Oral health in patients with hepatitis C virus infection: an underestimated problem?

Abstract

Hepatitis C virus (HCV) is an enveloped, single-stran-ded RNA virus isolated in 1989 from a chimpanzeechronically infected by contamination with a humanfactor VIII concentrate (Choo et al, 1989). HCV ispresently considered as the main etiologic agent of bothblood-borne and sporadic non-A and -B hepatitis, and isone of the major causes of chronic liver diseaseworldwide. Its overall estimated prevalence reaches3%, representing approximately 170 million of HCV-infected persons worldwide. However, there is a greatgeographic variation in the prevalence of HCV infec-tion. On the basis of studies among blood donors, thelowest anti-HCV prevalence rates (0.01–01%) have beenreported from the UK and Scandinavia, followed byslightly higher rates (0.2–0.05%) in Western Europe,North-America, most areas of Central and SouthAmerica, Australia and South Africa (Wasley and Alter,2000). Intermediate rates of anti-HCV prevalence(1–5%) have been reported from Brazil, Eastern Europe,the Mediterranean area, the Middle East, the Indiansubcontinent, and parts of Africa and Asia, and thehighest HCV prevalence rates have been reported fromEgypt (17–26%) (Wasley and Alter, 2000).When second and third generation diagnostic anti-body assays provided adequate sensitivity and speci-ficity to screen low-risk populations, it rapidly becameclear that HCV infection was more than just a liverdisease (Martin, 1993). Several extrahepatic manifesta-tions of HCV (such as cryoglobulinemia-related le-sions, porphyria cutanea tarda (PCT), lichen planus,sialadenitis, thyroid dysfunctions, diabetes mellitus,lymphomas and peripheral neuropathy) mostly immu-nologically mediated, have been brought to light andthe list appears to increase (Pawlotsky et al, 1995;Hadziyannis, 1997). Interestingly, for several of theseputative extrahepatitic manifestations of HCV infec-tion there is a higher prevalence in the Mediterraneanarea and Japan possibly related to immunogeneticfactors. For example, PCT susceptibility is di•erent inBritish and Italian patients being correlated to muta-tion to the human leukocyte antigen (HLA)-linkedhemochromatosis gene C 282Y in the former and tothe gene H63D and HCV in the latter (Elder andWorwood, 1998).Notably, two of the most frequently reported extra-hepatic manifestations of HCV infection, lichen planus(LP) and sialadenitis, involve predominantly or exclu-sively the oral region.The frequent association of LP with chronic liverdisease (CLD) is well known (GISED, 1990) but nohypothetical pathogenic correlation could be found untilsensitive HCV assays were available. Indeed, LP is notsignificantly associated with Wilson’s disease, hemo-chromatosis or a-1-antitrypsin deficiency whereas theassociation of LP with primary biliary cirrhosis is mostlycaused by the administration of penicillamine (Rebora,1992). There are also few reports of mainly skinlichenoid eruptions following administration of di•erentHBV vaccines (Rebora et al, 1999) but the majority ofpatients with both LP and chronic hepatic disease arenot HBV-infected (del Olmo et al, 1989; Carrozzo et al,1996). Moreover, the recently discovered viruses, hepa-titis G virus or TTV, are not associated with LP (Nagaoet al, 1997; Lodi et al, 2000; Rodriguez-Inigo et al,2001).Controlled studies from Italy (Carrozzo et al, 1996;Mignogna et al, 1998), Spain (Sanchez-Perez et al, 1996;Bagan et al, 1998), USA (Bellman et al, 1995; Chuanget al, 1999; Beaird et al, 2001) and Japan (Tanei et al,1995) have confirmed that HCV is the main correlate ofliver disease in patients with LP, especially oral LP(Carrozzo et al, 1996; Sanchez-Perez et al, 1996). Forunknown reasons, the e•ect of interferon alpha (IFN-a)therapy for HCV infection in patients with LP di•ersmarkedly from case to case. IFN-a has been reported tohave no influence (Pawlotsky et al, 1995), to improve(Hildebrand et al, 1995), to trigger or worsen LP lesions,mainly in cases with oral involvement (Protzer et al,1993; Nagao et al, 1996; Dalekos et al, 1998). Theexacerbation of oral lesions could possibly be related tothe induction of antiepithelial antibodies induced byIFN-a therapy (Fleischmann et al, 1996), but there areno data on this topic. The adjuvant use of ribavirin with