{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T23:42:05Z","timestamp":1769557325102,"version":"3.49.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Govt. of India"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Nonalcoholic fatty liver disease (NAFLD) is a complex disease which is characterized by the deposition of fats in the hepatocytes. Further, it progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD urges to find the non-invasive predictive biomarkers. In this study, we sought to determine increased BMP8B levels as predictors for the progression of NAFLD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In the present cross-sectional study, circulatory BMP8B levels were measured in healthy controls (n = 56), NAFL patients (n = 72) and NASH patients (n = 77) by using an ELISA kit. Human hepatic BMP8B mRNA expression was measured in the liver tissue of control and NASH patients. In addition, BMP8B expression was confirmed by immunohistochemistry analysis. Furthermore, hepatic BMP8B mRNA expression was measured in wild type (WT) mice, WT mice fed with choline deficient high fat diet (WT+CDHF), iNOS (inducible nitric oxide synthase) knockout (iNOS-\/-) mice, iNOS-\/- fed with CDHF diet (iNOS-\/-+CDHF).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Increased circulatory BMP8B levels and BMP8B mRNA expression in hepatic tissue were significantly higher in NASH patients as compared with the control subjects. BMP8B expression was increased parallel to the fibrosis score in the hepatic tissues of NASH patients. It was observed that increased BMP8B levels have shown a significant positive correlation between aspartate aminotransferase (r = 0.31, p = 0.005), alanine aminotransferase (r = 0.23, p = 0.045), APRI (r = 0.30, p = 0.009), and Fib-4 score (r = 0.25, p = 0.036) in NASH patients. BMP8B has maintained a significant association with NASH and shown high sensitivity (92.91%) and specificity (92.73%) in NASH patients. Furthermore, increased BMP8B mRNA expression levels were observed in iNOS-\/-+CDHF mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our study findings confirmed that BMP8B increases with the severity of the disease and BMP8B shows potential as a non-invasive predictive biomarker to identify NAFLD progression. However, future studies should investigate circulatory BMP8B levels in a large number of patients and also its impact on liver during NAFLD progression.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0295839","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T18:55:35Z","timestamp":1703184935000},"page":"e0295839","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Circulatory bone morphogenetic protein (BMP) 8B is a non-invasive predictive biomarker for the diagnosis of non-alcoholic steatohepatitis (NASH)"],"prefix":"10.1371","volume":"18","author":[{"given":"Nadella","family":"Mounika","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angeera","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parul","family":"Kamboj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay K.","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Utpal Jyoti","family":"Deka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savneet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-2557","authenticated-orcid":true,"given":"Ramu","family":"Adela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"issue":"1","key":"pone.0295839.ref001","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention.","volume":"15","author":"Z Younossi","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"5","key":"pone.0295839.ref002","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1053\/gast.2002.36572","article-title":"American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease","volume":"123","author":"AJ Sanyal","year":"2022","journal-title":"Gastroenterology"},{"issue":"6","key":"pone.0295839.ref003","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","article-title":"Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis","volume":"10","author":"QM Anstee","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol."},{"issue":"4","key":"pone.0295839.ref004","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/flgastro-2013-100404","article-title":"Non-alcoholic fatty liver disease: a practical approach to treatment.","volume":"5","author":"JK Dyson","year":"2014","journal-title":"Frontline Gastroenterol."},{"key":"pone.0295839.ref005","doi-asserted-by":"crossref","first-page":"d3897","DOI":"10.1136\/bmj.d3897","article-title":"How big a problem is non-alcoholic fatty liver disease?","volume":"343","author":"QM Anstee","year":"2011","journal-title":"BMJ"},{"issue":"1","key":"pone.0295839.ref006","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12876-018-0843-6","article-title":"Metabolic syndrome and biochemical changes among non-alcoholic fatty liver disease patients attending a tertiary care hospital of Nepal","volume":"18","author":"BD Pardhe","year":"2018","journal-title":"BMC Gastroenterol"},{"key":"pone.0295839.ref007","doi-asserted-by":"crossref","first-page":"145754","DOI":"10.1155\/2012\/145754","article-title":"Diagnosis and evaluation of nonalcoholic fatty liver disease","volume":"2012","author":"M Obika","year":"2012","journal-title":"Exp Diabetes Res"},{"issue":"27","key":"pone.0295839.ref008","first-page":"9026","article-title":"Role of liver biopsy in nonalcoholic fatty liver disease","volume":"20","author":"IL Nalbantoglu","year":"2014","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pone.0295839.ref009","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jceh.2019.09.006","article-title":"NonInvasive Biomarkers in Nonalcoholic Fatty Liver Disease: Are We There Yet?","volume":"10","author":"SP Singh","year":"2020","journal-title":"J Clin Exp Hepatol."},{"issue":"5","key":"pone.0295839.ref010","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2018.12.036","article-title":"Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease","volume":"156","author":"L Castera","year":"2019","journal-title":"Gastroenterology"},{"issue":"7","key":"pone.0295839.ref011","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S2468-1253(23)00066-3","article-title":"Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis","volume":"8","author":"MA Tincopa","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"1\u20132","key":"pone.0295839.ref012","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1159\/000318741","article-title":"Obesity affects the liver\u2014the link between adipocytes and hepatocytes","volume":"83","author":"A Wree","year":"2011","journal-title":"Digestion"},{"issue":"6","key":"pone.0295839.ref013","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s42255-020-0214-9","article-title":"Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis.","volume":"2","author":"M Vacca","year":"2020","journal-title":"Nat Metab."},{"issue":"4","key":"pone.0295839.ref014","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/08977190412331279890","article-title":"Bone Morphogenetic Proteins.","volume":"22","author":"Di Chen","year":"2004","journal-title":"Growth Factors"},{"issue":"1","key":"pone.0295839.ref015","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/dvg.1020170109","article-title":"Ventral mesodermal patterning in Xenopus embryos: expression patterns and activities of BMP-2 and BMP-4","volume":"17","author":"A. 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