Peripheral neurotoxicity of pegylated interferon alpha: A prospective study in patients with HCV
FrancoGemignani, Department of Neurology, University of Parma, Department of Neurology, University of Parma, 43100 Parma, Italyfranco.gemignani@unipr.it
Adriana Marbini
Submitted December 04, 2006
We read with interest the article by Briani et al which showed that
pegylated interferon alpha (PEG-IFNa) therapy was not associated with the
occurrence or worsening of peripheral neuropathy or antibodies to
peripheral nerve antigens in patients with hepatitis C virus (HCV). [1] This is important to dissipate major concerns about treating with PEG-IFNa
patients with peripheral neuropathy.
In this regard, the recent guidelines
of the Italian Association of the Study of Liver (AISF) Commission on
Extrahepatic Manifestations of HCV infection state that "IFN should be
carefully administered to patients with severe sensorimotor neuropathy." [2] This is probably an overstatement considering that there is a
rationale to treat with IFN such patients, as this therapy may eradicate
HCV and cryoglobulinemia that are implicated in the pathogenesis of
peripheral neuropathy, with benefit to the neuropathy itself. [3]
Overall, these data favor a less cautious approach to IFN treatment of
patients with neuropathy and HCV infection. However, some aspects remain
to be explored as to neuropathy during IFN treatment, a likely
idiosyncratic event demonstrated by occasional, but well documented,
reports. [1] It is noteworthy that most reported
HCV patients with IFN-induced or worsened neuropathy had cryoglobulinemia.
In our series of patients with cryoglobulinemic neuropathy [4], a possible
IFN-induced or worsened neuropathy was seen in 3 of 16 treated cases
(unpublished data).
Thus the focus should be shifted on the possible risk during IFN
treatment for patients with HCV-related cryoglobulinemia to develop
neuropathy and for patients with cryoglobulinemic neuropathy to worsen.
The study of Briani et al [1] is not informative on this aspect, as
they included only six patients with cryoglobulinemia (three with
neuropathy) in the treated group.
The conclusive step should be to investigate the occurrence or worsening
of neuropathy during IFN treatment restricted to patients with
cryoglobulinemia and the role of possible risk factors such as
parameters of disease activity including cryocrit, complement levels, and rheumatoid
factor.
References
1. Briani C, Chemello L, Zara G, et al. Peripheral neurotoxicity of
pegylated interferon alpha. A prospective study in patients with HCV.
Neurology 2006;67:781-785.
2. Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB, for the Italian
Association of the Study of Liver (AISF) Commission on Extrahepatic
Manifestations of HCV infection. Extrahepatic manifestations of Hepatitis
C Virus infection: A general overview and guidelines for a clinical
approach. Dig Liver Dis 2006 (e-pub ahead of print)
doi:10.1016/j.dld.2006.06.008
3. Khella SI, Frost S, Hermann GA, et al. Hepatitis C infection,
cryoglobulinemia, and vasculitic neuropathy. Treatment with interferon
alfa: case report and literature review. Neurology 1995;95:407-411.
4. Gemignani F, Brindani F, Alfieri S, et al. Clinical spectrum of
cryoglobulinaemic neuropathy. J Neurol Neurosurg Psychiatry 2005;76:1410-
1414.
Disclosure: The authors report no conflicts of interest.
We read with interest the article by Briani et al which showed that pegylated interferon alpha (PEG-IFNa) therapy was not associated with the occurrence or worsening of peripheral neuropathy or antibodies to peripheral nerve antigens in patients with hepatitis C virus (HCV). [1] This is important to dissipate major concerns about treating with PEG-IFNa patients with peripheral neuropathy.
In this regard, the recent guidelines of the Italian Association of the Study of Liver (AISF) Commission on Extrahepatic Manifestations of HCV infection state that "IFN should be carefully administered to patients with severe sensorimotor neuropathy." [2] This is probably an overstatement considering that there is a rationale to treat with IFN such patients, as this therapy may eradicate HCV and cryoglobulinemia that are implicated in the pathogenesis of peripheral neuropathy, with benefit to the neuropathy itself. [3]
Overall, these data favor a less cautious approach to IFN treatment of patients with neuropathy and HCV infection. However, some aspects remain to be explored as to neuropathy during IFN treatment, a likely idiosyncratic event demonstrated by occasional, but well documented, reports. [1] It is noteworthy that most reported HCV patients with IFN-induced or worsened neuropathy had cryoglobulinemia.
In our series of patients with cryoglobulinemic neuropathy [4], a possible IFN-induced or worsened neuropathy was seen in 3 of 16 treated cases (unpublished data). Thus the focus should be shifted on the possible risk during IFN treatment for patients with HCV-related cryoglobulinemia to develop neuropathy and for patients with cryoglobulinemic neuropathy to worsen. The study of Briani et al [1] is not informative on this aspect, as they included only six patients with cryoglobulinemia (three with neuropathy) in the treated group. The conclusive step should be to investigate the occurrence or worsening of neuropathy during IFN treatment restricted to patients with cryoglobulinemia and the role of possible risk factors such as parameters of disease activity including cryocrit, complement levels, and rheumatoid factor.
References
1. Briani C, Chemello L, Zara G, et al. Peripheral neurotoxicity of pegylated interferon alpha. A prospective study in patients with HCV. Neurology 2006;67:781-785.
2. Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB, for the Italian Association of the Study of Liver (AISF) Commission on Extrahepatic Manifestations of HCV infection. Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach. Dig Liver Dis 2006 (e-pub ahead of print) doi:10.1016/j.dld.2006.06.008
3. Khella SI, Frost S, Hermann GA, et al. Hepatitis C infection, cryoglobulinemia, and vasculitic neuropathy. Treatment with interferon alfa: case report and literature review. Neurology 1995;95:407-411.
4. Gemignani F, Brindani F, Alfieri S, et al. Clinical spectrum of cryoglobulinaemic neuropathy. J Neurol Neurosurg Psychiatry 2005;76:1410- 1414.
Disclosure: The authors report no conflicts of interest.