nani and Marbini for their interest in our article on pegylated interferon alpha (PEG-IFNa) in patients with HCV. 1 The aim of our study was to evaluate whether PEG-IFN therapy would be associated with worsening or occurrence of neuropathy or autoimmune response to peripheral nerve antigens in patients with chronic hepatitis C. The results did not show any correlation between IFN-alpha therapy and neuropathy in our patients with HCV. We agree with Drs. Gemignani and Marbini that different mechanisms (individual susceptibility, action of the drug, heterogeneity of HCV population, cryoglobulins, vasculitis) may be implicated in IFN-alpha neurotoxicity as we stated in the discussion. Drs. Gemignani and Marbini call our attention to the possible role of cryoglobulinemia as a risk factor for IFN-alpha peripheral neurotoxicity. However, the patient population in our study cannot be used to address this issue. Of the 75 patients with HCV considered, 11 had cryoglobulinemia, only 6 of whom were in the treated group. Recently, however, several studies evaluated IFN-alpha treatment in patients with HCV-related cryoglobulinemia. In a pilot study with PEG-IFN on 18 patients with HCV-associated mixed cryoglobulinemia, Mazzaro et al. 5 reported improvement in two of three patients with neuropathy and did not observe occurrence of neuropathy in any other subject. In another study on nine patients with HCV-cryoglobulinemia on a higher IFN-alpha dosage, Cacoub et al. 6 reported a dramatic improvement in three of the seven patients with polyneuropathy. Finally, the recent long-term study by Saadoun et al. 7 adds further important information. Of 72 patients with HCV-associated cryoglobulinemia treated with IFN-alpha, 44 had neuropathy, 30 (68.2%) of whom showed complete improvement after therapy. None had a worsening of the neuropathy. Moreover, the presence of arthralgia and an early virologic response was associated with a complete clinical response, whereas renal involvement, a glomerular filtration rate 70 mL/min, proteinuria, and corticosteroid use were negatively associated with response to IFN-alpha.

In a multivariate analysis, an early virologic response and the absence of renal insufficiency appeared to be crucial for the clinical response. These data provide clinicians with crucial information that might help select patients with HCV-related cryoglobulinemia that would be likely to respond to IFN-alpha. However, data on the possible factors associated with IFN-alpha neurotoxicity are lacking, as neurologic manifestations did not develop or worsen in any patient. Until possible predictors of the neurologic response to IFN-alpha therapy are identified, a close electrophysiologic follow-up is recommended.