Serum chromogranin-A in hepatocellular carcinoma: Diagnostic utility and limits

AIM: The utility of serum alpha-fetoprotein (α-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±1046), in LC (249±369), in CH (87±94), in CRF (1390±1401), 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 (250-1289 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 a-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 a-FP and CgA in patients with HCC and in patients with cirrhosis. CONCLUSION: When HCC is suspected and a-FP is normal or <200 ng/mL, CgA serum values represent a complementary diagnostic tool, unless kidney or heart failure is present.

Impact of intrarectal chromofungin treatment on dendritic cellsrelated markers in different immune compartments in colonic inflammatory conditions

BACKGROUND Chromofungin(CHR:chromogranin-A 47-66)is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties.Ulcerative colitis(UC)is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c+cells.AIM To investigate the association between CHR treatment and dendritic cells(DCs)-related markers in different immune compartments in colitis.METHODS A model of acute UC-like colitis using dextran sulphate sodium(DSS)was used in addition to biopsies collected from UC patients.RESULTS Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c,CD40,CD80,CD86 and interleukin(IL)-12p40 in the inflamed colonic mucosa and CD11c,CD80,CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen.Furthermore,CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+cells and decreased NF-κB expression in the colon and of splenic CD11c+cells.In vitro,CHR decreased CD40,CD80,CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c+DCs stimulated with lipopolysaccharide.Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway.In patients with active UC,CHR level was reduced and showed a negative linear relationship with CD11c and CD86.CONCLUSION CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c+cells.CHR could be a potential therapy of UC.