title: Serum chromogranin-A in hepatocellular carcinoma: diagnostic utility and limits.
abstract: OBJECTIVE
  The utility of serum alpha-fetoprotein (alpha-FP) for the detection of hepatocellular carcinoma (HCC) is questionable. High serum levels of chromogranin-A (CgA) have recently been reported in HCC. Impaired hepatic, renal, and heart functions influence circulating CgA. The aim of this study was to assess sensitivity and specificity of serum CgA as a marker of HCC in patients with liver cirrhosis (LC).
  
  
  METHODS
  Serum CgA levels were measured by RIA in 339 patients of which 54 HCC, 132 LC, 45 chronic hepatitis (CH), 27 chronic heart failure (CHF), 36 chronic renal failure (CRF), 45 chronic inflammatory bowel disease (IBD) as disease controls and in 75 healthy controls. Patients with liver disease or IBD and concomitant renal and/or heart failure were excluded. Pearson correlation, non-parametric combination test and confidence interval analysis were used for statistical analysis.
  
  
  RESULTS
  Serum CgA above normal values (100 ng/mL) were found in 83% of HCC patients, in 48% of LC patients, in 20% of CH patients, in 33% of IBD patients, in 92% of CRF patients, in 100% of CHF patients, and in none of the healthy controls. The mean CgA values in HCC (769+/-1 046), in LC (249+/-369), in CH (87+/-94), in CRF (1,390+/-1,401), in CHF (577+/-539), in IBD (146+/-287) were significantly higher than those in healthy controls (48+/-18). HCC patients had higher CgA values (P<0.01) than LC, CH, and IBD patients but did not differ from those with CRF or CHF. The 95% CI for the mean (250-1 289 ng/mL) in HCC patients was selected as a CgA range and the lower value of such range was assumed as cut-off. Sensitivity and specificity of CgA, calculated in relation to the cut-off in patients with cirrhosis and HCC, were respectively 61% (CI 48-73%) and 82% (CI 75-88%). Serum alpha-FP values were >200 ng/mL in 21% of the HCC patients and in none of the LC patients. No significant correlation was found between alpha-FP and CgA in patients with HCC and in patients with cirrhosis.
  
  
  CONCLUSIONS
  When HCC is suspected and alpha-FP is normal or <200 ng/mL, CgA serum values represent a complementary diagnostic tool, unless kidney or heart failure is present.
authors.affiliation: Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Università di Messisna, 98125 Messina, Italy. aldo.spadaro@unime.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Spadaro
authors.forename: Antonino
authors.initials: A
authors.lastname: Ajello
authors.forename: Carmela
authors.initials: C
authors.lastname: Morace
authors.forename: Agata
authors.initials: A
authors.lastname: Zirilli
authors.forename: Graziella
authors.initials: G
authors.lastname: D'arrigo
authors.forename: Carmelo
authors.initials: C
authors.lastname: Luigiano
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.forename: Anna
authors.initials: A
authors.lastname: Bene
authors.forename: Domenico
authors.initials: D
authors.lastname: Migliorato
authors.forename: Santi
authors.initials: S
authors.lastname: Turiano
authors.forename: Oscar
authors.initials: O
authors.lastname: Ferraù
authors.forename: Maria-Antonietta
authors.initials: MA
authors.lastname: Freni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis*; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood*; D005260:Female; D006521:Hepatitis, Chronic / Q000097:blood / Q000175:diagnosis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins