{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:09:16Z","timestamp":1790071756342,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,11,23]],"date-time":"2002-11-23T00:00:00Z","timestamp":1038009600000},"content-version":"vor","delay-in-days":295,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aims<\/jats:bold> The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and transforming growth factor\u2010\u03b2 (\u03a4GF\u2010\u03b2), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF\u2010\u03b1 and TGF\u2010\u03b2 and the severity of PBC; and (ii) the effects of UDCA therapy on TNF\u2010\u03b1 and TGF\u2010\u03b2 levels in patients with PBC.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold> We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double\u2010blind, controlled trial. Patients were divided into histological stage I\/II or stage III\/IV disease. Serum TNF\u2010\u03b1 and TGF\u2010\u03b2 levels were quantified by enzyme\u2010linked immunoabsorbent assay.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold> Baseline levels of TNF\u2010\u03b1 were significantly greater in patients with stage III\/IV compared to stage I\/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF\u2010\u03b1 levels and progression risk score compared to placebo\u2010treated patients. TNF\u2010\u03b1 and TGF\u2010\u03b2 levels were significantly reduced compared to baseline levels in the UDCA\u2010treated group after 2 years, while there was no significant change in the levels of placebo\u2010treated patients.<\/jats:p><jats:p><jats:bold>Conclusions<\/jats:bold> Serum TNF\u2010\u03b1 and TGF\u2010\u03b2 levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.<\/jats:p>","DOI":"10.1046\/j.1440-1746.2002.02672.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T05:21:39Z","timestamp":1047446499000},"page":"196-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Tumor necrosis factor\u2010<b>\u03b1<\/b> and transforming growth factor\u2010<b>\u03b2<\/b> reflect severity of liver damage in primary biliary cirrhosis"],"prefix":"10.1111","volume":"17","author":[{"given":"MANUELA","family":"NEUMAN","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PAUL","family":"ANGULO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"IZABELLA","family":"MALKIEWICZ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROBERTA","family":"JORGENSEN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NEIL","family":"SHEAR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E ROLLAND","family":"DICKSON","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JULIA","family":"HABER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GADY","family":"KATZ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KEITH","family":"LINDOR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,11,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105303242204"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90021-3"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840190512"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840220311"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365529709000190"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80216-0"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70183-5"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290301"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.pm8613058"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11293-X"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80232-9"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.35.9.1163"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840130226"},{"key":"e_1_2_6_15_2","first-page":"1","article-title":"Cytokines and inflamed liver.","volume":"23","author":"Neuman MG.","year":"1998","journal-title":"Clin. 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