Hepatitis C virus (HCV) possesses a second open reading frame (ORF)
within the core gene encoding an additional protein, known as the
alternative reading frame protein (ARFP), F or core+1. The biological
significance of the core+1/ARF protein remains elusive. However, several
independent studies have shown the presence of core+1/ARFP antibodies in
chronically HCV-infected patients. Furthermore, a higher prevalence of
core+1/ARFP antibodies was detected in patients with HCV-associated
hepatocellular carcinoma (HCC). Here, we investigated the incidence of
core+1/ARFPantibodies in chronically HCV-infected patients at different
stages of cirrhosis in comparison to chronically HCV-infected patients
at earlier stages of disease. Using ELISA, we assessed the prevalence of
anti-core+1 antibodies in 30 patients with advanced cirrhosis [model
for end-stage liver disease (MELD) >= 15] in comparison with 50 patients
with mild cirrhosis (MELD <15) and 164 chronic HCV patients without
cirrhosis. 28.7 % of HCV patients with cirrhosis were positive for
anti-core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV
patients. Moreover, there was significantly higher positivity for
anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %)
compared to those with early cirrhosis (24%) (P<0.05). These findings,
together with the high prevalence of anti-core+1 antibodies in HCV
patients with HCC, suggest that core+1 protein may have a role in
virus-associated pathogenesis, and provide evidence to suggest that the
levels of anti-core+1 antibodies may serve as a marker for disease
progression
