{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:17:14Z","timestamp":1788200234826,"version":"build-2803163510"},"reference-count":27,"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":5509,"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":[[2000,8]]},"abstract":"<jats:sec><jats:title\/><jats:p>Clinical course in hepatocellular carcinoma may be very different. We prospectively evaluated 96 patients with hepatocellular carcinoma unsuitable for radical therapy to investigate factors that could influence survival. Clinical, pathologic, and molecular data of patients were analyzed by univariate and multivariate analysis. The overall actuarial probability of survival at year 1, 2, 3, 4, 5, and 6 was 72%, 41%, 38%, 24%, 20%, and 9%. At univariate analysis, alpha-fetoprotein (AFP) (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0082); alkaline phosphatase (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0281); bilirubin (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0076); etiology (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0001); increment of tumor mass at month 3 (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0051); type of estrogen receptor (ER) in the tumor (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0000); prothrombin time (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0003); and portal vein thrombosis (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0000) had prognostic significance. At multivariate analysis, only type of ER (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0000) and bilirubin (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0030) showed independent predictive value for mortality. Survival was significantly longer in patients with wild-type estrogen receptors (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0000). Cumulative probability of survival at year 1, 2, 3, 4, 5, and 6 was 94%, 66%, 52%, 43%, 35%, and 18% for wild-type and 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients alive after 4 years). Hepatitis B surface antigen (HBsAg)-positive patients with variant ERs had a median survival of 8 months versus 45 months in anti-hepatitis C virus-positive patients with wild-type ERs (<jats:italic toggle=\"yes\">P<\/jats:italic>= .0001). In conclusion, (1) the presence of variant liver ER transcripts in the tumor was the strongest negative predictor of survival in inoperable hepatocellular carcinoma; (2) their presence was associated with spontaneous survival significantly worse than in patients with wild-type estrogen receptors; and (3) HBsAg-positive patients with variant receptors were characterized by the worst survival.<\/jats:p><\/jats:sec>","DOI":"10.1053\/jhep.2000.9603","type":"journal-article","created":{"date-parts":[[2004,3,19]],"date-time":"2004-03-19T22:03:01Z","timestamp":1079733781000},"page":"233-238","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":180,"title":["Natural history of inoperable hepatocellular carcinoma: Estrogen receptors\u2019 status in the tumor is the strongest prognostic factor for 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