Interferon  and Ribavirin Combination Therapy in Patients With Chronic Hepatitis C and Mixed Cryoglobulinemia

To the Editor:

Interferon (IFN) monotherapy in chronic hepatitis C is associated with a low rate of sustained biochemical and virological response, which usually ranges between 15% and 25%.1 Recent studies indicate that the combination of IFNα plus ribavirin may increase the success of therapy, particularly in patients who relapse after a first cycle of IFN monotherapy.2 A variable percentage of patients with chronic hepatitis C have circulating cryoglobulins and a minority develop extrahepatic manifestations.3 These patients have been shown to respond poorly to IFN monotherapy, whereas little is known on the effect of IFN-ribavirin combination therapy.

The aim of our study was to assess the effect of IFN-ribavirin combination therapy in patients with hepatitis C and mixed cryoglobulinemia who had failed to respond in a sustained fashion to a previous treatment with IFN alone. We have enrolled 17 patients (13 previous IFN relapsers and 4 previous IFN nonresponders; 12 men and 5 women; mean age, 45.9 ± 13.9 years) with chronic hepatitis (mean HAI score, 6.9 ± 2.1; mean fibrosis score, 1.9 ± 0.9) and mixed cryoglobulinemia (16 with type III and 1 with type II cryoglobulins). As a control group, we studied 19 patients matched by sex and age with chronic hepatitis C (14 previous IFN relapsers and 5 previous IFN nonresponders; mean HAI score, 7.8 ± 3.9; mean fibrosis score, 2.1 ± 0.9) without cryoglobulins in serum.

All patients received as retreatment IFNα-2b (6 MU 3 times per week for 3 months followed by 3 MU 3 times per week for 3 additional months) plus ribavirin (15 mg/kg/d for 6 months).

The results obtained with such retreatment in previous IFN relapsers are shown in Table 1.

Table 1 describes the effect of retreatment with combination therapy on ALT levels, cryoglobulins, and histological parameters. Response rates were very similar in patients with or without cryoglobulins in serum. In patient with cryoglobulins, the biochemical and histological response were associated with a significant reduction in cryocrit values that was transient in relapsers and persistent in sustained responders to the combination therapy. In 5 patients with sustained virological response, cryoglobulins were not detectable in serum at the end of therapy and 12 months later. None of the cases who were previous IFN nonresponders showed end of therapy or sustained response, independently of presence or absence of cryoglobulins in serum.

These results indicate that IFNα plus ribavirin combination therapy is effective in the retreatment of patients with chronic hepatitis C, particularly in previous IFN relapsers, independent of the presence of cryoglobulins in serum. In patients with cryoglobulins, the success of combination therapy was associated with a reduction in cryoglobulins levels and with histological improvement, thus confirming the hypothesis of a direct role of HCV in the pathogenesis of mixed cryoglobulinemia.