{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:30:43Z","timestamp":1780763443414,"version":"3.54.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061713"],"award-info":[{"award-number":["U01DK061713"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061718"],"award-info":[{"award-number":["U01DK061718"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061728"],"award-info":[{"award-number":["U01DK061728"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061732"],"award-info":[{"award-number":["U01DK061732"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061734"],"award-info":[{"award-number":["U01DK061734"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061737"],"award-info":[{"award-number":["U01DK061737"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061738"],"award-info":[{"award-number":["U01DK061738"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01DK061730"],"award-info":[{"award-number":["U01DK061730"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U24DK061730"],"award-info":[{"award-number":["U24DK061730"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000439"],"award-info":[{"award-number":["UL1TR000439"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000077"],"award-info":[{"award-number":["UL1TR000077"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000436"],"award-info":[{"award-number":["UL1TR000436"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000150"],"award-info":[{"award-number":["UL1TR000150"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000424"],"award-info":[{"award-number":["UL1TR000424"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000006"],"award-info":[{"award-number":["UL1TR000006"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000448"],"award-info":[{"award-number":["UL1TR000448"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000040"],"award-info":[{"award-number":["UL1TR000040"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000100"],"award-info":[{"award-number":["UL1TR000100"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000004"],"award-info":[{"award-number":["UL1TR000004"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000423"],"award-info":[{"award-number":["UL1TR000423"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002649"],"award-info":[{"award-number":["UL1TR002649"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000454"],"award-info":[{"award-number":["UL1TR000454"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Portal inflammation (PI) and ductular reaction (DR) in metabolic dysfunction-associated steatotic liver disease (MASLD) have shown associations with disease severity. We developed a histologic categorization of these features to correlate with known features of MASLD. This study proposes a scoring schema for PI, PP and DR, and relates them to histologic and clinical features in children and adults. This expanded scoring system was developed to identify clinically relevant categories and defined criteria for scoring biopsies. In adults (N:483), more severe PI, PP, and DR were associated with older age (<jats:italic>p<\/jats:italic>\u2009\u2264 0.002), and PP and DR were associated with increased alkaline phosphatase (ALP) (<jats:italic>p<\/jats:italic>\u2009\u2264 0.003), GGT (<jats:italic>p<\/jats:italic>\u2009\u2264 0.001), and total bilirubin (<jats:italic>p<\/jats:italic>\u2009\u2264 0.01). More severe PI, PP, and DR were associated with higher NAFLD activity score (NAS), fibrosis stage, and diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) (<jats:italic>p<\/jats:italic>\u2009\u2264 0.05). In children (N:151), PP and DR were associated with younger age (<jats:italic>p<\/jats:italic>\u2009\u2264 0.0001), and elevated AST, ALT, and ALP (<jats:italic>p<\/jats:italic>\u2009\u2264 0.05). More severe PI, PP, and DR were associated with advanced fibrosis stage, and PP and DR were associated with diagnosis of borderline or definite MASH in children (<jats:italic>p<\/jats:italic>\u2009\u2264 0.05). From multivariable ordinal logistic regression analysis, a higher fibrosis stage was independently associated with more severe PI in both adults and children. Interobserver agreement was substantial for PI, PP and DR. The proposed scoring system demonstrated reproducibility and associations between more severe portal-based disease and advanced liver histology, age, and elevated liver enzymes in adults and children. Evaluation of portal disease could provide insight into therapeutic response and disease progression.<\/jats:p>","DOI":"10.1007\/s00428-025-04087-5","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T14:34:45Z","timestamp":1744295685000},"page":"363-376","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical associations of portal-based disease in MASLD: proposal of a new histological scoring system"],"prefix":"10.1007","volume":"487","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-8269","authenticated-orcid":false,"given":"Daniela S.","family":"Allende","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Guy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Carpenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Cummings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Contos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Belt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Van Natta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Behling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the NASH Clinical Research Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"issue":"9","key":"4087_CR1","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","volume":"94","author":"EM Brunt","year":"1999","unstructured":"Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94(9):2467\u201374. https:\/\/doi.org\/10.1111\/j.1572-0241.1999.01377.x","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"4087_CR2","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1002\/hep.24268","volume":"53","author":"ZM Younossi","year":"2011","unstructured":"Younossi ZM, Stepanova M, Rafiq N, Makhlouf H, Younoszai Z, Agrawal R, Goodman Z (2011) Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 53(6):1874\u201382. https:\/\/doi.org\/10.1002\/hep.24268","journal-title":"Hepatology"},{"issue":"2","key":"4087_CR3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","volume":"149","author":"P Angulo","year":"2015","unstructured":"Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Keach JC, Lafferty HD, Stahler A, Haflidadottir S, Bendtsen F (2015) Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149(2):389\u201397.e10. https:\/\/doi.org\/10.1053\/j.gastro.2015.04.043","journal-title":"Gastroenterology"},{"issue":"11","key":"4087_CR4","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1111\/hepr.12656","volume":"46","author":"S Ballestri","year":"2016","unstructured":"Ballestri S, Nascimbeni F, Romagnoli D, Lonardo A (2016) The independent predictors of non-alcoholic steatohepatitis and its individual histological features: insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment. Hepatol Res 46(11):1074\u20131087. https:\/\/doi.org\/10.1111\/hepr.12656","journal-title":"Hepatol Res"},{"issue":"4","key":"4087_CR5","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1002\/hep.21327","volume":"44","author":"M Ekstedt","year":"2006","unstructured":"Ekstedt M, Franz\u00e9n LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S (2006) Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44(4):865","journal-title":"Hepatology"},{"issue":"3","key":"4087_CR6","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1002\/hep.22724","volume":"49","author":"EM Brunt","year":"2009","unstructured":"Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE, Lavine JE, Neuschwander-Tetri BA, NASH Clinical Research Network- a list of members of the Nonalcoholic Steatohepatitis Clinical Research Network can be found in the Appendix (2009) Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 49(3):809\u201320. https:\/\/doi.org\/10.1002\/hep.22724","journal-title":"Hepatology"},{"issue":"9","key":"4087_CR7","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1136\/jcp.2010.079145","volume":"63","author":"EA Rakha","year":"2010","unstructured":"Rakha EA, Adamson L, Bell E, Neal K, Ryder SD, Kaye PV, Aithal GP (2010) Portal inflammation is associated with advanced histological changes in alcoholic and non-alcoholic fatty liver disease. J Clin Pathol 63(9):790\u20135. https:\/\/doi.org\/10.1136\/jcp.2010.079145","journal-title":"J Clin Pathol"},{"issue":"5","key":"4087_CR8","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/hep.1840010511","volume":"1","author":"RG Knodell","year":"1981","unstructured":"Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J (1981) Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1(5):431\u20135. https:\/\/doi.org\/10.1002\/hep.1840010511","journal-title":"Hepatology"},{"issue":"3","key":"4087_CR9","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/0168-8278(91)90084-o","volume":"13","author":"PJ Scheuer","year":"1991","unstructured":"Scheuer PJ (1991) Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 13(3):372\u20134. https:\/\/doi.org\/10.1016\/0168-8278(91)90084-o","journal-title":"J Hepatol"},{"issue":"12","key":"4087_CR10","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1097\/00000478-199512000-00007","volume":"19","author":"KP Batts","year":"1995","unstructured":"Batts KP, Ludwig J (1995) Chronic hepatitis.An update on terminology and reporting. Am J Surg Pathol 19(12):1409\u201317. https:\/\/doi.org\/10.1097\/00000478-199512000-00007","journal-title":"Am J Surg Pathol"},{"issue":"6","key":"4087_CR11","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","volume":"22","author":"K Ishak","year":"1995","unstructured":"Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN et al (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22(6):696\u20139. https:\/\/doi.org\/10.1016\/0168-8278(95)80226-6","journal-title":"J Hepatol"},{"issue":"6","key":"4087_CR12","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ, Nonalcoholic Steatohepatitis Clinical Research Network (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41(6):1313\u201321. https:\/\/doi.org\/10.1002\/hep.20701","journal-title":"Hepatology"},{"issue":"3","key":"4087_CR13","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1002\/hep.28374","volume":"63","author":"JP Mann","year":"2016","unstructured":"Mann JP, De Vito R, Mosca A, Alisi A, Armstrong MJ, Raponi M, Baumann U, Nobili V (2016) Portal inflammation is independently associated with fibrosis and metabolic syndrome in pediatric nonalcoholic fatty liver disease. Hepatology 63(3):745\u201353. https:\/\/doi.org\/10.1002\/hep.28374","journal-title":"Hepatology"},{"issue":"4","key":"4087_CR14","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1002\/hep.26937","volume":"59","author":"VL Gadd","year":"2014","unstructured":"Gadd VL, Skoien R, Powell EE, Fagan KJ, Winterford C, Horsfall L, Irvine K, Clouston AD (2014) The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology 59(4):1393\u2013405. https:\/\/doi.org\/10.1002\/hep.26937","journal-title":"Hepatology"},{"issue":"8","key":"4087_CR15","doi-asserted-by":"publisher","first-page":"e104558","DOI":"10.1371\/journal.pone.0104558","volume":"9","author":"N Alkhouri","year":"2014","unstructured":"Alkhouri N, Mansoor S, Giammaria P, Liccardo D, Lopez R, Nobili V (2014) The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease. PLoS One 9(8):e104558. https:\/\/doi.org\/10.1371\/journal.pone.0104558","journal-title":"PLoS One"},{"issue":"18","key":"4087_CR16","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","volume":"362","author":"AJ Sanyal","year":"2010","unstructured":"Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362(18):1675\u201385. https:\/\/doi.org\/10.1056\/NEJMoa0907929","journal-title":"N Engl J Med"},{"issue":"9972","key":"4087_CR17","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/S0140-6736(14)61933-4","volume":"385","author":"BA Neuschwander-Tetri","year":"2015","unstructured":"Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E, NASH Clinical Research Network (2015) Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385(9972):956\u201365. https:\/\/doi.org\/10.1016\/S0140-6736(14)61933-4","journal-title":"Lancet"},{"issue":"2","key":"4087_CR18","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/hep.30418","volume":"70","author":"EM Brunt","year":"2019","unstructured":"Brunt EM, Kleiner DE, Wilson LA, Sanyal AJ, Neuschwander-Tetri BA, Nonalcoholic Steatohepatitis Clinical Research Network (2019) Improvements in histologic features and diagnosis associated with improvement in fibrosis in nonalcoholic steatohepatitis: results from the Nonalcoholic Steatohepatitis Clinical Research Network Treatment Trials. Hepatology 70(2):522\u2013531. https:\/\/doi.org\/10.1002\/hep.30418","journal-title":"Hepatology"},{"issue":"6","key":"4087_CR19","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJMoa2309000","volume":"390","author":"SA Harrison","year":"2024","unstructured":"Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, Labriola D, Moussa SE, Neff GW, Rinella ME, Anstee QM, Abdelmalek MF, Younossi Z, Baum SJ, Francque S, Charlton MR, Newsome PN, Lanthier N, Schiefke I, Mangia A, Peric\u00e0s JM, Patil R, Sanyal AJ, Noureddin M, Bansal MB, Alkhouri N, Castera L, Rudraraju M, Ratziu V, MAESTRO-NASH Investigators (2024) A phase 3, randomized, controlled trial of Resmetirom in NASH with liver fibrosis. N Engl J Med 390(6):497\u2013509. https:\/\/doi.org\/10.1056\/NEJMoa2309000","journal-title":"N Engl J Med"},{"issue":"2","key":"4087_CR20","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1111\/j.1572-0241.2006.00419.x","volume":"101","author":"KB Barker","year":"2006","unstructured":"Barker KB, Palekar NA, Bowers SP, Goldberg JE, Pulcini JP, Harrison SA (2006) Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol 101(2):368\u201373. https:\/\/doi.org\/10.1111\/j.1572-0241.2006.00419.x","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"4087_CR21","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1111\/liv.12531","volume":"35","author":"U Vespasiani-Gentilucci","year":"2015","unstructured":"Vespasiani-Gentilucci U, Carotti S, Perrone G, Mazzarelli C, Galati G, Onetti-Muda A, Picardi A, Morini S (2015) Hepatic toll-like receptor 4 expression is associated with portal inflammation and fibrosis in patients with NAFLD. Liver Int 35(2):569\u201381. https:\/\/doi.org\/10.1111\/liv.12531","journal-title":"Liver Int"},{"issue":"3","key":"4087_CR22","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.jhep.2013.04.027","volume":"59","author":"R Pais","year":"2013","unstructured":"Pais R, Charlotte F, Fedchuk L, Bedossa P, Lebray P, Poynard T, Ratziu V, LIDO Study Group (2013) A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol 59(3):550\u20136. https:\/\/doi.org\/10.1016\/j.jhep.2013.04.027","journal-title":"J Hepatol"},{"issue":"1","key":"4087_CR23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1053\/j.gastro.2007.05.012","volume":"133","author":"MM Richardson","year":"2007","unstructured":"Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhathal PS, Dixon JB, Weltman MD, Tilg H, Moschen AR, Purdie DM, Demetris AJ, Clouston AD (2007) Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction. Gastroenterology 133(1):80\u201390. https:\/\/doi.org\/10.1053\/j.gastro.2007.05.012","journal-title":"Gastroenterology"},{"issue":"9","key":"4087_CR24","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1097\/PAS.0b013e3182254283","volume":"35","author":"RM Gill","year":"2011","unstructured":"Gill RM, Belt P, Wilson L, Bass NM, Ferrell LD (2011) Centrizonal arteries and microvessels in nonalcoholic steatohepatitis. Am J Surg Pathol 35(9):1400\u20134. https:\/\/doi.org\/10.1097\/PAS.0b013e3182254283","journal-title":"Am J Surg Pathol"},{"issue":"5","key":"4087_CR25","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1002\/hep.26230","volume":"57","author":"M Swiderska-Syn","year":"2013","unstructured":"Swiderska-Syn M, Suzuki A, Guy CD, Schwimmer JB, Abdelmalek MF, Lavine JE, Diehl AM (2013) Hedgehog pathway and pediatric nonalcoholic fatty liver disease. Hepatology 57(5):1814\u201325. https:\/\/doi.org\/10.1002\/hep.26230","journal-title":"Hepatology"},{"issue":"5","key":"4087_CR26","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/j.1365-2559.2006.02416.x","volume":"49","author":"SG H\u00fcbscher","year":"2006","unstructured":"H\u00fcbscher SG (2006) Histological assessment of non-alcoholic fatty liver disease. Histopathology 49(5):450\u201365. https:\/\/doi.org\/10.1111\/j.1365-2559.2006.02416.x","journal-title":"Histopathology"},{"issue":"5","key":"4087_CR27","doi-asserted-by":"publisher","first-page":"994","DOI":"10.14309\/ajg.0000000000001072","volume":"116","author":"E Vilar-Gomez","year":"2021","unstructured":"Vilar-Gomez E, Pirola CJ, Sookoian S, Wilson LA, Belt P, Liang T, Liu W, Chalasani N (2021) Impact of the association between PNPLA3 genetic variation and dietary intake on the risk of significant fibrosis in patients with NAFLD. Am J Gastroenterol 116(5):994\u20131006. https:\/\/doi.org\/10.14309\/ajg.0000000000001072","journal-title":"Am J Gastroenterol"},{"key":"4087_CR28","doi-asserted-by":"publisher","unstructured":"Desmet VJ (2011) Ductal plates in hepatic ductular reactions. Hypothesis and implications. I. Types of ductular reaction reconsidered. Virchows Arch 458(3):251\u20139. https:\/\/doi.org\/10.1007\/s00428-011-1048-3","DOI":"10.1007\/s00428-011-1048-3"},{"key":"4087_CR29","doi-asserted-by":"publisher","unstructured":"Desmet VJ (2011) Ductal plates in hepatic ductular reactions. Hypothesis and implications. III. Implications for liver pathology. Virchows Arch 458(3):271\u20139. https:\/\/doi.org\/10.1007\/s00428-011-1050-9","DOI":"10.1007\/s00428-011-1050-9"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-025-04087-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-025-04087-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-025-04087-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T11:16:45Z","timestamp":1757157405000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-025-04087-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["4087"],"URL":"https:\/\/doi.org\/10.1007\/s00428-025-04087-5","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"8 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Behling\u2019s institution provides contract services for ICON, Covance and Sharp Healthcare Laboratories. Dr. Behling has received speaker fees from Pfizer and Alimentiv for NASH related topics.Dr. Allende has received a one-time honorarium from Mayo Clinic, Univ. of Ottawa and Educational Symposia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}]}}