212 volume 1 • issue 2 April / June 2011 •

AbstractAfter the identification of the hepatitis C virus ge-

nome in 1989 and after the first medical publication onthe association between hepatitis C virus and lichen pla-nus (in 1991), medical literature has become controversialon this subject. The present material reviews the litera-ture and the major world point of views reported in thelast 20 years. Recent epidemiological studies indicate thathepatitis C virus is more prevalent in patients with lichenplanus than in control populations. Screening for anti-hepatitis C virus antibodies is a currently recommendedapproach in patients with lichen planus.

Keywords: lichen planus, hepatitis C virus

Lichen planus is a chronic mucocutaneousinflammatory disease, with unknown etiology.It was first described clinically by Wilson in 1869and histologically by Dubreuilh in 1906. So far,numerous theories concerning its etiology havebeen postulated, with the majority of evidencefavoring an immunologic origin. Lichen planuscan involve: oral mucosa, skin, genital organs,hair follicles, nails, oesophagus, urinary tract,nasal mucosa, larynx and eyes (1). The oral mu-cosa in oral lichen planus is highly accesible foran accurate examination. Therefore, oral lichenplanus is ideal for the study of human T-cell-mediated inflammation and autoimmunity.

Oral lichen planus affects women more thanmen and occurs predominantly in adulthood(1,2). Oral lesions can be detected in approxi-mately 50% of patients who initially present skinlesions, however the prevalence of skin lesionsin patients who are primarily seen for oral lichenplanus is lower, ranging from about 10 to 50% inthe reported series. Oral lesions may occur be-fore, at the same time with, or after skin lesions.There are six clinical forms of oral lichen planus:papular (small white papules), reticular (lace-like striae), plaque-like (white plaques resem-

ORAL LICHEN PLANUS AND HEPATITIS C VIRUS: A LITERATUREREVIEW

Daniela Trandafir1, Violeta Trandafir2, D. Gog\lniceanu3

1. Assist. Prof, PhD, Dept. of Oral and Maxillofacial Surgery, Faculty Med. Dent, „Gr. T. Popa” U.M.Ph Iasi2. Assist. Prof, PhD, Dept. of Oral and Maxillofacial Surgery, Faculty Med. Dent, „Gr. T. Popa” U.M.Ph. Iasi3. Prof, PhD, Faculty Medical Dentistry, „Apollonia” University IasiCoresponding author: Daniela Trandafir (e-mail: trandafir.daniela@gmail.com)

bling leukoplakia), atrophic (difusse red lesionsresembling erythroplakia), erosive (extensiveareas of shallow ulceration) and bullous (sub-epithelial bullae) (2). Oral lichen planus is stillconsidered a potentially malignant lesion (3).

A wide range of factors (viruses included)may precipitate the T-cell-mediated inflamma-tory reaction of the stratified squamous epithe-lium, resulting in lichen planus lesions. So far,several correlations between viral infections (in-cluding the Epstein-Barr virus, cytomegalovirus,varicella zoster virus, human herpes virus, hu-man papilloma virus, human immunodeficiencyvirus, hepatitis viruses) and oral lichen planuswere reported. The most frequent correlationseems to be highlighted between hepatitis C vi-rus infection and oral lichen planus (4). If thiswould be a true association, oral lichen planusmay be viewed as a sign of hepatitis C virus in-fection in asymptomatic patients, allowing earlydiagnosis and treatment and possibly their bet-ter prognosis (4-6).

The first description of the association be-tween hepatitis C virus and oral lichen planuswas published in 1991 (7), but several controver-sies still exist on this relationship. Studies re-ported in the last 10 years conclude a statisticallysignificant correlation between the presence oflichen planus and hepatitis C virus infection (8-12). However, there are researchers who estab-lished no correlations between chronic hepatitisC virus and lichen planus (13-17). A recent meta-analysis revealed an important association be-tween hepatitis C virus and lichen planus (18).

Although the liver represents the major site ofviral replication, a broad spectrum of extrahe-patic manifestations is associated with chronichepatitis C virus infection (mixed

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Maxillofacial Surgery

International Journal of Medical Dentistry 213

cryoglobulinemia, membranoproliferativeglomerulonephritis, autoimmune thyroiditis,non-Hodgkin’s lymphoma, neuropathy,lymphoproliferative disorders, porphyriacutanea tarda, lichen planus, sicca syndrome(19,20).

Infection with hepatitis C virus is character-ized by an extremely high propensity of progres-sion to persistent infection, leading to chronicliver diseases, such as liver cirrhosis or hepato-cellular carcinoma. Acute infection is usuallyasymptomatic, with persistent chronic infectiondeveloping in 43-86% of cases. Due to the lack ofsymptoms, the vast majority of chronically-in-fected individuals remain undiagnosed for sev-eral years, until overt complications, secondaryto decompensated liver disease, eventually de-velop. From this point of view, many research-ers believe that evaluating the potential clinicalrole of lichen planus in diagnosing hepatitis Cvirus infection appears as very important. Theskin and oral cavity are easy to observe. Thepresence of cutaneous lichen planus or oral li-chen planus can be potentially used as a markerof hepatitis C virus infection in asymptomaticpatients, leading to a proper diagnosis and earlytreatment and, possibly, to a better prognosis ofchronic hepatitis C (21, 22).

From the meta-analysis data of Shengyuan(18, 23) one can conclude that hepatitis C virusexposure is more prevalent in patients with li-chen planus than in control populations. Thisassociation seems to be present in all regions ofthe world (table I). However, epidemiologicalstudies do not and cannot prove that hepatitis Cvirus and lichen planus are causally-related (23).

If one accepts the conclusion that the preva-lence of hepatitis C virus is higher in patientswith lichen planus than in the normal popula-tion, patients with lichen planus should bescreened for hepatitis C virus. Potential forms ofscreening include taking a history of the risk fac-tors for hepatitis C virus (iv drug use, sex with ivdrug users, history of blood transfusion), deter-mination of serum liver enzymes (alanine-ami-notransferase, aspartate-aminotransferase), sero-logic tests. Lapane (24), cited by Bigby (23),demonstrated that determining a patient’s riskbased on answers to identified risk factors (ivdrug use, sex with iv drug users, history of bloodtransfusion, male sex, age of 30-49 years) andtesting of those with a risk over 7% (based on alogistic regression model) with ELISA tests foranti-hepatitis C virus antibodies is an optimalstrategy.

Early diagnosis and treatment may save livesand may be useful in reducing health care costs.Therefore, patients diagnosed with (oral or cuta-neous) lichen planus should be checked aboutmajor or minor risk factors for hepatitis C virus,after which those with clinically significant riskshould be screened for hepatitis C virus anti-bodies.

References1. Sugerman PB, Savage NW, Walsh LJ, et al. The

pathogenesis of oral lichen planus. Crit Rev OralBiol Med 2002;13(4):350-365.

2. Scully C, Carrozzo M. Oral mucosal disease: Lichenplanus. Br J Oral Maxillofac Surg 2008;46(1):15-21.

3. Gandolfo S, Richiardi L, Carrozzo M, et al. Risk oforal squamous cell carcinoma in 402 patients withoral lichen planus: a follow-up study in an Italianpopulation. Oral Oncol 2004;40(1):77-83.

4. Lodi G, Scully C, Carrozzo M, Griffiths M, SugermanPB, Thongprasom K. Current controversies inoral lichen planus: report of an international con-

TABLE I ESTIMATED PREVALENCE OF HEPATITIS C

VIRUS IN PATIENTS WITH LICHEN PLANUS INDIFFERENT GEOGRAPHICAL REGIONS

Bigby, 2009

REGION

PREVALENCE

OF HEPATITIS C VIRUS IN

POPULATION (%)

RELATIVE RISK OF HEPATITIS C

VIRUS IN PATIENTS WITH LICHEN PLANUS

VERSUS CONTROLS

ESTIMATED PREVALENCE

OF HEPATITIS C VIRUS IN

PATIENTS WITH LICHEN PLANUS

(%) EAST AND

SOUTHEAST ASIA

2.2 4.3 9.5

SOUTH AMERICA

1.7 5.8 9.9

SOUTH ASIA 2.2 3.8 8.4 MIDDLE EAST 4.6 5.1 23.5

EUROPE 1.0 4.2 4.2 AFRICA 5.3 3.2 17.0 NORTH

AMERICA 1.7 3.6 6.1

OVERALL 3.1 4.8 14.9

ORAL LICHEN PLANUS AND HEPATITIS C VIRUS: A LITERATURE REVIEW

214 volume 1 • issue 2 April / June 2011 •

sensus meeting. Part 1. Viral infections andethiopathogenesis. Oral Surg Oral Med Oral PatholOral Radiol Endod 2005;100(1):40-51.

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7. Mokni M, Rybojad M, Puppin D Jr, et al. Lichen pla-nus and hepatitis C virus. J Am Acad Dermatol1991;24(5):792.

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12. Lin LH, Lu SY, Lu SN. Seroprevalence of anti-HCVamong patients with oral lichen planus in South-ern Taiwan. Oral Surg Oral Med Oral Pathol OralRadiol Endod 2010;109(3):408-414.

13. Michele G, Carlo L, Mario MC, Giovanni L, PasqualeM, Alessandra M. Hepatitis C virus chronic in-fection and oral lichen planus: an Italian case-control study. Eur J Gastroenterol Hepatol2007;19(8):647-652.

14. Das A, Das J, Majumdar G, Bhattacharya N, NeogiDK, Saha B. No association between seropositiv-ity for hepatitis C virus and lichen planus: a casecontrol study. Indian J Dermatol Venereol Leprol2006;72(3):198-200.

15. Cunha KS, Manso AC, Cardoso AS, Paixao JB,Coelho HS, Torres SR. Prevalence of oral lichenplanus in Brazilian patients with HCV infection.Oral Surg Oral Med Oral Pathol Oral Radiol Endod2005;100(3):330-333.

16. Bokor-Bratic M. Lack of evidence of hepatic diseasein patients with oral lichen planus in Serbia. OralDis 2004;10(5):283-286.

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23. Bigby M. The relationship between lichen planusand hepatitis C clarified. Arch Dermatol2009;145(9):1048-1050.

24. Lapane KL, Jakiche AF, Sugano D, Weng CSW,Carey WD. Hepatitis C infection risk analysis:who should be screened? Comparison of multi-ple screening strategies based on the NationalHepatitis Surveillance Program. Am JGastroenterol 1998;93(4):591-596.

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Daniela Trandafir, Violeta Trandafir, D. Gog\lniceanu