{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:06:14Z","timestamp":1792512374479,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. Menopause is associated with increased hepatic fat deposition and thus metabolic dysfunction, contributing to heightened risk of progressive liver and cardiovascular disease. Hormone replacement therapy (HRT), supported by pre\u2010clinical data, may be associated with a lower risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort study using the TriNetX global federated research network. Eligible participants were peri\u2010menopausal women (ICD\u201010 codes N95\/Z78.0, AND age 40\u201365\u2009years) with pre\u2010existing MASLD (based on ICD\u201010 codes K76.0\/K75.81 or positive modified hepatic steatosis index plus \u2265\u20091 metabolic syndrome, MetS, trait). Patients initiating HRT (oestrogen \u00b1 progesterone) were compared with untreated controls using 1:1 propensity score matching for demographics, comorbidities, biochemistry and medications. The primary outcome was a composite of major adverse liver outcomes (MALO: portal hypertension, varices, ascites, spontaneous bacterial peritonitis, encephalopathy, hepatorenal\/pulmonary syndromes, cirrhosis, decompensated liver disease, hepatocellular carcinoma, liver transplant). Secondary outcomes were individual MALO components, type 2 diabetes (T2D), major adverse cardiovascular events (MACE), breast and endometrial cancer, and venous thromboembolism (VTE). Cox regression generated hazard ratios (HRs) with 95% CIs over 5\u2009years. Sensitivity analyses adjusted for geography, hormone type, and degree of obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After matching, 21\u2009639 patients were included in each treatment arm. HRT was associated with a significantly reduced risk of MALO (HR 0.80; 0.71, 0.9), largely driven by reductions in ascites and SBP (0.78; 0.64, 0.95), and liver cirrhosis (0.75; 0.63, 0.90), and reduced risk of cardiometabolic outcomes: T2D (0.90; 0.84, 0.96), and MACE (0.90; 0.83, 0.98). HRT was not associated with increased risk of breast cancer or VTE, whilst endometrial cancer risk was reduced (0.49; 0.40, 0.61). Oestrogen was linked to greater benefits compared to progesterone, and patients with mild\u2013moderate obesity experienced more significant risk reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Treatment of peri\u2010menopausal symptoms with HRT, in patients with pre\u2010existing MASLD, is associated with a lower 5\u2010year risk of major liver and cardiometabolic disease. These findings support early basic science research and should prompt a closer examination through clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70562","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:35:51Z","timestamp":1772966151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of Hormone Replacement Therapy on Liver and Cardiometabolic Outcomes in Peri\u2010Menopausal\n                    <scp>MASLD<\/scp>"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex E.","family":"Henney","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Centre for Musculoskeletal Research, Faculty of Biology Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6128-0822","authenticated-orcid":false,"given":"Daniel J.","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism and Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2024.0431"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.02.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94189-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/757461"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00634-7"},{"key":"e_1_2_10_7_1","unstructured":"FDA \u201cFDA Approves Treatment for Serious Liver Disease Known as \u2018MASH\u2019 2025 \u201d(2025) 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