Extrahepatic manifestations of Hepatitis C virus infection: the slowly unraveling picture of oral lichen planus.

To the Editor: Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations. Nevertheless, although several epidemiological arguments suggest that HCV could be implicated in their pathogenesis, existing studies have not been able to determine whether, and by which mechanisms, it plays a direct causal role. With regard to oral lichen planus (OLP), many studies performed mainly in Italy, Japan, Spain have described a strong epidemiological association with HCV infection. On the contrary other reports from different geographic areas, as well as some from the same countries, have found no significant correlation between these conditions. Thus, controversies still exist as to whether HCV infection can have a role in OLP pathogenesis. However, new epidemiological data on the real prevalence of HCV infection in Southern Italy are now available [1–4]. In this context, we have compared the epidemiological features of HCV infection in 600 OLP patients (390 women and 210 men; mean age 52.6 years, range 18–83 years) with the prevalence of HCV infection in general population in order to extrapolate new results towards the association with OLP. All cases had characteristic oral lichenoid lesions and underwent oral biopsy that confirmed the diagnosis. No patient, on the basis of histopathological features and clinical data, was suspected of having drugor restoration-related lichenoid reactions. Subject were screened for the presence of anti-HCV by a second generation enzyme-linked immunosorbent assay (ELISA II; Orto Diagnostic and Chiron Corp., Emerville CA, USA) according to manufacturer’s instructions. Anti-HCV immunoreactivity by enzyme immunoassay was confirmed by a supplemental second-generation recombinant immunoblot assay (RIBA 2; Orto Diagnostic and Chiron Corp., Emerville CA, USA). Differences in proportion between OLP patients and the control group were evaluated using the chi-squared test. A P-value of ,0.05 was considered significant. Of the total of 600 OLP patients studied, 169 tested anti-HCV reactive with ELISA II; among these, 165 tested positive with RIBA and four had indeterminate results. Thus, the overall anti-HCV ELISA II-positive RIBAconfirmed prevalence was 27.5% (165 of 600 subjects). Categorizing OLP patients in five age groups, the prevalence was 0.0% (0/3) in subjects younger than 30 years, 4.6% (3/65) in 30–39 years age group, 12.5% (15/120) in 40–49 years age group, 27.5% (55/200) in 50–59 years age group and 43.3% (92/212) in those older than 60 years. With regard to the control group, it is important to notice that, in recent years, the real prevalence of HCV infection in the general population of Southern Italy has been newly assessed by three studies performed in the Calabria, Campania and Apulia regions over more than 3800 subjects on the whole [2–4]. They have evidenced one of the highest overall anti-HCV prevalence rates compared with figures from other countries, reporting that the average prevalence of HCV infection in this area ranges from 12.6 to 26.0% with a clear age-distribution. In fact, the age-specific prevalence of HCV infection in Southern Italy ranges from 0 to 1.3% in subjects younger than 30 years, from 2.3 to 10.9% in 30–39 years age group, from 5.0 to 25.9% in 40–49 years age group, from 18.4 to 34.5% in 50–59 years age group and from 33.1 to 42.1% in those older than 60 years. The average prevalence, according to the same age groups, are 1.30, 8.45, 19.9, 30.2, and 37.7%, respectively. Comparing these data with those underlined in our study over 600 OLP patients, the emerging picture is that of a strong similarity, without statistically significant differences (P 1⁄4 0:05) (Fig. 1). So, to understand whether OLP is really epidemiologically associated with HCV infection, we have to avoid the error of looking at the overall anti-HCV prevalence in the general population, and we need to compare the single age groups and the age-specific prevalence of HCV infection. What emerges from our 600 OLP patients, which is to our knowledge the biggest group of OLP patients in Italy, reflects the age-specific average prevalence of HCV infection in the general population of Southern Italy. These epidemiological findings point out a lack of evidence for an association between OLP and HCV infection in Southern Italy and seem to suggest that the data previously reported in Southern Italy and other HCV hyperendemic regions may be explained by the high prevalence of HCV infection in these areas. As consequence, our findings suggest that the reported epidemiological association between OLP and HCV infection may be merely casual and that OLP may not be categorized among extrahepatic manifestations of HCV infection, as reported in previous non-epidemiological studies. Nevertheless, we have to accept that OLP may have a different clinical behavior in patients with HCV infection and/or in those treated with interferon for hepatitis C, as we and other authors have described [5], hypothesizing a role of HCV and/or the interferon therapy in the modulation of the Journal of Hepatology 37 (2002) 412–416