title: Plasma osteopontin is a biomarker for the severity of alcoholic liver cirrhosis, not for hepatocellular carcinoma screening.
abstract: BACKGROUND
  Implementation of surveillance programs for at-risk populations and identification of biomarkers for early hepatocellular carcinoma (HCC) detection are a major public health goal. Recently, osteopontin (OPN) has attracted attention as a promising biomarker, with some potential advantages compared to alpha-fetoprotein (AFP), but its role in the context of alcoholic cirrhosis has never been assessed. The aims of this study are to assess the utility of plasma OPN in the diagnosis of HCC in alcoholic cirrhotic patients and to investigate whether increased values are due to the tumor or underlying liver disease severity.
  
  
  METHODS
  A total of 90 consecutively alcoholic cirrhosis patients, observed between Jun 2013 and May 2014 at a Liver Disease Unit, were included and divided into two groups: 45 without (group I) and 45 with HCC (group II). Plasma levels of OPN (ELISA, Immuno-Biological Laboratories, Gunma, Japan) and AFP (IMMULITE® 2000 AFP, Siemens Healthcare Diagnostics, Tarrytown, New York) were assessed. The diagnostic accuracy of each marker was evaluated using Receiver-Operating Characteristic (ROC) curve analysis (AUC) and its 95 % Confidence Interval (CI).
  
  
  RESULTS
  Plasma OPN levels in group I patients (1176.28 +/-744.59 ng/mL) weren't significantly different from those of group II (1210.75 +/-800.60 ng/mL) (p = 0.826). OPN levels significantly increased with advancing BCLC tumor stage and with advancing Child-Pugh class, in both groups. Comparing the two groups, AUC for OPN and AFP were 0.51 (95 % CI: 0.39-0.63) and 0.79 (95 % CI: 0.70-0.89), respectively. Based on the ROC analysis, there were no satisfactory cut-off values for OPN that would distinguish patients with from those without tumour.
  
  
  CONCLUSIONS
  Despite having a correlation with BCLC stage, the same was observed with progressive deterioration of underlying liver function in terms of Child-Pugh class and MELD score, and isn't a useful diagnostic biomarker for HCC in alcoholic cirrhotic patients, particularly in the early stages. AFP confirms the performance evidenced in other studies, being superior to OPN. Searching more specific biomarkers for early diagnosis of HCC in alcoholic cirrhosis is still warranted.
authors.affiliation: Internal Medicine A-Centro Hospitalar e Universitário de Coimbra, Portugal, and University of Coimbra, Faculty of Medicine, Coimbra, Portugal, Av. Bissaya Barreto e Praceta Mota Pinto, 3000-075, Coimbra, Portugal. adeliasimao@gmail.com.
authors.forename: Adélia
authors.initials: A
authors.lastname: Simão
authors.affiliation: Internal Medicine A-Centro Hospitalar e Universitário de Coimbra, Portugal, and University of Coimbra, Faculty of Medicine, Coimbra, Portugal, Av. Bissaya Barreto e Praceta Mota Pinto, 3000-075, Coimbra, Portugal. joaocarvalhomadaleno@gmail.com.
authors.forename: João
authors.initials: J
authors.lastname: Madaleno
authors.affiliation: Internal Medicine A-Centro Hospitalar e Universitário de Coimbra, Portugal, and University of Coimbra, Faculty of Medicine, Coimbra, Portugal, Av. Bissaya Barreto e Praceta Mota Pinto, 3000-075, Coimbra, Portugal. silvanunojose@gmail.com.
authors.forename: Nuno
authors.initials: N
authors.lastname: Silva
authors.affiliation: Clinical Pathology-Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. fernandomrodrigues@huc.min-saude.pt.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues
authors.affiliation: Clinical Pathology-Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. caseirop@gmail.com.
authors.forename: Paula
authors.initials: P
authors.lastname: Caseiro
authors.affiliation: Internal Medicine A-Centro Hospitalar e Universitário de Coimbra, Portugal, and University of Coimbra, Faculty of Medicine, Coimbra, Portugal, Av. Bissaya Barreto e Praceta Mota Pinto, 3000-075, Coimbra, Portugal. jmncosta@gmail.com.
authors.forename: José Nascimento
authors.initials: JN
authors.lastname: Costa
authors.affiliation: Internal Medicine A-Centro Hospitalar e Universitário de Coimbra, Portugal, and University of Coimbra, Faculty of Medicine, Coimbra, Portugal, Av. Bissaya Barreto e Praceta Mota Pinto, 3000-075, Coimbra, Portugal. acarvalho@fmed.uc.pt.
authors.forename: Armando
authors.initials: A
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D012372:ROC Curve; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D053495:Osteopontin