{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:41:07Z","timestamp":1787316067373,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"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":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>No pharmacologic treatment has yet been approved for sleep disturbances in cirrhosis, a high\u2010risk group with substantial prevalence and clinical consequences. Lemborexant has shown efficacy for insomnia, but evidence in cirrhosis is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Restoring Sleep in End\u2010Stage Liver Disease (RESTORE) is a prospective, double\u2010blind, placebo\u2010controlled, crossover trial of Lemborexant for patients with cirrhosis in Cipto Mangunkusumo National Referral Hospital. We randomized 82 patients into three arms: Placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200928), 5\u2009mg Lemborexant (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200928), and 10\u2009mg Lemborexant (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200926). Efficacy was assessed via Pittsburgh Sleep Quality Index (PSQI) over a 2\u2010week period. Safety was evaluated using the EncephalApp Stroop Test for hepatic encephalopathy and liver function tests including AST, ALT, and total bilirubin. PSQI was reevaluated post\u2010crossover at week 4 to investigate rebound insomnia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lemborexant significantly reduced PSQI at week 2 in both 5\u2009mg (MD: \u22127.0\u2009\u00b1\u20093.15;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 10\u2009mg groups (MD: \u22128.27\u2009\u00b1\u20092.68;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), indicating better sleep quality. The 5\u2009mg group showed improved Stroop Test reaction time (MD: \u221223.5\u2009\u00b1\u200931.3;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), suggesting better cognitive function, whereas 10\u2009mg showed a mild but significant increase in reaction time (MD: 16.7\u2009\u00b1\u200941.3; p\u2009=\u20090.048). Liver function was not different across treatment groups. Post\u2010crossover analysis showed persistent low PSQI scores in active groups who were switched to placebo. Patients who initially received placebo demonstrated improved sleep after receiving Lemborexant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study supported the efficacy and safety of Lemborexant, particularly at 5\u2009mg, against sleep problems in cirrhosis. Larger studies with longer follow\u2010up are warranted to strengthen evidence. ClinicalTrials.gov: NCT07480096.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70811","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:23:36Z","timestamp":1783481016000},"page":"458-470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical Trial: Lemborexant Efficacy and Safety in Liver Cirrhosis\u2014Randomized, Double\u2010Blind, Crossover Clinical Trial"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4009-7938","authenticated-orcid":false,"given":"Rino Alvani","family":"Gani","sequence":"first","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9537-6112","authenticated-orcid":false,"given":"Pitt","family":"Akbar","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6702-2659","authenticated-orcid":false,"given":"Irsan","family":"Hasan","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3455-6547","authenticated-orcid":false,"given":"Andri Sanityoso","family":"Sulaiman","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-9968","authenticated-orcid":false,"given":"Cosmas Rinaldi Adithya","family":"Lesmana","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-169X","authenticated-orcid":false,"given":"Juferdy","family":"Kurniawan","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Melissa","family":"Panjaitan","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-7742","authenticated-orcid":false,"given":"Valerie Josephine","family":"Dirjayanto","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Internal Medicine Department Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(21)00169\u20102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.01.027"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcdt.2012.09.012"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast\u20102018\u2010000271"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572\u20100241.2006.01028.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574886311308030011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010016\u20109944\u20105"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2019.01.109"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa123"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0271901"},{"key":"e_1_2_11_12_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use \u201cICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6 (R1) \u201dPublished online June 10 1996 https:\/\/apps.who.int\/medicinedocs\/documents\/s22154en\/s22154en.pdf."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"e_1_2_11_14_1","unstructured":"R. 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