{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T04:51:11Z","timestamp":1794199871966,"version":"4.8.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although transplantation is the only definitive treatment for liver cirrhosis, there remains a shortage of donors, necessitating that novel treatments be developed. We aimed to establish a liver fibrosis model in <jats:italic>Macaca fascicularis<\/jats:italic> that can help accelerate preclinical research. Liver fibrosis was induced by administering thioacetamide (TAA) and carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). Analysis of residual liver function and fibrosis progression was based on clinical indices, such as the Child\u2013Pugh score or fibrotic markers, besides histology. TAA-induced marked fibrosis, whereas CCl<jats:sub>4<\/jats:sub> did not induce fibrosis. Concerning residual liver function, both of TAA and CCl<jats:sub>4<\/jats:sub> worsened the indices of the Child\u2013Pugh score, but only the TAA model increased the retention ratio of indocyanine green. The TAA-induced fibrosis model in <jats:italic>Macaca fascicularis<\/jats:italic> worsens fibrosis and residual liver function, mimicking Child\u2013Pugh grade B. Given that our model was evaluated by clinical indices, it could be applicable to preclinical research.<\/jats:p>","DOI":"10.1038\/s41598-020-58739-4","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T11:03:58Z","timestamp":1581505438000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel liver fibrosis model in Macaca fascicularis induced by thioacetamide"],"prefix":"10.1038","volume":"10","author":[{"given":"Megumi","family":"Matsuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Hatada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Ohtsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"58739_CR1","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1111\/liv.12818","volume":"35","author":"JW Park","year":"2015","unstructured":"Park, J. W. et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: The BRIDGE Study. Liver Int. 35, 2155\u20132166 (2015).","journal-title":"Liver Int."},{"key":"58739_CR2","doi-asserted-by":"publisher","first-page":"S60","DOI":"10.1016\/j.clinre.2015.06.015","volume":"39","author":"M Sun","year":"2015","unstructured":"Sun, M. & Kisseleva, T. Reversibility of liver fibrosis. Clin. Res. Hepatol. Gastroenterol. 39, S60\u2013S63 (2015).","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"58739_CR3","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1002\/hep.28316","volume":"63","author":"JC Lai","year":"2016","unstructured":"Lai, J. C., Dodge, J. L., Sen, S., Covinsky, K. & Feng, S. Functional decline in patients with cirrhosis awaiting liver transplantation: Results from the functional assessment in liver transplantation (FrAILT) study. Hepatology 63, 574\u2013580 (2016).","journal-title":"Hepatology"},{"key":"58739_CR4","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/labinvest.2008.91","volume":"88","author":"R Salguero Palacios","year":"2008","unstructured":"Salguero Palacios, R. et al. Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. Lab. Investig. 88, 1192\u20131203 (2008).","journal-title":"Lab. Investig."},{"key":"58739_CR5","doi-asserted-by":"publisher","first-page":"3821","DOI":"10.1111\/jcmm.13304","volume":"21","author":"J George","year":"2017","unstructured":"George, J., Tsutsumi, M. & Tsuchishima, M. MMP-13 deletion decreases profibrogenic molecules and attenuates N-nitrosodimethylamine-induced liver injury and fibrosis in mice. J. Cell. Mol. Med. 21, 3821\u20133835 (2017).","journal-title":"J. Cell. Mol. Med."},{"key":"58739_CR6","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.scr.2016.08.013","volume":"17","author":"DA Grow","year":"2016","unstructured":"Grow, D. A., McCarrey, J. R. & Navara, C. S. Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson\u2019s disease. Stem Cell Res. 17, 352\u2013366 (2016).","journal-title":"Stem Cell Res."},{"key":"58739_CR7","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1038\/nm.2038","volume":"15","author":"RW Wiseman","year":"2009","unstructured":"Wiseman, R. W. et al. Major histocompatibility complex genotyping with massively parallel pyrosequencing. Nat. Med. 15, 1322\u20131326 (2009).","journal-title":"Nat. Med."},{"key":"58739_CR8","first-page":"313","volume":"18","author":"T Rivera-Hernandez","year":"2014","unstructured":"Rivera-Hernandez, T. et al. The contribution of non-human primate models to the development of human vaccines. Discov Med 18, 313\u201322 (2014).","journal-title":"Discov Med"},{"key":"58739_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/cshperspect.a015503","volume":"3","author":"DJ Anderson","year":"2013","unstructured":"Anderson, D. J. & Kirk, A. D. Primate Models in organ transplantation. Cold Spring Harb. Perspect. Med. 3, 1\u201318 (2013).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"58739_CR10","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.etp.2014.03.003","volume":"66","author":"K Ding","year":"2014","unstructured":"Ding, K. et al. Establishment of a liver fibrosis model in cynomolgus monkeys. Exp. Toxicol. Pathol. 66, 257\u2013261 (2014).","journal-title":"Exp. Toxicol. Pathol."},{"key":"58739_CR11","first-page":"1","volume":"3","author":"S Ding","year":"2018","unstructured":"Ding, S. et al. CCl4 Induced Liver Fibrosis Model in Cynomolgus Monkeys. M J Vert. 3, 1\u20138 (2018).","journal-title":"M J Vert."},{"key":"58739_CR12","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1538\/expanim.17-0156","volume":"67","author":"T INOUE","year":"2018","unstructured":"INOUE, T. et al. Thioacetamide-induced hepatic fibrosis in the common marmoset. Exp. Anim. 67, 321\u2013327 (2018).","journal-title":"Exp. Anim."},{"key":"58739_CR13","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jhep.2004.11.015","volume":"42","author":"F Durand","year":"2005","unstructured":"Durand, F. & Valla, D. Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J. Hepatol. 42, 100\u2013107 (2005).","journal-title":"J. Hepatol."},{"key":"58739_CR14","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1007\/s00535-006-1878-y","volume":"41","author":"I Ikai","year":"2006","unstructured":"Ikai, I. et al. A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma. J. Gastroenterol. 41, 884\u2013892 (2006).","journal-title":"J. Gastroenterol."},{"key":"58739_CR15","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1053\/jhep.2001.22172","volume":"33","author":"PS Kamath","year":"2001","unstructured":"Kamath, P. S. et al. A model to predict survival in patients with end-stage liver disease. Hepatology 33, 464\u2013470 (2001).","journal-title":"Hepatology"},{"key":"58739_CR16","doi-asserted-by":"publisher","first-page":"8660","DOI":"10.3748\/wjg.v20.i26.8660","volume":"20","author":"YQ Bai","year":"2014","unstructured":"Bai, Y. Q. et al. Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis. World J. Gastroenterol. 20, 8660\u20138666 (2014).","journal-title":"World J. Gastroenterol."},{"key":"58739_CR17","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.dld.2017.12.015","volume":"50","author":"Y Cheng","year":"2018","unstructured":"Cheng, Y. et al. Sorafenib and fluvastatin synergistically alleviate hepatic fibrosis via inhibiting the TGF\u03b21\/Smad3 pathway. Dig. Liver Dis. 50, 381\u2013388 (2018).","journal-title":"Dig. Liver Dis."},{"key":"58739_CR18","doi-asserted-by":"publisher","first-page":"S242","DOI":"10.1016\/S0168-8278(18)30701-3","volume":"68","author":"N Sakamoto","year":"2018","unstructured":"Sakamoto, N. et al. Clinical phase 1b study results for safety, pharmacokinetics and efficacy of ND-L02-s0201, a novel targeted lipid nanoparticle delivering HSP47 SIRNA for the treatment of Japanese patients with advanced liver fibrosis. J. Hepatol. 68, S242 (2018).","journal-title":"J. Hepatol."},{"key":"58739_CR19","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s11948-015-9659-8","volume":"22","author":"HJ Curzer","year":"2016","unstructured":"Curzer, H. J., Perry, G., Wallace, M. C. & Perry, D. The Three Rs of Animal Research: What they Mean for the Institutional Animal Care and Use Committee and Why. Sci. Eng. Ethics 22, 549\u2013565 (2016).","journal-title":"Sci. Eng. Ethics"},{"key":"58739_CR20","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1136\/gut.48.4.548","volume":"48","author":"R Issa","year":"2001","unstructured":"Issa, R. et al. Apoptosis of hepatic stellate cells: Involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut 48, 548\u2013557 (2001).","journal-title":"Gut"},{"key":"58739_CR21","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/S0928-4346(96)00325-8","volume":"6","author":"F Ichida","year":"1996","unstructured":"Ichida, F. et al. New Inuyama classification; new criteria for histological assessment of chronic hepatitis. Int. Hepatol. Commun. 6, 112\u2013119 (1996).","journal-title":"Int. Hepatol. Commun."},{"key":"58739_CR22","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/S0140-6736(96)07642-8","volume":"349","author":"T Poynard","year":"1997","unstructured":"Poynard, T., Bedossa, P. & Opolon, P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 349, 825\u201332 (1997).","journal-title":"Lancet"},{"key":"58739_CR23","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/0003-9861(61)90291-0","volume":"93","author":"JF Woessner","year":"1961","unstructured":"Woessner, J. F. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch. Biochem. Biophys. 93, 440\u2013447 (1961).","journal-title":"Arch. Biochem. Biophys."},{"key":"58739_CR24","first-page":"253","volume":"18","author":"K Patel","year":"2003","unstructured":"Patel, K. et al. Clinical use of hyaluronic acid as a predictor of fibrosis change in hepatitis C. J. Gastroenterol. Hepatol. 18, 253\u2013257 (2003).","journal-title":"Hepatol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58739-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58739-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58739-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T06:56:05Z","timestamp":1670309765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58739-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,12]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["58739"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-58739-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,12]]},"assertion":[{"value":"4 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2450"}}