The prevalence of anti-hepatitis C virus (HCV) antibody in patients with alcoholic liver disease (ALD) may be much higher than that of the general population. Recent evidence suggests that this is largely due to a increase in the prevalence of HCV infection in this population rather than false positive assay results. Furthermore, HCV infection in alcoholics may be associated with histopathologically advanced liver disease, suggesting a role for HCV in the development or progression of liver disease in a subset alcoholics. The relationship of antibody response to active HCV replication in patients with ALD is poorly characterized; however, in patients with alcoholic liver disease, there may be a significant number of chronically infected individuals who fail to produce detectable anti-HCV antibody. It is not yet known what role ALD-induced immune suppression plays in the suppression of anti-HCV antibody response. We propose to use a PCR assay, an anti-HCV EIA, and a recombinant immunoblot assay (RIBA) anti-HCV confirmatory test to study the prevalence of HCV infection and the antibody response to it in patients with ALD. We propose to study the role of risk factors in the development with ALD. We further propose to investigate the effects of alcoholic liver disease-induced immune suppression on HCV infection: by measuring the proportion of subjects with concomitant ALD and HCV infection who fail to produce measurable anti-HCV antibody, by measuring the HCV viral titer in subjects with and without measurable antibody response to the HCV virus, and by measuring the in vitro B-cell response to pokeweed mitogen and the in vivo primary and secondary responses to hepatitis B surface antigen in the same subject groups. Results from these studies will allow us to better understand potentiating factors in the development of ALD and will help clarify the role of alcoholic liver disease-induced immune suppression in modulating the antibody response to HCV infection.
| Snell, L D; Tabakoff, B; Hoffman, P L (1994) Involvement of protein kinase C in ethanol-induced inhibition of NMDA receptor function in cerebellar granule cells. Alcohol Clin Exp Res 18:81-5 |
