Hepatitis C virus infection and oral lichen planus: a report from the Netherlands

The reported frequency of anti-hepatitis C virus (HCV) antibodies in groups of cutaneous lichen planus (CLP) and/or oral lichen planus (OLP) patients varies from about 4% to 65%. Most of these studies have been performed in countries with a high overall prevalence of HCV infection in the general population, such as the southern European countries and Japan. Limited data are available from areas with a low prevalence of HCV infection. Therefore, we investigated the prevalence of HCV infection in a series of 55 patients with OLP in the Netherlands, which apparently has a low prevalence of HCV infection. None of the 55 patients revealed serological evidence of antibodies to HCV. The present data suggest that HCV infection in OLP patients in the Netherlands is probably not very common. A larger study group with a sex- and age-matched control group is required to advise against routine serological examination for HCV infection in Dutch OLP patients.     

Hepatitis C virus infection and lichen planus: a short review

OBJECTIVE: To review the current literature regarding the association of lichen planus (LP) and liver disease, with particular attention to the association of the oral variant of the disease with hepatitis C virus (HCV) infection.
MATERIALS AND METHODS: Available literature of the possible association of LP with systemic disorders, in particular chronic hepatic disease, has been reviewed. RESULTS: LP is sometimes associated with infectious or autoimmune disease and/or neoplasia, however an aetio-logical association between LP and these disorders seems unlikely. A more consistent association exists between LP and chronic hepatic disease. The precise cause of this association is not known. However, in the last 6 years a notable association between HCV infection and LP has been observed, particularly in patients in Spain, Italy and Japan. The pathogenesis of this possible HCV-associated LP is not known, but it may involve a cell mediated response to an altered epithelial antigen.
CONCLUSION: There is now evidence to suggest a significant association between HCV infection and LP in some groups of patients.     

Hepatitis C virus infection and lichen planus: a systematic review with meta‐analysis

Oral Diseases (2010) 16 , 601–612 Objective: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra‐hepatic manifestations including mixed cryoglubulinemia, non–Hodgkin lymphoma, diabetes, porphyria cutanea tarda and lichen planus. The aims of this study were to conduct a systematic review and a meta‐analysis on the prevalence of HCV in lichen planus patients and on the prevalence of lichen planus in chronic HCV infection. Materials and Method: Bibliographic searches were conducted in several electronic databases. Pooled data were analysed by calculating odds ratios, using a random effects model. Results and Conclusions: Thirty‐three studies comparing the seroprevalence of HCV in lichen planus patients and six reporting the prevalence of lichen planus in patients with HCV infection were included in the meta‐analysis. The summary estimate showed that LP patients have significantly higher risk (odds ratio 4.85; 95% confidence interval 3.58–6.56) than controls of being HCV seropositive. A similar odds ratio of having lichen planus was found among HCV patients (4.47; 95% confidence interval 1.84–10.86). Sub‐analyses indicated that variability of HCV/lichen planus association seemed only partially depending on geographic effect.     

HCV genotypes in Italian patients with HCV-related oral lichen planus

Hepatitis C virus (HCV) has high genomic variability and since its discovery, six different "types" and an increasing number of "subtypes" have been reported. HCV genotype may influence viral replication, natural history of disease and response to therapy. Recently, an association between lichen planus (LP) and HCV infection has been suggested, as there is an increased frequency of HCV infection among some groups of patients with LP. in particular from Italy and Japan. These results have not been confirmed by other reports from different geographical areas. Since HCV genotypes have a heterogeneous geographical distribution, we have determined by restriction fragment length polymorphism the genotypes of 39 HCV'-seropositive Italian patients with oral LP in order to establish whether the association between LP and HCV infection is influenced by HCV subtype. Of the 33 (84.6%) viraemic patients. 17 (51%) were infected by HCV subtype Ib. 9 (27%) were infected by HCV subtype 2a. 2 by subtype la and 1 by subtype 2b. In four cases the gel patterns were uninterpretable. This distribution of HCV genotypes is similar to that reported in recent studies of Italian HCV-seropositive patients of unknown LP status, It is concluded from this small sample that the association of lichen planus with HCV infection and its differential geographic distribution is unlikely to be due to infection by a particular HCV genotype.     

Oral lichen planus and hepatitis C virus infection

OBJECTIVE: This investigation was conducted to determine the possible association between oral lichen planus (OLP) and hepatitis C virus infection (HCV) in the population of São Paulo (Brazil). MATERIALS AND METHODS: Three groups of patients were studied: group 1 was composed of 68 patients with OLP lesions; group 2 had 126 patients with HCV infection; and the control group consisted of 898 individuals seeking dental treatment at our school, used to determine the prevalence of lichen planus in the general population. The prevalence of HCV in group 1 was determined and compared with that of the population of São Paulo ( 9 ) Brazilian J Infec Dis 2: 269), while the prevalence of OLP in group 2 was determined and compared with that of the control group. RESULTS: The results showed that the frequency of HCV in OLP patients was 8.8%, significantly higher than in the general population of São Paulo, which is 1.4% (P=0.002), and the frequency of OLP in HCV patients (4.7%) was also significantly higher (P=0.0003) than that of the control group (0.6%). CONCLUSION: These data suggest that, at least in São Paulo, there is an association between OLP and HCV infection.     

Oral diseases associated with hepatitis C virus infection. Part 2: lichen planus and other diseases

Some of the most frequent extrahepatic manifestations of hepatitis C virus (HCV) infection involve the oral region predominantly or exclusively. Part 2 of this review discusses the current evidences regarding the association of lichen planus (LP) and other diseases frequently involving the oral cavity with HCV. Epidemiological data suggest that LP may be significantly associated with HCV infections especially in southern Europe and Japan but not in northern Europe. These geographical differences are possibly influenced by immunogenetic factors, the duration of the HCV infection and the design of the published studies. Because of the fact that most of the studies published are retrospective, it is impossible to establish whether the HCV exposure occurred earlier to or after the onset of disease and more prospective studies are clearly warranted. As the virus may replicate in the skin and oral mucosa and HCV-specific T lymphocytes can be found in the oral mucosa of patients with chronic hepatitis C and LP, HCV may be implicated in the pathogenesis of LP. However, little attention has been paid to the variable effect of therapy with interferon-alpha (IFN-α), with or without ribavirin for LP. Conversely, it is unlikely that other oral diseases such as oral carcinoma, pemphigus and Behcet disease are triggered by HCV.     

Oral lichen planus and hepatitis C virus (HCV) infection: is there a relationship? A report of 10 cases

Ten patients are reported suffering from oral lichen planus (OLP) associated with chronic liver diseases linked to HCV. All patients were affected by varieties of erosive oral lichen planus. In six of these 10 patients the diagnosis of HCV was made as a result of the OLP diagnosis and four of them had unknown, but severe, chronic liver disease. These preliminary data support the possible existence of a relationship between oral erosive lichen planus and HCV infection.     

Prevalence of hepatitis C virus in patients with lichen planus of the oral cavity and chronic liver disease

Lichen planus (LP) may represent a mucosal reaction to a variety of factors including hepatitis C virus (HCV) infection. We compared the prevalence of HCV infection in patients with LP of the oral mucosa and chronic liver disease (LP-CLD) with those suffering exclusively from LP or from chronic liver disease (CLD). A total of 267 outpatients participated in a prospective study. There were 41 patients in the LP-CLD group, 128 in the LP group, and 98 in the CLD group. The diagnosis of LP was based on typical macroscopic and histopathologic features and the diagnosis of liver disease on liver histology. Serum samples were screened for anti-HCV antibodies. In 89 patients, serum HCV RNA was also measured. The overall prevalence of anti-HCV antibodies was 29.2% (78/267 patients). Serum HCV RNA levels were positive in 96.2% of anti-HCV-positive patients and in none of anti-HCV-negative subjects. Anti-HCV-positivity was more frequent in the groups of LP-CLD (78%) and CLD (42.8%) than in the LP group (3.1%). It is concluded that HCV infection plays an etiopathogenetic role in CLD associated with oral LP, whereas according to the present findings, the majority of patients suffering exclusively from oral LP are not infected by the HCV.     

Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection,oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus

OBJECTIVES: Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS: Three groups of OLP patients, (I) OLP-HCV patients (n = 17), (2) OLCSR patients (n = 10) and (3) iOLP patients (n = 14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin-biotin-complex technique. RESULTS: The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION: The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups.     

Hepatitis C virus-associated oral lichen planus: no influence from hepatitis G virus co-infection

There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)-related oral lichen planus (OLP), which appears unrelated to either HCV genotype or HCV epidemiology. The present study investigated whether hepatitis G virus (HGV) co-infection may be a feature of patients with HCV-related OLP, which might explain these phenomena. HGV co-infection was detected in 6 of 39 Italian patients with HCV-related OLP, but the presence of HGV did not influence the clinical presentation of OLP. It is concluded that HGV co-infection is unlikely to influence the clinical detection of HCV-related OLP.     

Oral lichen planus in patients infected or noninfected with hepatitis C virus: the role of autoimmunity

Serum proteins, serum immunoglobulins, anti-nuclear antibodies (ANA), antismooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA), anti-liver-kidney antibodies (LKM), anti-parietal-cell gastric antibodies (APCA), anti-epithelial antibodies and concomitant autoimmune disease were studied in 27 OLP-HCV+ve subjects and in a comparable group of 23 who were OLP-HCV-ve. In addition, all the patients with chronic liver disease who were seropositive for ANA, AMA or LKM were scored using the new aggregate scoring system to detect those with the accepted criteria for the diagnosis of autoimmune hepatitis (AIH). Hypergammaglobulinemia was more frequent in OLP-HCV+ve than in OLP-HCV-ve ( P =0.008) subjects. Serum IgG and IgM levels were higher in HCV+ve than in HCV-ve (respectively, P=0.017 and P=0.018) individuals. However, there was no difference in the frequency of any autoantibody between OLP-HCV+ve and OLP-HCV-ve patients. Overall, immunologically-related abnormalities were found in 17(63%) OLP-HCV+ve and 11(48%) OLP-HCV-ve (P=0.43) patients. Three OLP-HCV-ve and no OLP-HCV+ve patients had score criteria of probable AIH. The present and our previous data suggest that OLP patients with HCV infection neither had evidence of autoimmune liver damage nor had abnormal humoral immune-responses, with the exception of higher than control levels of serum immunoglobulins. Cryoglobulins may be responsible.     

黑龙江地区口腔扁平苔藓患者丙型肝炎病毒感染的检测

目的 检测黑龙江地区口腔扁平苔藓(OLP)患者丙型肝炎病毒(HCV)的感染率,并讨论两者之间的关系。方法 采用双抗夹心酶联免疫吸附试验(ELISA)对本地区62例OLP患者和61例非OLP黏膜病患者及22例健康志愿者进行血清丙型肝炎病毒抗体(HCV-Ab)的检测。结果 口腔扁平苔藓组HCV感染率(9.7%)明显高于非OLP黏膜病组(1.6%)和健康组(0%)HCV感染率(P<0.05)。结论 黑龙江地区OLP的发病与HCV感染存在一定的关系。     

Lack of evidence of hepatic disease in patients with oral lichen planus in Serbia

OBJECTIVE: The reported frequency of chronic liver disease, and particularly, Hepatitis C virus (HCV) infection in patients with oral lichen planus (OLP) shows geographical variation. The aim of this study was to determine the prevalence of chronic hepatic disease, Hepatitis B virus and HCV infection in patients with OLP and control subjects resident in Serbia. PATIENTS AND METHODS: In this prospective study 48 patients with OLP (33 women and 15 men, with a mean age of 49.7 years) and 60 control subjects (38 women and 22 men, with a mean age of 46.7 years) were examined for the presence of serological evidence of chronic hepatic disease, Hepatitis B surface antigen (HBsAg) and anti-HCV seropositivity. RESULTS: All patients with OLP had normal liver function. HBsAg was not found in any of the patients with OLP or control group. None of the patients with OLP or control subjects were HCV seropositive. CONCLUSION: Patients with OLP resident in Serbia do not have evidence of chronic liver disease or infection with HBV or HCV. The exact aetiological role between hepatic disease and OLP remains unclear.     

Human papilloma virus in erosive oral lichen planus

Several types of human papilloma viruses (HPV) have been associated with benign and malignant squamous cell tumours of mucosal epithelium. To identify HPV in erosive oral lichen planus (OLPe), considered as a premalignant lesion, tissues from 20 patients were examined by Southern blot hybridization with 32P-labeled HPV DNA probes. Type 11 was found in 6 of the lesions while HPV types 6, 16 and 18 were not detected in any of the tissues examined. Using a type-specific polymerase chain reaction (PCR) assay for HPV-6, 11, 16 and 18, HPV-11 was detected in 8 of the samples (all of those positive by Southern blot), and, in addition, HPV-6 was found in 5 samples and HPV-16 in 3 samples. Overall, by the more sensitive PCR assay, 65% of samples were positive for HPV DNA. The finding of HPV DNA in many of the samples using two different techniques indicates a high prevalence of HPV in the OLPe afflicted oral mucosa. However, the role of HPV in the pathogenesis of OLPe has yet to be determined.     

HLA‐C/KIR genotypes in oral lichen planus patients infected or non‐infected with hepatitis C virus

Oral Diseases (2011) 17 , 309–313 Objectives: Oral Lichen Planus (OLP) is associated with hepatitis C virus (HCV) infection and resembles graft‐versus‐host disease (GVHD) both clinically and histologically. The killer cell immunoglobulin‐like receptor (KIR) genes encode a family of receptors expressed on NK and T cells and are supposed to play a significant role in GVHD and HCV infection. The aim of this study was to analyze the association among OLP, HCV infection and variants in KIR gene expression. Methods: A total of 81 patients with OLP (36 HCV+ve and 45 HCV?ve) and 217 healthy controls (HCV?ve) were typed for the presence of eight KIR genes and of HLA‐Cw* alleles by polymerase chain reaction‐sequence specific primer. Results: There were no significant differences in the frequency of the KIR genes and HLA‐C1/C2 group alleles between cases and controls. We only found a significant difference in the frequency of the gene KIR2DL2 between HCV+ve and HCV?ve OLP patients. Conclusions: The present data suggest that OLP is not associated with particular KIR genes or with HLA‐Cw* alleles in patients without HCV infection. Contrarily, the role of the genes in OLP‐HCV+ve patients remains unclear and might warrant further researches.     

Periodontal status in patients with oral lichen planus: a study of 90 cases

OBJECTIVE: This study was carried out to relate periodontal status to the oral lesions in patients with oral lichen planus (OLP). MATERIALS AND METHODS: Periodontal status was evaluated in 90 patients with OLP and in 52 controls, in terms of the plaque index (PII), simplified calculus index (CIS) and periodontal disease index (PDI). RESULTS: No significant differences were observed between the two groups as regards the different periodontal indices. The plaque and calculus indices were higher in the more extensive forms of OLP (P = 0.02 and P = 0.012, respectively), and in the presence of gingival involvement (P = 0.004 and P = 0.04). A significant association was also observed between the presence of atrophic-erosive lesions and increased periodontal deterioration (P = 0.037). CONCLUSIONS: Increased plaque and calculus deposits are associated to a significantly higher incidence of atrophic-erosive gingival lesions in patients with OLP.