A potential marker of increased histological activity in hepatitis C virus infection

Early, vigorous and sustained lymphocyte proliferative responses specific to hepatitis C virus (HCV) have been regarded as pivotal for viral clearance.

On the other hand, antibody responses' contribution is still controversial. Research data have been accumulated regarding the significance of specific antibody classes during chronic infection. Particularly, the relation of IgA and alcohol-induced hepatic damage has been recognized, but its possible implication in HCV chronic infection has not been explored so far.

A research article to be published on November 28, 2008 in the World Journal of Gastroenterology addresses this question. This article investigated the HCV-specific immune responses in chronic treated and untreated patients, in paired samples taken 6 months apart. IgG, IgM and IgA levels, as well as IgG1-4 subclasses and peripheral blood lymphocyte proliferative responses against core, envelope and NS3 antigens were assayed by ELISA and CFSE staining, respectively.

Over 70% of the patients showed specific IgG and IgM against HCV capsid, E1 and NS3, while the hypervariable region-1 of E2 was recognized by half of patients. Anti-capsid IgM and IgG levels increased over time, while IgA levels did not; instead, an increase in IgA positive samples was observed. Particularly, IgA against HCV structural antigens positively correlated with necro-inflammatory activity. IgG subclasses evaluation against capsid and NS3 revealed that more than 80% of the individuals were positive for IgG1. On the contrary, less than 30% of the patients showed a positive proliferative response of CD4+ and CD8+ T cells, the viral capsid being poorly recognized.

Correlation analysis between demographic variables and humoral response revealed that alcohol consumption was negatively correlated with the responses of the main classes IgM, IgA and IgG, as well as IgG4. On the other hand, presence of specific IgG4 positively correlated with the fact of being treated with the standard therapy and the grade of necro-inflammatory activity. Additionally, the necro-inflammatory activity, also correlated with IgA, while fibrosis did not.

These results confirm that while the cellular immune response is weak and narrow, a broad and vigorous humoral response is present in chronic HCV infection. Particularly, the association of specific IgA response to necro-inflammatory activity paves the way to further studies to confirm its usefulness as a non-invasive, easy-to-measure marker of histological activity in chronic HCV infection.