The objective of our study was to evaluate the natural history of oral lichen planus (OLP) and other extrahepatic manifestations in the inhabitants of an area in Japan that is hyperendemic for hepatitis C virus (HCV) infection. Over 4 years, 224 adult inhabitants with HCV infection were examined for OLP by a single oral surgeon. All subjects were interviewed regarding the natural history of other extrahepatic manifestations they had developed. The antibodies to HCV (anti-HCV) and serum HCV RNA were determined. Anti-HCV were detected in sera from 224 subjects (100%); HCV RNA in 210 (93.8%). Of the 224, 88 had at least 1 oral examination for OLP during the 4-year period. In 2000, 2001, 2002 and 2003, OLP was observed in 8.5 (5/59), 14.8 (8/54), 20 (11/55) and 21.4% (12/56) of subjects, respectively. OLP prevalence increased as the subjects grew older. The incidence of OLP over the 4 years among all subjects with HCV infection was 17.0% (15/88, 2 men and 13 women). None experienced natural healing or the development of malignant transformations. Between 2000 and 2003, there was an increase in the prevalence of type 2 diabetes mellitus (DM), thyroid dysfunction, skin disease, renal disease and hypertension. Screening for extrahepatic manifestations should be conducted in patients with risk factors for HCV infection.

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