Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.
Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness.
Liver Tumor Program, IRCCS de Bellis, Castellana Grotte, Italy. Electronic address: brianicarr@hotmail.com.
Brian I
BI
Carr
Liver Tumor Program, IRCCS de Bellis, Castellana Grotte, Italy.
Vito
V
Guerra
Departiment of Internal Medicine, Gastroenterology Unit, University of Genoa, Italy.
Edoardo G
EG
Giannini
Departiment of Surgical Science and Gastroenterology, Gastroenterology Unit, University of Padua, Italy.
Fabio
F
Farinati
Division of Surgery, Policlinico San Marco, Zingonia, Italy.
Francesca
F
Ciccarese
Internal Medicine and Gastroenterology Unit, Catholic University of Rome, Rome, Italy.
Gian
G
Ludovico Rapaccini
Division of Medicine, Azienda Ospedaliera Bolognini, Seriate, Italy.
Maria
M
Di Marco
Departiment of Clinical and Experimental Medicine, Medical Unit, University of Padua, Italy.
Luisa
L
Benvegnù
Department of Medical and Surgical Science, Internal Medicine Unit, Alma Mater Studiorum-University of Bologna, Italy.
Marco
M
Zoli
Department of Medicine, Internal Medicine and Hepatology Unit, Ospedale Fatebenefratelli, Milan, Italy.
Franco
F
Borzio
Gastroenterology Unit, Ospedale Belcolle, Viterbo, Italy.
Eugenio
E
Caturelli
Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy.
Maria
M
Chiaramonte
Department of Medical Surgical Sciences, Medical Semiotics Unit, Alma Mater Studiorum-University of Bologna, Italy.
Franco
F
Trevisani
D001663:Bilirubin / Q000097:blood* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D015994:Incidence; D007558:Italy; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000097:blood* / Q000378:metabolism / Q000401:mortality; D016015:Logistic Models; D016017:Odds Ratio; D010641:Phenotype; D011169:Portal Vein / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000509:alpha-Fetoproteins; D005723:gamma-Glutamyltransferase; D001663:Bilirubin