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The aim of this investigation was to determine if an association exists between hepatitis C virus and oral lichen planus.Three groups of subjects were selected: 505 patients with hepatitis C virus infection (group 1), 100 patients with oral lichen planus (group 2), and a randomly selected control group (age- and gender-matched) of 100 healthy subjects (group 3). The prevalence of oral lichen planus was determined in groups 1 and 3, and the prevalence of hepatitis C virus infection was established in groups 2 and 3.The prevalence of oral lichen planus was 3.36% (n = 17) in group 1 and 1% (n = 1) in the control group; the prevalence of hepatitis C virus infection was 23% (n = 23) in group 2, and 5% (n = 5) in the control group. No significant differences were observed in the incidence of oral lichen planus in group 1 between those patients who received interferon and those who did not. The 17 patients in group 1 who manifested oral lichen planus and hepatitis C virus infection simultaneously exhibited a marked tendency to have only reticular lesions (70.6%), with involvement of the buccal mucosa in 88.2% of these patients, the tongue in 29.4%, and the gingiva in 11.8%. Analyzing a randomized subgroup of 143 patients from group 1 (subgroup 1) that was matched by age and gender with groups 2 and 3, we found that the incidence of oral lichen planus in patients with hepatitis C virus infection (subgroup 1) was greater than in the control group (5.59% vs 1%), though this was not statistically significant (χ2 = 0.119; p = 0.06). In contrast, group 2 exhibited a statistically significant higher incidence of hepatitis C virus infection (23%) than the controls (5%; χ2 = 0.259, p = 0.0002).The prevalence of hepatitis C virus infection in patients with oral lichen planus was greater than in the control series. In our opinion this observation warrants the investigation of potential concomitant hepatitis C virus infection in patients with oral lichen planus.