{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:52:38Z","timestamp":1780624358032,"version":"3.54.1"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T00:00:00Z","timestamp":1479945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Patients with chronic liver disease sometimes develop cholestasis, which induces severe whole\u2010body pruritus that may disrupt daily activities and sleep. To determine the efficacy of nalfurafine hydrochloride (5\u00a0\u03bcg), which is a selective \u03ba\u2010opioid receptor agonist, in improving pruritus, we undertook a double\u2010blind placebo\u2010controlled study in patients with chronic liver disease with refractory pruritus. Nalfurafine hydrochloride at 2.5\u00a0\u03bcg was also used to evaluate the dose\u2013response relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 318 subjects were randomly assigned to receive the placebo or nalfurafine hydrochloride (2.5 or 5\u00a0\u03bcg) given orally once daily for 84 consecutive days. Pruritus was assessed based on the visual analog scale and pruritus scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Changes in the visual analog scale at week 4 (last observation carried forward) were significantly greater in the nalfurafine hydrochloride groups at 28.56 and 27.46\u00a0mm in the 2.5\u00a0\u03bcg and 5\u00a0\u03bcg groups, respectively, compared to 19.25\u00a0mm in the placebo group (<jats:italic>P<\/jats:italic>\u2009=\u20090.0022 and 0.0056, respectively). The major adverse drug reactions (ADRs) included pollakiuria (including nocturia), somnolence, insomnia (including middle insomnia), and constipation. Most ADRs were mild.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nalfurafine hydrochloride (2.5 or 5\u00a0\u03bcg daily) was effective in the treatment of refractory pruritus in patients with chronic liver disease. Furthermore, no clinically significant ADRs were observed at either dose.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12830","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T11:26:55Z","timestamp":1476790015000},"page":"972-982","source":"Crossref","is-referenced-by-count":90,"title":["Efficacy of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus: A randomized, double\u2010blind trial"],"prefix":"10.1111","volume":"47","author":[{"given":"Hiromitsu","family":"Kumada","sequence":"first","affiliation":[{"name":"Department of Hepatology Toranomon Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Miyakawa","sequence":"additional","affiliation":[{"name":"The 4th Department of Internal Medicine Teikyo University School of Medicine, Mizonokuchi Hospital  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ando","sequence":"additional","affiliation":[{"name":"Toray Industries, Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Oh","sequence":"additional","affiliation":[{"name":"Toray Industries, Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Takamori","sequence":"additional","affiliation":[{"name":"Juntendo University Urayasu Hospital  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetomo","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine Saitama Medical University Hospital  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,24]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"616","article-title":"Itching in hepatic disorder and opioid","volume":"197","author":"Tohda C","year":"2001","journal-title":"J Clin Experiment Med"},{"key":"e_1_2_6_3_1","first-page":"76","volume-title":"Itching Qs & As","author":"Izaki S","year":"1997"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290450"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1089-3261(03)00105-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1993.tb01510.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2003.08.007"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840110526"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00369-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.46.366"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01588-6"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp588"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341268"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800600817"},{"key":"e_1_2_6_15_1","first-page":"185","article-title":"Some aspects of the experimental induction and measurement of itch","volume":"69","author":"Wahlgren CF","year":"1989","journal-title":"Acta Derm Venereol"},{"key":"e_1_2_6_16_1","first-page":"692","article-title":"Evaluation of itch based on a new rating scale using patient diary","volume":"56","author":"Kawashima M","year":"2002","journal-title":"Jpn J Clin Dermatol"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2003.05293.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2009.03906.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i47.17877"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhepr.12830","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhepr.12830","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.12830","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T03:24:34Z","timestamp":1696303474000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.12830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,24]]},"references-count":18,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1111\/hepr.12830"],"URL":"https:\/\/doi.org\/10.1111\/hepr.12830","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,24]]}}}