Alpha-fetoprotein and p53 autoantibodies in patients with chronic hepatitis C.
Hepatitis C virus infection is a common cause of chronic liver disease and hepatocellular carcinoma. Recently, mutations in the p53 tumor suppressor gene with generation of circulating autoantibodies to p53 protein have been detected in a significant proportion of patients with different malignancies. Using ELISA methods we assessed alpha-fetoprotein and anti-p53 as serological screening parameters for hepatocellular carcinoma in 147 consecutive patients with chronic hepatitis C. Liver cirrhosis was histologically diagnosed in 58 patients (39.5%) and a hepatocellular carcinoma confirmed in seven patients (4.8%). Serum alpha-fetoprotein was raised above 20 ng/ml in 26/147 patients and above 100 ng/ml in 5/147 patients. In 6/7 patients with hepatocellular carcinoma, alpha-fetoprotein was raised above 20 ng/ml, but only in 3/7 cases above 100 ng/ml, resulting in a sensitivity and specificity of 85.7% and 85.7% (alpha-fetoprotein > 20 ng/ml) and 42.9% and 98.6% (alpha-fetoprotein > 100 ng/ml) for the detection of hepatocellular carcinoma, respectively. Autoantibodies to p53 were detected in 3/7 patients with hepatocellular carcinoma, but in 0/140 patients without malignancy (sensitivity 42.9%, specificity 100%). Screening for hepatocellular carcinoma was improved by combining alpha-fetoprotein measurement (level > 100 ng/ml) with detection for anti-p53 (sensitivity 71.4%, specificity 98.6%). In conclusion, the presence of anti-p53 was highly specific for malignancy and independent of alpha-fetoprotein status. Further studies including a larger number of patients with hepatitis C virus-related hepatocellular carcinoma are required to investigate whether serological testing for anti-p53 in combination with alpha-fetoprotein might improve the detection of hepatocellular carcinoma in high-risk patients with liver cirrhosis.
Second Department of Medicine, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
J
J
Raedle
W K
WK
Roth
G
G
Oremek
W F
WF
Caspary
S
S
Zeuzem
D001323:Autoantibodies / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006526:Hepatitis C / Q000150:complications*; D006521:Hepatitis, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000821:virology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology*; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*; D000509:alpha-Fetoproteins / Q000032:analysis*
D001323:Autoantibodies; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins