355lxm8rh3fxr.js"],"IconMark"] 3c:Tce5,Metabolic dysfunction-associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction-associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis. A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis.3d:Tef4, Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction–associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. Observations The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (&lt;2 standard drinks/d) and for men who consume less than 210 g/wk (&lt;3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis. Conclusions A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis. 28:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Thyroid Hormone Receptor Beta Agonist: Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Thyroid Hormone Receptor Beta Agonist (modality). Clinician-written summaries and actionable practice insights. 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generalizability to cirrhotic disease or other MASH populations is unknown","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.037","tag_type":"warning","value":"SERPINA1 risk genotype results were limited by very small subgroup numbers and could not be meaningfully analyzed","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.037","tag_type":"warning","value":"The study was not powered to detect small genotype-specific differences in resmetirom efficacy; absence of a significant interaction does not conclusively rule out modest differential effects","value_numeric":null}],"summaries":{"what_studied":"A pre-specified analysis of 738 patients from the MAESTRO-NASH phase III RCT (NCT03900429) evaluated whether common MASH risk genotypes (PNPLA3, HSD17B13, TM6SF2, MTARC1, MBOAT7, SERPINA1) — individually or as a composite genetic risk score — modified the efficacy of resmetirom vs. placebo on MASH resolution, fibrosis improvement, MRI-PDFF response, and biomarkers at Week 52.","key_result":"Resmetirom's benefits on MASH resolution, fibrosis improvement, and hepatic steatosis (MRI-PDFF) at Week 52 were not significantly modified by the presence of any individual high-risk genotype or composite genetic risk score; effects were also independent of sex, Hispanic ethnicity, and metabolic risk factors.","limitations":"The substudy was not powered to detect small genotype-specific differences in resmetirom efficacy (n=738); SERPINA1 results could not be fully assessed due to limited sample size; findings are restricted to non-cirrhotic MASH patients.","practice_takeaway":"Clinicians can expect resmetirom's treatment benefits on MASH and fibrosis to hold regardless of a patient's PNPLA3, HSD17B13, TM6SF2, MTARC1, or MBOAT7 risk genotype status. Genetic testing for these variants does not need to inform resmetirom prescribing decisions based on current evidence."}},{"doi":"10.1016/j.jhep.2026.08.028","pmid":"42805503","title":"EASL-EASD-EASO guidance on the use of resmetirom and semaglutide as MASH-targeted therapy","journal_title":"Journal of Hepatology","journal_issn":"0168-8278","published_at":"2026-09-29T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhep.2026.08.028","source_score":39,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-10-01T13:52:41.256Z","updated_at":"2026-10-01T13:52:41.256Z","tags":[{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"brand","value":"Wegovy","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"condition","value":"Hepatic Fibrosis","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"study_design","value":"Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"warning","value":"Long-term data on reduction of hard liver endpoints (cirrhosis, liver cancer, transplantation) for both agents are still awaited from ongoing studies, so benefit-risk estimates may change","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"warning","value":"The guidance explicitly advises against using either agent as MASH-targeted therapy in cirrhosis, but safety data in that population remain limited","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.08.028","tag_type":"warning","value":"This is an expert consensus guidance document, not a systematic review or meta-analysis; individual recommendations are based on regulatory data and expert opinion rather than head-to-head trial evidence","value_numeric":null}],"summaries":{"what_studied":"This joint EASL-EASD-EASO guidance evaluates the use of resmetirom (80mg/100mg orally) and semaglutide (2.4mg subcutaneously weekly) as MASH-targeted therapies in adults with non-cirrhotic MASH and fibrosis stages 2–3, covering patient selection, treatment initiation, monitoring, and discontinuation.","key_result":"Both agents are recommended for adults with non-cirrhotic MASH (fibrosis F2–F3) alongside lifestyle intervention; semaglutide is preferred when obesity, type 2 diabetes, or established cardiovascular disease is present, while resmetirom is prioritized in those without obesity or who are already on or intolerant to GLP-1RAs. Neither agent should be used as MASH-targeted therapy in cirrhosis until further data are available.","limitations":"Recommendations are based on regulatory approval data and expert consensus; long-term effectiveness data reducing major adverse liver-related outcomes (MALO) are still pending from ongoing trials. Evidence supporting use in MASH cirrhosis remains insufficient.","practice_takeaway":"In adults with MASH and fibrosis F2–F3 (confirmed by NITs such as VCTE 10–20 kPa, MRE 3.1–5.0 kPa, or ELF 9.8–11.3, or biopsy), initiate pharmacotherapy alongside lifestyle intervention and optimize comorbidities. Choose semaglutide for patients with obesity, T2D, or high cardiovascular risk, and resmetirom for those without obesity or who cannot tolerate GLP-1RAs; monitor for nutritional status and sarcopenia during semaglutide use."}},{"doi":"10.1016/j.cgh.2026.07.027","pmid":"42776095","title":"AGA Clinical Practice Update on the Evaluation and Management of Metabolic Dysfunction– and Alcohol-Associated Liver Disease: Expert Review","journal_title":"Clinical Gastroenterology and Hepatology","journal_issn":"1542-3565","published_at":"2026-09-23T00:00:00.000Z","url":"https://doi.org/10.1016/j.cgh.2026.07.027","source_score":42,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-29T13:50:09.792Z","updated_at":"2026-09-29T13:50:09.792Z","tags":[{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"condition","value":"Alcohol Use Disorder","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"condition","value":"Metabolic Dysfunction- and Alcohol-Associated Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"condition","value":"Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"modality","value":"Alcohol Use Disorder Pharmacotherapy","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"modality","value":"GIP Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"modality","value":"Noninvasive Fibrosis Assessment","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"modality","value":"Transient Elastography","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"study_design","value":"Expert Review / Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"warning","value":"FDA-approved MASLD therapies (resmetirom, semaglutide) have not been studied in MetALD-specific trials; the GLP-1/GIP data on alcohol craving reduction is described as preliminary only","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"warning","value":"Liver stiffness measurements by elastography can be transiently elevated by active alcohol use, which may lead to fibrosis overestimation if this context is not accounted for in clinical interpretation","value_numeric":null},{"paper_doi":"10.1016/j.cgh.2026.07.027","tag_type":"warning","value":"These Best Practice Advice statements are based on expert opinion and narrative literature review—not systematic review or meta-analysis—so no formal evidence grading or recommendation strength was assigned","value_numeric":null}],"summaries":{"what_studied":"This AGA Clinical Practice Update provides Best Practice Advice (BPA) on the diagnosis, staging, and treatment of metabolic dysfunction– and alcohol-associated liver disease (MetALD), a newly defined category under the 2023 multisociety consensus nomenclature for steatotic liver disease (SLD).","key_result":"Nine BPA statements were issued, covering: classification of MetALD by alcohol intake thresholds (≈140–350 g/wk in women, 210–420 g/wk in men) plus cardiometabolic risk factors; annual alcohol screening; abstinence counseling; tiered noninvasive fibrosis assessment starting with FIB-4; cautious interpretation of elastography during active drinking; micronutrient repletion and exercise; preliminary GLP-1/GIP receptor agonist data suggesting reduced alcohol cravings; pharmacotherapy for alcohol use disorder; and avoidance of bariatric/endobariatric surgery due to insufficient safety data.","limitations":"Systematic reviews were not performed, so BPA statements carry no formal evidence quality ratings or strength-of-recommendation grades. FDA-approved MASLD treatments (resmetirom, semaglutide) have not been formally studied in MetALD populations, leaving a key therapeutic gap.","practice_takeaway":"Classify SLD patients into MetALD using the 140–350 g/wk (women) and 210–420 g/wk (men) alcohol thresholds, screen at least annually with validated tools, and use a tiered FIB-4–first strategy for fibrosis staging. Advise complete alcohol abstinence, replete micronutrients, prescribe aerobic exercise, and offer alcohol use disorder pharmacotherapy for moderate-to-severe AUD; avoid bariatric surgery in MetALD patients."}},{"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":"10.1111/liv.70806","pmid":"42613687","title":"Hepatology: Emerging Paradigms in MASLD, Viral Hepatitis, Cholestatic Liver Disease, Portal Hypertension and Hepatocellular Carcinoma","journal_title":"Liver International","journal_issn":"1478-3223","published_at":"2026-08-18T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13486623/","source_score":16,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-26T06:20:03.789Z","updated_at":"2026-08-26T06:20:03.789Z","tags":[{"paper_doi":"10.1111/liv.70806","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Cirrhosis","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Hepatitis B","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Hepatitis D","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Portal Hypertension","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Primary Biliary Cholangitis","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"condition","value":"Primary Sclerosing Cholangitis","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"generic","value":"bulevirtide","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"Entry Inhibitor","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"FGF21 Analog","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"Incretin-Based Dual/Triple Agonist","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"Pan-PPAR Agonist","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"RNA Silencing Therapy","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"study_design","value":"Narrative Review / Conference Summary","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"warning","value":"Sample size tag omitted as no study-level N is reported.","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"warning","value":"Sex of populations studied is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"warning","value":"Study design label 'Narrative Review / Conference Summary' is an approximation; the article blends review, expert opinion, and guideline highlights without a formal systematic methodology.","value_numeric":null},{"paper_doi":"10.1111/liv.70806","tag_type":"warning","value":"This is a conference proceedings summary, not a primary study — no original patient-level data or statistical outcomes are reported. Level of evidence reflects expert consensus/narrative review only.","value_numeric":null}],"summaries":{"what_studied":"A narrative review of emerging paradigms across major chronic liver diseases — MASLD/MASH, viral hepatitis (HBV/HDV), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), portal hypertension, and hepatocellular carcinoma (HCC) — presented at the Paris International Liver Meeting (January 2026).","key_result":"Resmetirom and semaglutide are now approved for MASH with F2–F3 fibrosis; bulevirtide and novel HBsAg-targeting/RNA-silencing agents are advancing HDV toward functional cure; immunotherapy combinations are achieving unprecedented long-term survival in selected HCC patients; and non-invasive tests have expanded roles in diagnosis, prognosis, and treatment monitoring across all chronic liver diseases.","limitations":"Conference summary with no original primary data; conclusions reflect expert opinion and curated trial highlights rather than a systematic review or meta-analysis. Treatment gaps noted (fewer than half of eligible PBC patients receive second-line therapy) but not quantified with outcome data.","practice_takeaway":"Clinicians managing MASH with F2–F3 fibrosis now have approved disease-modifying options (resmetirom, semaglutide) and should consider non-invasive tests for staging, treatment selection, and monitoring rather than defaulting to biopsy. For HBV and HDV, simplified fibrosis- and viral load–based algorithms with validated biomarkers can guide treatment initiation and safe discontinuation."}},{"doi":"10.1111/apt.70888","pmid":"42527732","title":"Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction‐Associated Steatohepatitis—Reanalysis of Fibrosis Stage 2–3 Subset","journal_title":"Alimentary Pharmacology & Therapeutics","journal_issn":"0269-2813","published_at":"2026-07-29T00:00:00.000Z","url":"https://doi.org/10.1111/apt.70888","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-06T13:22:10.134Z","updated_at":"2026-08-06T13:22:10.134Z","tags":[{"paper_doi":"10.1111/apt.70888","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"condition","value":"Dyslipidemia","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"condition","value":"Hepatic Fibrosis","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"sample_size","value":"n=917","value_numeric":917},{"paper_doi":"10.1111/apt.70888","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"study_design","value":"Post Hoc Analysis of Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"warning","value":"Brand name 'Rezdiffra' inferred from known resmetirom approval; not explicitly stated in the paper.","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"warning","value":"Level of evidence assigned as 2 (RCT-derived data) despite the post hoc nature, which introduces analytic limitations.","value_numeric":null},{"paper_doi":"10.1111/apt.70888","tag_type":"warning","value":"This is a post hoc subgroup analysis and was not prospectively powered for the F2–F3 subset; results should be interpreted as supportive, not independently confirmatory.","value_numeric":null}],"summaries":{"what_studied":"Post hoc analysis of the phase 3 MAESTRO-NASH RCT evaluating once-daily oral resmetirom (80 mg or 100 mg) vs. placebo over 52 weeks in 917 adults with MASH and F2–F3 fibrosis — the label-approved population.","key_result":"MASH resolution was achieved in 25.7% (80 mg) and 29.9% (100 mg) vs. 9.5% placebo (p < 0.0001); fibrosis improvement in 26.5% and 28.9% vs. 17.3% placebo (p < 0.01); LDL-C dropped 11.7–13.7% with resmetirom vs. +2.3% with placebo by Week 24. No new safety signals.","limitations":"Post hoc subgroup analysis of a pre-specified trial, so not powered for this subset; 52-week biopsy endpoints do not confirm long-term outcomes such as cirrhosis prevention or mortality benefit.","practice_takeaway":"For adults with MASH and F2–F3 fibrosis — the FDA-approved indication — resmetirom at both approved doses significantly improves histologic outcomes vs. placebo with a consistent safety profile. Clinicians can expect roughly a 3-fold higher rate of MASH resolution over placebo at 52 weeks."}},{"doi":"10.1016/s2468-1253(26)00077-4","pmid":"42070581","title":"The use of pharmacotherapies in non-cirrhotic metabolic dysfunction-associated steatohepatitis: a UK expert consensus","journal_title":"The Lancet Gastroenterology & Hepatology","journal_issn":"2468-1253","published_at":"2026-05-01T00:00:00.000Z","url":"https://discovery.dundee.ac.uk/en/publications/abbc09aa-8114-4aaf-8c1c-009ab9b94ee0","source_score":37,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-15T13:21:58.193Z","updated_at":"2026-06-15T13:21:58.193Z","tags":[{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"sample_size","value":"n=37","value_numeric":37},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"study_design","value":"Expert Consensus / Delphi Study","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"warning","value":"Brand name tags (Rezdiffra for resmetirom, Ozempic for semaglutide) are inferred from standard drug references; the abstract does not explicitly state brand names.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"warning","value":"Consensus threshold of ≥80% agreement is noted, but individual statement-level agreement rates are not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"warning","value":"Semaglutide's licensing status for MASH specifically may vary by region; the paper implies it is licensed in this context but clinicians should verify local regulatory approval.","value_numeric":null},{"paper_doi":"10.1016/s2468-1253(26)00077-4","tag_type":"warning","value":"The 37 participants refer to Delphi panellists, not a patient cohort — sample_size reflects expert participants, not a clinical trial population.","value_numeric":null}],"summaries":{"what_studied":"A UK expert consensus (Delphi process) developed by the British Association for the Study of the Liver and British Society of Gastroenterology evaluated practical recommendations for pharmacotherapy use—specifically resmetirom and semaglutide—in non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH), covering patient selection, lifestyle management, and follow-up.","key_result":"Consensus (≥80% agreement) was reached on 49 statements; key recommendations include using two-step non-invasive testing (FIB-4 + vibration-controlled transient elastography) to identify presumed F2–F3 fibrosis, treating patients with liver stiffness >10 kPa without cirrhosis, pairing pharmacotherapy with lifestyle intervention, and discontinuing treatment if cirrhosis develops or drug-induced liver injury occurs.","limitations":"Recommendations are based on expert opinion via Delphi consensus (not direct trial evidence), and real-world long-term outcomes data for these agents in MASH are still lacking. The panel is UK-specific, which may limit generalizability to other healthcare systems.","practice_takeaway":"Use FIB-4 followed by transient elastography to identify at-risk MASH patients (liver stiffness >10 kPa, no cirrhosis) as candidates for resmetirom or semaglutide. Start lifestyle behaviour change alongside drug therapy without delaying medication access, and stop treatment if cirrhosis or drug-induced liver injury emerges."}},{"doi":"10.1001/jama.2025.19615","pmid":"41212550","title":"Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults","journal_title":"JAMA","journal_issn":"0098-7484","published_at":"2025-11-10T00:00:00.000Z","url":"https://doi.org/10.1001/jama.2025.19615","source_score":345,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-17","doi":"10.1001/jama.2025.19615","days":"7","issn":"0098-7484","rank":"8","field":"Clinical Medicine","score":"345","category":"Medicine, General & Internal","categories":["Medicine, General & Internal"],"_categories":["Medicine, General & Internal"]},"pubmed":{"doi":"10.1001/jama.2025.19615","title":"Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review.","journal":"JAMA","methods":"","results":"","abstract":"$3c","keywords":[],"pubmed_id":"41212550","conclusions":"","publication_date":"2025-11-10T00:00:00"},"crossref":{"DOI":"10.1001/jama.2025.19615","URL":"https://doi.org/10.1001/jama.2025.19615","ISSN":["0098-7484"],"link":[{"URL":"https://jamanetwork.com/journals/jama/articlepdf/2841071/jama_tilg_2025_rv_250034_1767120330.28927.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"163","type":"journal-article","issue":"2","score":1,"title":["Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults"],"author":[{"given":"Herbert","family":"Tilg","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria"}]},{"given":"Salvatore","family":"Petta","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties Promise, University of Palermo, Palermo, Italy"}]},{"given":"Norbert","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Division of Endocrinology, Diabetology, and Nephrology, University of Tübingen, Tübingen, Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Tübingen, Germany"}]},{"given":"Giovanni","family":"Targher","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Verona, Verona, Italy"},{"name":"Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy"}]}],"issued":{"date-parts":[[2026,1,13]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":"335","created":{"date-time":"2025-11-10T16:30:48Z","timestamp":1762792248000,"date-parts":[[2025,11,10]]},"indexed":{"date-time":"2026-01-20T05:46:55Z","timestamp":1768888015289,"date-parts":[[2026,1,20]]},"subject":[],"abstract":"$3d","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jama/fullarticle/2841071"}},"subtitle":["A Review"],"deposited":{"date-time":"2026-01-13T16:00:35Z","timestamp":1768320035000,"date-parts":[[2026,1,13]]},"issn-type":[{"type":"print","value":"0098-7484"}],"published":{"date-parts":[[2026,1,13]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.1016/S0140-6736(24)01811-7","key":"jrv250034r1","year":"2024","issue":"10464","author":"Israelsen","volume":"404","first-page":"1761","unstructured":null,"article-title":"Steatotic liver 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Start with weight loss (hypocaloric low-carbohydrate and low-fat diet), physical exercise, and alcohol avoidance; optimize diabetes, obesity, hypertension, and lipid control; consider bariatric surgery if BMI >35; resmetirom and subcutaneous semaglutide are conditionally FDA-approved for adults with MASH and moderate to advanced fibrosis."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Thyroid Hormone Receptor Beta Agonist"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Thyroid Hormone Receptor Beta Agonist"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Thyroid Hormone Receptor Beta Agonist"}}}]] 2b:null

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