Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study

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Background/Aims

The aim of this study is to verify the efficacy and safety of peg-interferon alfa-2b in combination with ribavirin for initial treatment of HCV-associated mixed cryoglobulinemia.

Methods

Eighteen patients (7 women and 11 men) affected by mixed cryoglobulinemia were included in the study and treated with peg-interferon alfa-2b 1.0 μg/kg once a week plus ribavirin (1000 mg daily) for 48 weeks, regardless of the HCV genotype.

Results

At the end of the treatment HCV-RNA became undetectable in 15 patients (83%) and most patients improved clinically. One subject suspended treatment at 13th week due to depression. A large fraction of the patients (8 cases: 44%) relapsed both virologically and clinically a few weeks after the end of therapy. At the end of follow-up, only eight patients (44%) obtained a sustained virological response.

Conclusions

Peg-interferon alfa-2b in combination with ribavirin seems safe and useful for patients affected by mixed cryoglobulinemia, but not as effective as in patients with HCV-positive chronic hepatitis without cryoglobulinemia.

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.

Section snippets

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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    The authors who have taken part in this study declare that they did not receive funding from the manufacturers to carry out their research.

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