ChiaraBriani, Dept. of Neurosciences, University of Padova, Via Giustiniani, 5 - 35128 Padova, Italychiara.briani@unipd.it
Submitted December 04, 2006
We thank Drs. Gemignani and Marbini for their interest in our article
on pegylated interferon alpha (PEG-IFNa) in HCV patients. [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 HCV
patients.
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 HCV patients 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 2 of 3 patients with neuropathy and did not observe occurrence of
neuropathy in any other subject. In another study on 9 patients with HCV-
cryoglobulinemia on a higher IFN-alpha dosage, Cacoub et al [6] reported a
dramatic improvement in 3 of the 7 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 virological response was
associated with a complete clinical response, whereas renal involvement, a
glomerular filtration rate ¡Ü 70 mL/min, proteinuria, and corticosteroid
use were negatively associated with response to IFN-alpha.
In a
multivariate analysis, an early virological 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, since neurological
manifestations did not develop or worsen in any patients. Until possible
predictors of the neurological response to IFN-alpha therapy are
identified, a close electrophysiological follow-up is recommended.
References
5.Mazzaro C, Zorat F, Caizzi M et al. Treatment with peg-interferon
alfa-2b and ribavirin of hepatitis C virus-associated mixed
cryoglobulinemia: a pilot study. J Hepatol. 2005;42:632-638.
6.Cacoub P, Saadoun D, Limal N, Sene D, Lidove O, Piette JC.
PEGylated interferon alfa-2b and ribavirin treatment in patients with
hepatitis C virus-related systemic vasculitis. Arthritis Rheum.
2005;52:911-915.
7.Saadoun D, Resche-Rigon M, Thibault V, Piette JC, Cacoub P.
Antiviral therapy for hepatitis C virus-associated mixed cryoglobulinemia
vasculitis: A long-term followup study. Arthritis Rheum. 2006;5:3696-3706
[Epub ahead of print]
Disclosure: The author reports no conflicts of interest.
We thank Drs. Gemignani and Marbini for their interest in our article on pegylated interferon alpha (PEG-IFNa) in HCV patients. [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 HCV patients.
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 HCV patients 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 2 of 3 patients with neuropathy and did not observe occurrence of neuropathy in any other subject. In another study on 9 patients with HCV- cryoglobulinemia on a higher IFN-alpha dosage, Cacoub et al [6] reported a dramatic improvement in 3 of the 7 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 virological response was associated with a complete clinical response, whereas renal involvement, a glomerular filtration rate ¡Ü 70 mL/min, proteinuria, and corticosteroid use were negatively associated with response to IFN-alpha.
In a multivariate analysis, an early virological 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, since neurological manifestations did not develop or worsen in any patients. Until possible predictors of the neurological response to IFN-alpha therapy are identified, a close electrophysiological follow-up is recommended.
References
5.Mazzaro C, Zorat F, Caizzi M et al. Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study. J Hepatol. 2005;42:632-638.
6.Cacoub P, Saadoun D, Limal N, Sene D, Lidove O, Piette JC. PEGylated interferon alfa-2b and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum. 2005;52:911-915.
7.Saadoun D, Resche-Rigon M, Thibault V, Piette JC, Cacoub P. Antiviral therapy for hepatitis C virus-associated mixed cryoglobulinemia vasculitis: A long-term followup study. Arthritis Rheum. 2006;5:3696-3706 [Epub ahead of print]
Disclosure: The author reports no conflicts of interest.