Molecular evidence that the hepatitis C virus replicates in the oral mucosa

BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have extrahepatic manifestations, which significantly contribute to HCV-related morbidity, but whose pathogenesis is largely unknown. Our aim was to evaluate the HCV replication in oral mucosa of chronic hepatitis C patients. METHODS: We collected oral mucosa specimens from 17 anti-HCV-positive and four anti-HCV-negative patients. Fifteen had oral lichen (12 anti-HCV-positive). Total mucosa RNA was extracted and analyzed for presence and titer of genomic and negative-strand HCV RNA. Findings were compared with clinical and pathological features. RESULTS: Genomic and negative-strand HCV RNA were detected, respectively, in 12 of 17 (70.6%) and four of 17 (23.5%) specimens from the chronic hepatitis C patients. No negative-strand HCV RNA was detected in five anti-HCV-positive patients without lichen (including three with normal mucosa). Presence and titer of the negative-strand HCV RNA were independent of HCV genotype, serum viral load, and histological diagnosis of liver lesions. The phylogenetic analysis of the envelope 2 region cloned from a normal mucosa and the corresponding serum further suggested that only lichen tissues appear to harbor replicating HCV. CONCLUSIONS: HCV may occasionally replicate in oral lichen tissue, possibly contributing to the pathogenesis of mucosa damage.