Serum chromogranin-A in hepatocellular carcinoma: diagnostic utility and limits
Aldo Spadaro1, Antonino Ajello, Carmela Morace
1Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Università di Messisna, 98125 Messina, Italy. aldo.spadaro@unime.it
Insights
Serum chromogranin-A (CgA) shows promise as a biomarker for detecting hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). CgA offers complementary diagnostic value when alpha-fetoprotein (alpha-FP) levels are inconclusive.
Area of Science:
- Hepatology
- Oncology
- Biomarker Discovery
Background:
- Serum alpha-fetoprotein (alpha-FP) has limited utility for hepatocellular carcinoma (HCC) detection.
- Elevated serum chromogranin-A (CgA) has been observed in HCC.
- Hepatic, renal, and cardiac functions can affect circulating CgA levels.
Purpose of the Study:
- To evaluate the sensitivity and specificity of serum CgA for detecting HCC in patients with liver cirrhosis (LC).
Main Methods:
- Serum CgA levels were measured using radioimmunoassay (RIA) in 339 patients, including HCC, LC, chronic hepatitis (CH), and various disease controls.
- Statistical analyses included Pearson correlation, non-parametric combination tests, and confidence interval analysis.
- Exclusion criteria involved patients with liver disease or IBD and concomitant renal and/or heart failure.
Main Results:
- Serum CgA levels above 100 ng/mL were detected in 83% of HCC patients, 48% of LC patients, and 100% of chronic heart failure (CHF) patients.
- Mean CgA values were significantly higher in HCC, LC, CH, chronic renal failure (CRF), CHF, and inflammatory bowel disease (IBD) groups compared to healthy controls.
- For HCC detection in patients with cirrhosis, CgA demonstrated a sensitivity of 61% and specificity of 82%.
- Serum alpha-FP was elevated (>200 ng/mL) in only 21% of HCC patients and none of the LC patients.
Conclusions:
- Serum CgA can serve as a complementary diagnostic tool for suspected HCC when alpha-fetoprotein (alpha-FP) levels are normal or low (<200 ng/mL).
- The utility of CgA as a biomarker is limited in the presence of kidney or heart failure.
Aim:
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.
Conclusion:
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.