Alpha-fetoprotein Synthesis in Human Hepatocellular Carcinoma: Correlation with Hepatitis B Surface Antigen Expression

Abstract

We analyzed the pattern of alpha-fetoprotein (AFP) synthesis in 40 consecutive human hepatocarcinomas (HCC) in relation to hepatitis B viral (HBV) infection. In addition, histopathological characteristics of liver parenchyma and the tumor itself were examined. Elevated AFP (>20 nglml) were found in 90% of HCC patients and in none of the controls. In 35% of HCC cases, serum AFP was above 100,000 nglml. AFP levels were significantly higher in patients seropositive for hepatitis B surface antigen (HBsAg) compared with their negative counterparts (mean log[AFP]: 4.28 ± 1.67 vs. 3.28 ± 1.96, respectively; geometric mean (GM): 19,322.6 nglml and 1939.5 nglml, respectively; p < 0.05). Furthermore, serum AFP levels were higher in HCC patients with liver cirrhosis than in those without (log[AFP] :4.43 ± 1.58 vs. 3.23 ± 1.98, respectively; p < 0.05). However, the relationship of cirrhosis with AFP was confounded by the high prevalence ofHBsAg in cirrhotic HCC patients. There was no correlation of AFP with either liver necrosis (abnormal AFP in 45% of cases; mean log[AFP]: 3.99 ± 1.91 vs. 3.75 ± 1.85 forHCC0 with and without necrosis, respectively; 0.05 < p < 0.68, not significant (NS)), or inflammation (abnormal AFP in 25%; mean log[AFP]: 4.33 ± 1.62 vs. 3.70 ± 1.93 for HCC with and without inflammation, respectively; 0.05 < p < 0.39, NS). A vast majority of HCC (75%) were moderately (grade 2–3) or poorly differentiated tumors (grade 3, grade 4, or combined grade 3–4). Serum AFP did not correlate with tumor grade. Immunohistochemical analysis ofHBsAg and AFP confirmed the serological findings, and confirmed earlier observations of elevated AFP in HBsAg-positive patients. These results may reflect pathogenic and biological differences between HBsAG-secreting and nonsecreting HCC.