HCV infection and oral lichen planus: a weak association when HCV is endemic G. Campisi, 1 S. Fedele, 2 L. Lo Russo, 2 O. Di Fede, 1 P. Arico `, 3 A. Craxı ` 4 and M. D. Mignogna 1 1 Unit of Oral Medicine, Department of Oral Sciences, University of Palermo, Palermo; 2 Unit of Oral Medicine, Department of Odontostomatological and Maxillo-Facial Sciences, University of Naples ÔFederico IIÕ, Naples; 3 Department of Quantitative Methods for Human Sciences; and 4 GI and Liver Unit, University of Palermo, Palermo, Italy Received October 2003; accepted for publication November 2003 ABSTRACT Oral lichen planus (OLP), an immune-mediated disorder, has been reported as an extra-hepatic manifesta- tion of Hepatitis C virus (HCV) infection, especially in HCV hyperendemic areas such as southern Europe and Japan. The aim of this study was to investigate from an epidemio- logical standpoint whether HCV infection is an important factor affecting the relative risk of OLP in a Mediterranean population or whether this relates to the degree of HCV endemicity. Two cohorts of OLP patients resident in two different regions of southern Italy (Campania and Sicily; n ¼ 859) were evaluated for HCV infection status and cat- egorized into five age classes to respective region-matched controls. No significant difference was found between OLP patients and the general population in this area, when data were corrected by the age-stratified prevalence of HCV. Therefore, the age-specific prevalence of HCV infection in OLP patients shows a close trend of direct association with increasing age, without significant differences with the general population of each geographical area. An aetiologi- cal link between OLP and HCV cannot be inferred solely by epidemiological data. Keywords: hepatitis C virus, epidemiology of HCV infection, oral lichen planus. INTRODUCTION Hepatitis C virus (HCV) infection has been reported in association with many extra-hepatic disorders involving the skin (porphyria cutanea tarda, vitiligo and lichen planus), the eye (Mooren’s ulcer), the kidney (membranous and membranoproliferative glomerulonephritis), the haemopoi- etic system (Hodgkin’s and non-Hodgkin’s lymphoma), the endocrine and exocrine glands (diabetes, thyroiditis, Sjogren-like chronic lymphocytic sialoadenitis), and the immune system (mixed cryoglobulinemias types II and III) [1–9]. Recent evidence from a hospital-based case–control study [10] has seemingly confirmed that at least some of these conditions (namely porphyria cutanea tarda, vitiligo, lichen planus, cryoglobulinemia, non-Hodgkin’s lymphoma and membranoproliferative glomerulonephritis) are epi- demiologically linked to chronic HCV infection, with or without liver disease. However, a clear role for HCV in their pathogenesis has been established only for types II and III cryoglobulinemias, in which binding of the virion to the CD81 transmembrane molecule could act as a B-cell activation signal [11]. Lichen planus is a muco-cutaneous disease whose primary feature is an inflammatory infiltration, mostly made by CD4 cells, localized under the basal epithelial layer. In the oral form of lichen (OLP), HCV replication has been reported in the oral mucosa of anti-HCV/HCV-RNA positive patients. In fact, some studies showed that both the plus and minus strands of viral RNA are detectable in epithelial cells from normal oral mucosa and from the OLP lesions by reverse transcription–polymerase chain reaction [12] or in situ hybridization [13]. As replicative forms of HCV-RNA can be detected within OLP lesions and an immune-mediated damage of basal layer cells is always present in these patients, evidence for a link between the cell-mediated immune response against HCV and the pathogenesis of OLP has been recently reassessed by Pilli et al [14]. They have shown HCV-specific T-cell responses at the site of the OLP lesions, sustained by terminally differentiated effector cells, strongly suggesting their role in the pathogenesis of tissue damage. Although biologically plausible, the link between OLP and HCV remains questionable on clinical grounds. It appears to Abbreviations: EIA, enzyme-linked immunosorbent assay; HCV, Hepatitis C virus; OLP, oral form of lichen; RIBA, recombinant immunoblot assay. Correspondence: Antonio Craxı `, Universita ` di Palermo- Policlinico ÔP. GiacconeÕ, Via del Vespro 129, 90127, Palermo, Italy. E-mail: craxanto@unipa.it Journal of Viral Hepatitis, 2004, 11, 465–470 Ó 2004 Blackwell Publishing Ltd