Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study☆
Introduction
Hepatitis C virus (HCV) determines not only chronic liver disease, but is also implicated in several lymphoproliferative disorders [1], [2], [3], [4], [5], among them the most common is mixed cryoglobulinemia (MC). The treatment of MC includes several drugs like steroids [6], cyclosporins [7], colchicine [8], plasmapheresis [9] and others [10], but given the documented association with HCV virus, the treatment of choice seems to be the antiviral therapy [11], [12], [13], [14], [15]. For chronic hepatitis C, until recently the interferon alfa plus ribavirin was the standard of care [16], but the development of pegylated interferons opened new treatment opportunities [17], even for MC. The aim of this pilot study was to verify safety and efficacy of peg-interferon alfa-2b in combination with ribavirin for initial treatment of HCV-associated MC.
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Patients
Eighteen patients (7 women and 11 men) affected by MC were included in the study. None of the patients had received antiviral therapy in the past (naïve). Diagnosis was based on standard criteria, and showed an active disease, defined as recurrent purpura associated with constant arthralgias and fatigue, despite steroid therapy. In addition to purpura, weakness and arthralgias, eight patients (44%) showed Raynaud's phenomenon, one had ‘sicca syndrome’, three had peripheral sensitive neuropathy
Methods
Values for the liver function tests as well as hematological parameters were determined by usual laboratory methods. Rheumatoid factor (RF), C3 and C4 fractions of complement were measured by rate nephelometry. Cryoglobulin determination was performed according to standard methods as previously reported [19]: the cryoprecipitates, diluted in 0.5 M NaCl, were fractionated by high-resolution gel electrophoresis to type cryoglobulins. Individual monoclonal bands were identified by immunofixation
Biochemical and histological findings
The main clinical, laboratory, and histological findings of patients are captured in Table 1. The age of patients is expressed as years at the start of therapy (mean age 50±11 years). In 3 subjects (17%), no monoclonal component was found; accordingly, in these 3 cases the mixed cryoglobulinemia was defined as type III. A liver biopsy was performed in all patients but one. A chronic liver disease of variable severity was found in all subjects (see Table 1).
Virological findings
HCV-RNA was detected in all subjects
Discussion
This study was performed using a lower peg-interferon alfa-2b dosage in comparison to what was described on HCV updated guidelines [23]. In accordance with our previous experiences, treatment duration was 12 months for all viral genotypes. This therapeutic schedule was adopted in order to enhance drug tolerability and to minimize drop-out rate. Cryoglobulinemic patients are generally older than chronic hepatitis C patients without MC (50±11 years in this series as compared with 42±10 in the
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2017, Clinics in Liver DiseaseCitation Excerpt :Introduced in the early 1980s as a monotherapy, IFN was found to be both poorly tolerated and poorly effective with virologic cure (“sustained virologic response” [SVR]) in fewer than 10%. During the decade 2000 to 2010, pegylated (Peg)-IFN plus ribavirin combination as compared with IFN plus ribavirin showed higher rates of complete clinical and virological responses, regardless of HCV genotype and viral load.37,38 However, the safety profile was not satisfactory and such therapies often led to many severe adverse events, such as severe cytopenia, disabling fatigue, fever, and depression.
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The authors who have taken part in this study declare that they did not receive funding from the manufacturers to carry out their research.