INTERFERON THERAPY IN HCV-POSITIVE MIXED CRYOGLOBULINEMIA - VIRAL ANDHOST FACTORS CONTRIBUTING TO EFFICACY OF THE THERAPY

Background, In a previous paper we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mi xed cryoglobulinaemia. Aims. We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment. Methods, In 27 females an d 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobuli naemia, bone marrow biopsy and phenotyping of marrow cells were perfor med before treatment and at the end of follow-up. A liver biopsy was o btained from patients showing biochemical signs of chronic liver disea se. The presence of hepatitis C virus was assessed by detection of ser um anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The t reatment schedule was 3 million units of recombinant interferon alpha- 2b three times a week for one year. Follow-lip lasted for I year after the end of treatment. The response was classified as follows: 1) Comp lete response: Disappearance of the cryocrit (or re duction of more th an 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but redu ction of cryocrit of less than 50%. 3) Minor response: Reduction of cr yocrit of less than 20% associated with the disappearance of one or mo re (but not all) signs of vasculitis. Results, Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RN A was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indic ating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6% ). After therapy, 13 (31%) patients achieved a complete response, 23 p atients (55%) a partial response, and 6 patients (14%) a minor respons e. Seven of the responders and all patients showing partial or minor r esponses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete I-emission. B one marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found be tween responders and non-responders/relapsers in terms of age, sex, du ration of the disease, severity of symptoms, liver function tests, rhe umatoid factor or complement levels, while the lack of response was as sociated with the presence of genotype 1b, liver cirrhosis, and high c ryoglobulin level. Conclusions, Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an eff ective agent for the treatment of this disease and seems able to deter mine regression of the lymphoproliferative disorder. The hepatitis C v irus genotype and cryoglobulin level are the most important predictive factors of response to therapy.