Immunohistochemical detection of HCV in nerves and muscles of patients with HCV associated peripheral neuropathy and myositis

Abstract

Background: Chronic hepatitis C Virus (HCV) infection may be associated with numerous extrahepatic manifestations, such as mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, sicca syndrome. Cryoglobulinaemia (CG) is a condition characterized by the presence of serum proteins that reversibly precipitate in the cold. The objective of the present work was to study the histopathological changes in neuromuscular biopsies in patients with HCV associated peripheral neuropathy, or myopathy; with and without cryoglobulinemia, and to assess the presence of HCV in nerve and muscle tissues of those patients which might clarify some pathogenetic mechanisms for neuropathy, and myopathy associated with HCV.

Methods: The study was conducted on 17 cases of HCV infected patients with peripheral neuropathy and myositis. All patients were subjected to thorough laboratory investigations, neurological examination, electrophysiologic studies including nerve conduction, and needle EMG studies.

Results: Histopathological examination of nerve biopsies showed features of vascultis in 2/10 cases, interstitial inflammatory infiltrates in 5/10. Muscle biopsies showed intense inflammatory reaction, degenerative changes in the muscles of 3/10 cases diagnosed as myositis. Immunohistochemical results, showed in nerve biopsies, 7/10 cases with positive reaction for HCV with nuclear and perinuclear staining.. Two patients showed positive reaction in the epineural, and endoneural blood vessels and a negative reaction in nerve bundles, while in five patients, reaction was only positive in the nerve bundles. In muscle biopsies, 7/10 cases showed positive reaction for HCV in the nuclei of the muscle fibers, including the cases presented with myositis.

Conclusion: The presence of HCV particles in nerve and muscle biopsies of patients with peripheral neuropathy suggests a virus triggered immune mediated mechanism.

Fig (1).. A case of myositis showing degenerated muscle fibers, nuclear changes, interstitial inflammatory infiltrates and fibrosis (H&E stain 40X).

Fig (2).. Liver biopsy from a patient with HCV infection showing positive nuclear reaction in the hepatocytes, portal inflammatory cells (immunostaining by streptavidin biotin method) 20 X.

Fig (3).. A case of PN showing positive immunostaining of HCV in the blood vessels wall and negative reaction in nerve bundles 20 X

Fig (4).. Another case of PN showing positive reaction in smooth muscle cells of tunica media.40X

Fig (5).. Nerve trunk showing strong nuclear immunostaining for HCV. 40X

Fig (6).. Muscle bundles showing diffuse and strong nuclear immunostaining of HCV in skeletal muscle fibers. 20X

Fig (7).. Muscle biopsy in a case of myositis showing focal mild nuclear immunopositivity in muscle fibers 20 X.