{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T10:47:15Z","timestamp":1783248435848,"version":"3.54.6"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":942,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Liver biopsy is important for diagnosing primary biliary cirrhosis (PBC). Prior investigations suggest that immunostaining for biliary keratin 19 (K19) may show the earliest changes suspicious for PBC, namely, loss of the canals of Hering (CoH). We aimed to study the clinical outcomes of patients whose biopsy specimens appeared histologically near normal or with minimal inflammatory changes, but in which K19 staining revealed widespread periportal CoH loss, a finding we termed \u201cminimal change PBC.\u201d Ten patients were identified prospectively as having nearly normal or mildly inflamed biopsy specimens without diagnostic or suggestive histologic features of PBC, but with near complete CoH loss; six had available follow-up clinical data, one had follow-up biopsy. Controls for clinical and\/or K19 analysis included six normal livers and biopsy specimens from 10 patients with confirmed early PBC, 10 with early stage chronic hepatitis C (CHC), and nine with resolving, self-limited hepatitis (RSLH). Staining for K19 in normal controls, livers with \u201cminimal change\u201d PBC, CHC, and RSLH showed 9.2 \u00b1 6.0, 0.44 \u00b1 0.37 (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.0001), 5.7 \u00b1 4.6 (n.s.), 4.1 \u00b1 2.1 (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.02) CoH per portal tract, respectively. Patients with available clinical follow up, compared to patients with diagnostic early-stage PBC biopsies, showed identical treatment responses to ursodeoxycholic acid, similar rates and types of nonhepatic autoimmune diseases, and\/or subsequent development of autoimmune hepatitis overlap syndrome.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>\n                                 <jats:bold>We suggest that CoH loss demonstrated by K19 immunostaining is an early feature in PBC. Clinical findings in the years following biopsy, including response to ursodeoxycholic acid, show identical changes to patients with biopsy confirmed PBC. We suggest that this \u201cminimal change\u201d feature may support a clinical diagnosis of PBC even in the absence of characteristic, granulomatous, duct destructive lesions.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26020","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T08:27:33Z","timestamp":1345624053000},"page":"700-707","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":38,"title":["Keratin 19 Demonstration of Canal of Hering Loss in Primary Biliary Cirrhosis: \u201cMinimal Change PBC\u201d?"],"prefix":"10.1097","volume":"57","author":[{"given":"Fahad M.","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arathi Rajendra","family":"Komarla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo G.","family":"Mendoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry C.","family":"Bodenheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil D.","family":"Theise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-29-20241201","doi-asserted-by":"crossref","first-page":"321326","DOI":"10.1055\/s-2005-916323","article-title":"The natural history of PBC: has it changed?","volume":"25","author":"Lee","year":"2005","journal-title":"Semin Liver Dis"},{"key":"R2-29-20241201","doi-asserted-by":"crossref","first-page":"745758","DOI":"10.1016\/j.jhep.2009.11.027","article-title":"Primary biliary cirrhosis: a 2010 update.","volume":"52","author":"Poupon","year":"2010","journal-title":"J Hepatol"},{"key":"R3-29-20241201","first-page":"291308","article-title":"; American Association for Study of Liver Diseases. Primary biliary cirrhosis.","volume":"50","author":"Lindor","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R4-29-20241201","doi-asserted-by":"crossref","first-page":"983988","DOI":"10.1053\/hupa.2002.128060","article-title":"Destruction of canals of Hering in primary biliary cirrhosis.","volume":"33","author":"Saxena","year":"2002","journal-title":"Hum Pathol"},{"key":"R5-29-20241201","doi-asserted-by":"crossref","first-page":"14251433","DOI":"10.1002\/hep.510300614","article-title":"The canals of hering and hepatic stem cells in humans.","volume":"30","author":"Theise","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R6-29-20241201","first-page":"4348","article-title":"Canals of Hering: recent insights and current knowledge.","volume":"24","author":"Saxena","year":"2004","journal-title":"Semin Liver Dis"},{"key":"R7-29-20241201","doi-asserted-by":"crossref","first-page":"15981607","DOI":"10.1002\/hep.22516","article-title":"The stem cell niche of human livers: symmetry between regeneration and development.","volume":"48","author":"Zhang","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R8-29-20241201","doi-asserted-by":"crossref","first-page":"323331","DOI":"10.1002\/hep.510280206","article-title":"The normal adult human liver biopsy: a quantitative reference standard.","volume":"28","author":"Crawford","year":"1998","journal-title":"HEPATOLOGY"},{"key":"R10-29-20241201","doi-asserted-by":"crossref","first-page":"210225","DOI":"10.1034\/j.1600-0528.2002.017402.x","article-title":"Primary biliary cirrhosis: an orchestrated immune response against epithelial cells.","volume":"174","author":"Gershwin","year":"2000","journal-title":"Immunol Rev"},{"key":"R11-29-20241201","doi-asserted-by":"crossref","first-page":"182187","DOI":"10.1016\/j.hepres.2006.07.014","article-title":"Cytokeratin7, cytokeratin19, and cKit: Immunoreaction during the evolution stages of primary biliary cirrhosis.","volume":"36","author":"Chatzipantelis","year":"2006","journal-title":"Hepatol Res"},{"key":"R12-29-20241201","doi-asserted-by":"crossref","first-page":"935938","DOI":"10.1136\/gut.36.6.935","article-title":"Characterisation of patients with a complete biochemical response to ursodeoxycholic acid.","volume":"36","author":"Jorgensen","year":"1995","journal-title":"Gut"},{"key":"R13-29-20241201","doi-asserted-by":"crossref","first-page":"12321242","DOI":"10.1007\/BF02065530","article-title":"Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases.","volume":"40","author":"Goodman","year":"1995","journal-title":"Dig Dis Sci"},{"key":"R14-29-20241201","doi-asserted-by":"crossref","first-page":"659665","DOI":"10.1002\/hep.21583","article-title":"A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMAnegative primary biliary cirrhosis.","volume":"45","author":"Oertelt","year":"2007","journal-title":"HEPATOLOGY"},{"key":"RU15-29-20241201","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1046\/j.1365-2036.2003.01381.x","article-title":"Review article: is there an optimal therapeutic regimen for antimithochondrial antibodynegative primary biliary cirrhosis (autoimmune cholangitis)?","volume":"17","author":"Gisbert","year":"2003","journal-title":"Aliment Pharmacol Ther"},{"key":"RU16-29-20241201","doi-asserted-by":"crossref","first-page":"243248","DOI":"10.1053\/jhep.2001.26514","article-title":"Detection of antimitochondrial autoantibodies in immunofluorescent AMAnegative patients with primary biliary cirrhosis using recombinant autoantigens.","volume":"34","author":"Miyakawa","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R17-29-20241201","doi-asserted-by":"crossref","first-page":"8590","DOI":"10.1002\/hep.21229","article-title":"Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis.","volume":"44","author":"Poupon","year":"2006","journal-title":"HEPATOLOGY"},{"key":"R18-29-20241201","doi-asserted-by":"crossref","first-page":"971975","DOI":"10.1007\/BF01311724","article-title":"Increased incidence of hypothyroidism in primary biliary cirrhosis.","volume":"28","author":"Elta","year":"1983","journal-title":"Dig Dis Sci"},{"key":"R19-29-20241201","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.2188\/jea.16.30","article-title":"Antimitochondrial antibody negative primary biliary cirrhosis in Japan: utilization of clinical data when patients applied to receive public financial aid.","volume":"16","author":"Sakauchi","year":"2006","journal-title":"J Epidemiol"},{"key":"R20-29-20241201","doi-asserted-by":"crossref","first-page":"19942002","DOI":"10.1002\/hep.22218","article-title":"The hepatic stem cell niche: identification by label retaining cell assay.","volume":"47","author":"Kuwahara","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R21-29-20241201","doi-asserted-by":"crossref","first-page":"964973","DOI":"10.1002\/hep.24122","article-title":"Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stemprogenitor cells in humans.","volume":"53","author":"Yoon","year":"2011","journal-title":"HEPATOLOGY"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26020","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201302000-00029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T14:05:42Z","timestamp":1733061942000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201302000-00029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.26020","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2013,2]]}}}