Reactivity to B Cell Epitopes within Hepatitis C Virus Core Protein and Hepatocellular Carcinoma

Our aim was to investigate the existence of an association between B cell responsiveness to hepatitis C virus (HCV) core protein and progression of liver disease. In fact, the persistence of HCV infection is permitted by avoidance of viral clearance, despite chronic inflammation in the liver; this process ends with the development of hepatocellular carcinoma in many patients. On the basis of computerized prediction of antigenicity of the genomic sequence of HCV core protein, three 15-mer peptides (named Q15V, R15P, and G15V) were synthesized to be used as antigens in an enzyme immunoassay. Sera from 97 patients (65 males and 32 females) were tested: 43 patients had mild chronic liver disease (steatofibrosis, chronic persistent, or chronic active hepatitis) and 54 had cirrhosis, which was complicated by hepatocellular carcinoma (HCC) in 19. Seventy-six patients were positive to anti-HCV testing by second generation ELISA and 21 were negative. Rates of positivity for synthetic peptides in anti-HCV-positive versus anti-HCV negative patients were as follows: 53 of 76 and 0 of 21 for anti-Q15V; 41 of 76 and 0 of 21 for R15P; and 67 of 76 and 2 of 21 for G15V. Rates of positivity to anti-Q15V and anti-G15V were similar among diagnostic groups (Pearson's χ², 1.97, P > 0.10 and 0.45, P > 0.10), whereas anti-R15P antibodies were detected at a significantly lower rate in patients with HCC (2/13) in comparison to mild chronic liver disease (22/35) and cirrhosis (17/28) (Pearson's χ², 9.42, P <0.01). We conclude that anti-R15P antibodies are uncommon in anti-HCV-positive patients with HCC. During the course of chronic HCV infection, anti-R15P testing might help to identify a subgroup at higher risk to develop HCC.