Exaggerated immune reactions predict the outcome of interferon therapy in patients with chronic hepatitis C.

HCV plays a key role as chronic antigenic driver in inducing a clonal expansion of B-lymphocytes. The hypothesis that previous immunological pattern, when expression of an exaggerated immune reaction, could affect the response to IFN therapy was tested. Using a longitudinal database, the outcomes of 124 HCV-positive patients, genotype 1b only, with circulating HCV RNA, were analyzed by a retrospective cohort design. Immunological disorder-related clinical features and visceral organ involvement were thoroughly investigated in addition to laboratory data focusing on the presence of cryoglobulins, rheumatoid factor, antinuclear antibody, complement, circulating immunocomplexes and mono-oligoclonal gamma-globulin expansion. Eighty-four patients with and forty patients without abnormal immunological status, presenting a low fibrosis score, were identified. The whole naive population was treated by IFN monotherapy at the classical schedule for six or, alternatively, up to twelve months. Of the 124 patients, 28 showed a sustained response while 50 were non-responders and 46 were relapsers. Particularly, among the 84 patients with abnormalities of the immunological status, skin involvement was detected in 71 patients and hypocomplementemia was found in 69 patients, emerging as independent predictors for the lack of response. Conclusively, a peculiar immunological phenotype, ascertained by clinical and/or laboratory findings, is associated to a lack of IFN response and could be considered a further predictive factor.