Nuclear factor-kappa B in the liver of patients with chronic hepatitis C: Decreased RelA expression is associated with enhanced fibrosis progression

The mechanisms of liver damage in chronic hepatitis C virus (HCV) infection are poorly understood. The transcription factor, nuclear factor-kappaB (NF -kappaB), regulates the expression of genes involved in apoptosis, inflamma tion, and antiviral response. It plays a protective role in several forms o f liver damage. In this study, we analyzed NF-kappaB by gel mobility shift assay and immunohistochemistry in liver biopsies from HCV-infected patients , and we have determined the hepatic levels of the components of the NF-kap paB system by semiquantitative polymerase chain reaction (PCR). We found th at NF-kappaB was activated in the liver of patients with chronic hepatitis C. Neither NF-kappaB activity nor the RNA levels of NF-kappaB subunits show ed correlation with liver inflammatory activity, viral load, or HCV genotyp e. By contrast, hepatic mRNA values of RelA, the main element of active NF- kappaB, correlated inversely with apoptosis (r = -.68; P < .05) and with th e rate of fibrosis progression (r = -.51; P < .04). In intermediate/rapid f ibrosers, RelA mRNA levels were significantly decreased as compared with sl ow fibrosers (P < .003) and with normal livers (P < .03). In conclusion, we found that NF-kappaB is activated in chronic HCV-infected livers, and that the expression of RelA is inversely correlated with liver cell apoptosis a nd with the rate of fibrosis progression. Our data thus suggest that RelA e xpression may protect against liver fibrosis and hepatocellular damage.