{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:10:22Z","timestamp":1743379822814,"version":"3.40.3"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2009,2,25]],"date-time":"2009-02-25T00:00:00Z","timestamp":1235520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Addenbrooke's Hospital Hepatology Endowment Fund"},{"name":"Frank Litchfield Charitable Trust"},{"name":"British Transplant Society"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Hepatitis C virus (HCV) is a leading indication for liver transplantation worldwide, but graft infection with HCV frequently leads to hepatic fibrosis. Acute cellular rejection (ACR) can be difficult to distinguish confidently from HCV, even with histology, but accurate diagnosis is critical because treatment of ACR may accelerate HCV-related graft injury. Immunohistochemistry was undertaken on 99 liver biopsies from 31 patients with HCV graft infection, 22 patients with ACR, and 11 patients with HCV infection and unexplained graft dysfunction to investigate whether lymphocyte expression of minichromosome maintenance protein-2 (Mcm-2), a marker of licensed cell cycle entry, assessed in a novel semiautomated system could distinguish between ACR and graft infection with HCV. The portal tract area was greater in ACR than in HCV graft infection (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.027), but there was considerable overlap. However, both the number of Mcm-2\u2013positive lymphocytes per portal tract and the number of Mcm-2\u2013positive lymphocytes per millimeter squared of portal tract distinguished between ACR and HCV graft infection (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0001). A cutoff value of 107 positive cells per portal tract had a sensitivity of 81.8% and a specificity of 91.9% (positive predictive value of 66.67% and negative predictive value of 95.75%). Of 11 HCV-infected patients with an uncertain diagnosis, 7 were deemed ultimately to have HCV graft infection, and 4 had superimposed corticosteroid-responsive ACR. The number of Mcm-2\u2013positive cells per portal tract and per millimeter squared of portal tract again distinguished clearly between the groups (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.012). In conclusion, lymphocyte Mcm-2 expression is a useful adjunct to histology in differentiating between HCV graft infection and ACR. Patients with a low number of Mcm-2\u2013positive portal tract lymphocytes are less likely to have ACR.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/lt.21680","type":"journal-article","created":{"date-parts":[[2009,2,25]],"date-time":"2009-02-25T20:05:39Z","timestamp":1235592339000},"page":"306-312","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Minichromosome maintenance protein-2\u2013positive portal tract lymphocytes distinguish acute cellular rejection from hepatitis C virus recurrence after liver transplantation"],"prefix":"10.1097","volume":"15","author":[{"given":"Esther","family":"Unitt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Gelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme J. M.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-7-20250330","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1053\/jlts.2002.35855","article-title":"Hepatitis C: magnitude of the problem.","volume":"8","author":"Rakela","year":"2002","journal-title":"Liver Transpl"},{"key":"R2-7-20250330","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1053\/gast.1997.v112.agast970575","article-title":"Hepatitis C after orthotopic liver transplantation.","volume":"112","author":"Araya","year":"1997","journal-title":"Gastroenterology"},{"key":"R3-7-20250330","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJM199603283341302","article-title":"Longterm outcome of hepatitis C infection after liver transplantation.","volume":"334","author":"Gane","year":"1996","journal-title":"N Engl J Med"},{"key":"R4-7-20250330","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1016\/j.transproceed.2006.08.056","article-title":"Morbidity and mortality in liver retransplantation.","volume":"38","author":"Alamo","year":"2006","journal-title":"Transplant Proc"},{"key":"R5-7-20250330","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.transproceed.2005.03.081","article-title":"Repeated steroid pulse therapies in HCVpositive liver recipients: significant risk factor for HCVrelated graft loss.","volume":"37","author":"Bahra","year":"2005","journal-title":"Transplant Proc"},{"key":"R6-7-20250330","first-page":"1453","article-title":"Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation.","volume":"92","author":"Rosen","year":"1997","journal-title":"Am J Gastroenterol"},{"key":"R7-7-20250330","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s10595-002-2537-5","article-title":"The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation.","volume":"33","author":"Sugo","year":"2003","journal-title":"Surg Today"},{"key":"R8-7-20250330","first-page":"S107","article-title":"Impact of immunosuppression and acute rejection on recurrence of hepatitis C: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.","volume":"5","author":"Charlton","year":"1999","journal-title":"Liver Transpl Surg"},{"key":"R9-7-20250330","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/hep.510250328","article-title":"Banff schema for grading liver allograft rejection: an international consensus document.","volume":"25","year":"1997","journal-title":"Hepatology"},{"key":"R10-7-20250330","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/lt.20245","article-title":"Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation.","volume":"10","author":"Regev","year":"2004","journal-title":"Liver Transpl"},{"key":"R11-7-20250330","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1399-0012.2004.00310.x","article-title":"Lobular damage caused by cellular and humoral immunity in liver allograft rejection.","volume":"19","author":"Sawada","year":"2005","journal-title":"Clin Transplant"},{"key":"R12-7-20250330","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/00000478-200606000-00008","article-title":"Endothelitis in chronic viral hepatitis: a comparison with acute cellular rejection and nonalcoholic steatohepatitis.","volume":"30","author":"Yeh","year":"2006","journal-title":"Am J Surg Pathol"},{"key":"R13-7-20250330","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s005350170083","article-title":"Clinical, virological, and pathological significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C.","volume":"36","author":"Hwang","year":"2001","journal-title":"J Gastroenterol"},{"key":"R14-7-20250330","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0016-5085(92)91129-R","article-title":"Recurrent and acquired hepatitis C viral infection in liver transplant recipients.","volume":"103","author":"Wright","year":"1992","journal-title":"Gastroenterology"},{"key":"R15-7-20250330","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1097\/00007890-199511270-00007","article-title":"Timing, significance, and prognosis of late acute liver allograft rejection.","volume":"60","author":"Anand","year":"1995","journal-title":"Transplantation"},{"key":"R16-7-20250330","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/hep.1840210107","article-title":"Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation.","volume":"21","author":"Sheiner","year":"1995","journal-title":"Hepatology"},{"key":"R17-7-20250330","first-page":"145","article-title":"Hepatitis C in liver allografts.","volume":"117","author":"Thung","year":"1993","journal-title":"Arch Pathol Lab Med"},{"key":"R18-7-20250330","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1600-6143.2005.01180.x","article-title":"C4d in acute rejection after liver transplantationa valuable tool in differential diagnosis to hepatitis C recurrence.","volume":"6","author":"Schmeding","year":"2006","journal-title":"Am J Transplant"},{"key":"R19-7-20250330","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1053\/jlts.2001.23909","article-title":"The use of hepatitis C viral RNA levels in liver tissue to distinguish rejection from recurrent hepatitis C.","volume":"7","author":"Gottschlich","year":"2001","journal-title":"Liver Transpl"},{"key":"R20-7-20250330","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1517\/14712598.7.11.1689","article-title":"Tregulatory lymphocytes and chronic viral hepatitis.","volume":"7","author":"Rushbrook","year":"2007","journal-title":"Expert Opin Biol Ther"},{"key":"R21-7-20250330","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jhep.2007.03.023","article-title":"Quantification and localisation of FOXP3 T lymphocytes and relation to hepatic inflammation during chronic HCV infection.","volume":"47","author":"Ward","year":"2007","journal-title":"J Hepatol"},{"key":"R22-7-20250330","doi-asserted-by":"crossref","first-page":"7852","DOI":"10.1128\/JVI.79.12.7852-7859.2005","article-title":"Regulatory T cells suppress in vitro proliferation of virusspecific CD8 T cells during persistent hepatitis C virus infection.","volume":"79","author":"Rushbrook","year":"2005","journal-title":"J Virol"},{"key":"R23-7-20250330","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1053\/j.gastro.2004.09.076","article-title":"Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection.","volume":"128","author":"Marshall","year":"2005","journal-title":"Gastroenterology"},{"key":"R24-7-20250330","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/lt.20347","article-title":"Hepatocyte expression of minichromosome maintenance protein2 predicts fibrosis progression after transplantation for chronic hepatitis C virus: a pilot study.","volume":"11","author":"Marshall","year":"2005","journal-title":"Liver Transpl"},{"key":"R25-7-20250330","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/hep.20644","article-title":"Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of Tregulatory cells.","volume":"41","author":"Unitt","year":"2005","journal-title":"Hepatology"},{"key":"R26-7-20250330","first-page":"2121","article-title":"Minichromosome maintenance proteins as biological markers of dysplasia and malignancy.","volume":"5","author":"Freeman","year":"1999","journal-title":"Clin Cancer Res"},{"key":"R27-7-20250330","first-page":"1075","article-title":"Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility.","volume":"8","author":"Rodins","year":"2002","journal-title":"Clin Cancer Res"}],"container-title":["Liver Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.21680","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.21680","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01445473-200903000-00007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T23:38:40Z","timestamp":1743377920000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01445473-200903000-00007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009]]}},"URL":"https:\/\/doi.org\/10.1002\/lt.21680","relation":{},"ISSN":["1527-6465"],"issn-type":[{"type":"print","value":"1527-6465"}],"subject":[],"published":{"date-parts":[[2009,3]]}}}