PERIPHERAL NEUROPATHY IN HEPATITIS C VIRUS INFECTED PATIENTS WITH AND WITHOUT MIXED CRYOGLOBULINEMIA

Abstract

Objective: To evaluate immunohistochemical and ultrastructural changes in sural nerve biopsies from patients with peripheral neuropathy and hepatitis C virus (HCV) infection.Methods: Frozen and plastic‐embedded nerve specimens were obtained from 19 HCV‐positive patients with (16) or without (3) mixed cryoglobulinemia (MC). Immunoperoxidase and immunofluorescence studies were performed on cryostat cross‐sections using antibodies recognising cellular subsets and humoral factors involved in the inflammation (CD68, CD11a‐b‐c, CD20, CD3, CD4, CD45, C1q, C3d, TCC, IgG, IgA, IgM). Semi and ultrathin sections were studied by standard protocols.Results: Nerve biopsy showed an axonal degeneration with micro‐ angiopathy (perineurial > endoneurial). IgM and IgG were observed as a thin sub‐perineurial band and in the wall of endo and perineurial vessels in MC patients only. Immunoglobulin deposition colocalised in some nerves with complement factors. Macrophages and T memory/activated lymphocytes were seen perivascularly and in endoneurium while rare B‐cells were detected in perineurium. In the MC‐negative patients, the peripheral neuropathy was characterised by a prominent myelin degeneration. The pattern of distribution of immunoreactivity for humoral and cellular factors was similar but not identical to that of MC patients.Conclusions: Axonal degeneration characterises the HCV‐related MC neuropathy and is likely secondary to ischaemia. The vascular damage is prevailing in perineurium and appears to be mediated by both T‐cells and immune complex. Myelin alterations mainly occur in MC‐negative patients. These last findings suggest a primary pathogenetic role for HCV in the induction of the nerve damage.