Association between B and/or C chronic viral hepatitis and oral lichen planus

MICÓ-LLORENS JM , DELGADO-MOLINA E, BALIELLA-COMELLAS C, BERINI- AYTÉS L, GAY-ESCODA C. ASSOCIATION BETWEEN B AND/OR C CHRONIC VIRAL HEPATITIS AND ORAL LICHEN PLANUS. MED ORAL 2004;9:183-90.

SUMMARY

Introduction: The chronic liver disease is a pathology produced, mainly, by the alcohol chronic abuse and by the hepatitis B and/or C virus infection. In the last years, it has been widely discussed the possible association between chronic liver disease and oral lichen planus. Recently, it has been suggested that the association between oral lichen planus and liver disease has a viral origin.
Material and method: The objective of this transversal matched study is to know if there is a relationship between B and/or C viral chronic hepatitis and oral lichen planus. Two groups of 100 patients were selected: a case group with patients infected with hepatitis B and/or C virus, and a control group without liver disease matched in age and gender. Oral cavity was explored to detect lichen planus in both groups, but we registered other mucosal alterations.
Results: We did not found any patient of the case group with oral lichen planus, but four patients with this disease in the control group.
Conclusions: In our study we did not found any association between the infection with the hepatitis B and/or C virus and oral lichen planus.

Key words: Oral lichen planus, hepatitis B, hepatitis C.

INTRODUCTION

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease of unknown etiology and frequent oral manifestations (1,2). The prevalence of oral lichen planus (OLP) is unclear, since in many cases the condition is not associated to clinical manifestations of any kind (3). In effect, approximatel y 82% of patients are asymptomatic or refer only nonspecific discomfort such as roughness, tension or a dry sensation of the oral mucosa. As a result, the lesions tend to go unnoticed by the patient, the diagnosis being made during a routine visit to the dentist. On the other hand, 18% of affected individuals experience pain - particularly in the presence of extensive, atrophic-erosive and severe lesions (4).

Some studies (3,5-7) have reported a prevalence of OLP in the range of 0.1-3.8% among the general population. The clinical and histopathological features of OLP are characteristic. At present, the lesions are classified as reticular or atrophic-erosive (4). The most common histological findings are the presence of a subepithelial band infiltrate of T lymphocytes and macrophages, with hydropic degeneration of the basal layer (8). The evolution of OLP is generally benign, though occasional cases of malignant degeneration of the atrophic-erosive lesions have been described (9,10). For this reason follow-up with periodic clinical controls is essential in these patients.

A fundamental consideration in the management of OLP is the elimination of potential sources of trauma in proximity to the lesions, such as malpositioned or fractured teeth, or teeth with cutting edges or cuspids, and poorly fitting dentures. It is also important to eliminate tobacco smoking and alcohol consumption, with an optimization of patient oral hygiene (11). Reticular OLP that causes no symptoms should be subjected to periodic controls, with no need for treatment. However, all symptomatic and atrophic-erosive lesions require treatment (12). Regarding medical management of the disease, a great variety of drugs have been used - the most effective options being corticoids, retinoids and topical immune suppressors. Such medication should be administered via the systemic route when topical application fails to yield the desired results (8).

OLP has been associated with certain systemic disorders such as lupus erythematosus, scleroderma, ulcerative colitis, myasthenia gravis, Sjögren's syndrome, pemphigus vulgaris and pemphigoid (13-15). In 1978, Rebora et al. (16) published a case of erosive OLP associated with liver cirrhosis. Since then, many authors (17-35) have debated the relation between OLP and chronic liver disease - though the pathogenesis of LP remains unclear. In recent years an association has been observed between OLP and hepatitis C viral (HCV) infection - particularly in southern Europe and Japan - though no coherent explanation for this relation has been forthcoming to date (36-38). The present study explores the prevalence of OLP in a group of patients with B and/or C hepatitis infection compared with a group of controls without liver pathology. 

MATERIAL AND METHODS

The present study was carried out in the Service of Digestive Diseases of Príncipes de España Hospital (Bellvitge, Barcelona, Spain) between January-October 2000. The case group consisted of 100 patients with hepatitis B and/or C infection, while the control group consisted of 100 individuals without liver disease who were seen in the dental clinic of their primary care center. The controls were matched by age and sex with the cases. Both oral exploration and data compilation of the subjects participating in the study were carried out by a single explorer.

A study protocol was developed comprising demographic data (full name, date of birth, age and sex), the clinical history number, the medical history and the course of the disease - with special attention to the type of virus causing hepatitis in the patients. Liver disease was in turn classified into three groups, according to the case history or latest biopsy findings: chronic hepatitis, cirrhosis and hepatocarcinoma. Liver transplants were also documented.

On the other hand, the laboratory parameters recorded comprised aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (gGT), alkaline phosphatase (AP), albumin, bilirubin, platelets, erythrocytes, leukocytes, hemoglo-bin, hematocrit and the International Normalized Ratio (INR) of prothrombin time, obtained from a recent blood test. The study protocol also recorded the current medication used by each patient, defining polymedication in those cases where the patient was receiving three or more drugs, and non-polymedica-tion when fewer than three drugs were prescribed.

The prognosis of chronic liver disease is difficult to assess, due to the multiple different causes of the disease. The prognostic classification most widely used and applicable to patients with cirrhosis is the Child and Campbell classification, posteriorly modified by Pugh (39) (Table 1). This classification assesses clinical and laboratory aspects based on 5 parameters. On summing the points or score corresponding to each, the least seriously ill patient would present a score of 5, while the most seriously ill patient would show a score of 15. The patients are in turn classified as belonging to category A, B and C according to the score obtained (5-6, 7-9 and 10-15 points, respectively). In this way, the prognosis of patients presenting cirrhosis or cirrhosis with hepatocarcinoma corresponds to 5, 2 and 1 year for groups A, B and C, respectively.

Table 1. Prognostic assessment of liver cirrhosis Child-Pugh classification (39).
Tabla 1. Valoración pronóstica de la cirrosis hepática: clasificación de Child-Pugh (39).

 

Finally, the oral cavity was explored to clinically diagnose possible LP lesions, which were divided into reticular or atrophic-erosive.

In the control group, the study protocol comprised the same demographic data, the medical history, and current medication. The oral mucosa was likewise examined to detect possible OLP lesions, among other alterations.

Statistical analysis

The Pearson chi-square test was used for the comparison of qualitative variables, with the Student t-test for the comparison of the means of quantitative parameters. The SPSS version 9.0 statistical package (license no. 7116391) was used throughout.

RESULTS

The most relevant findings regarding the descriptive analysis and clinical characteristics of the patients belonging to the case group are shown in Table 2. 

Table 2. Sample description and general results recorded in the group of cases.
Tabla 2. Descripción de la muestra y resultados generales en el grupo de casos.

 

No cases of oral lichen planus were identified in this group. The Child-Pugh classification scores for the cases are shown in Table 3. 

Table 3. Distribution and scores of patients with cirrhosis or hepatocarcinoma in the group of cases, according to the Child-Pugh classification (39).
Tabla 3. Puntuación y distribución de los pacientes con cirrosis o hepatocarcinoma en el grupo de casos, según la clasificación de Child-Pugh (39).

 

The mean, standard deviation and maximum and minimum values in relation to the blood test parameters of each patient are given in Table 4.

 

Table 4. Blood test parameters in the group of cases.
(AST = aspartate transaminase, ALT = alanine transaminase, gGT = gamma-glutamyl transferase, 
AP = alkaline phosphatase, mkat/l = microkatals per liter, Eryth. = erythrocyte count, Hb = hemoglobin concentration).
Tabla 4. Valores de la analítica sanguínea en el grupo de casos.
(AST=aspartato transaminasa, ALT=alanina transaminasa, gGT=gamma-glutil transferasa, 
FA=fosfatasas alcalinas, mkat/l=microkatales por litro).

 

The characteristics of the controls are shown in Table 5. The distribution of these patients was matched for age and sex with the cases. The control group registered four cases of OLP - all of the reticular type and corresponding to women aged 35, 60, 65 and 75 years. None of these women had diabetes mellitus, and only one was polymedicated.

Table 5. Sample description and general results recorded in the control group.
Tabla 5. Descripción de la muestra y resultados generales en el grupo control.

 

The statistical analysis revealed no significant relation between the presence of OLP and hepatitis B and/or C viral infection. Likewise, no statistically significant association was recorded with respect to any other study variable.

DISCUSSION

Since Rebora et al. (16) first published a case of lichen planus in a patient with liver cirrhosis in 1978, considerable debate has centered on the relation between chronic liver disease and OLP. While some authors (17-23,40-43) support the existence of such an association, others do not (24,44-46). Bagán et al. (4) studied 205 patients with OLP, of whom 22% presented chronic liver disease diagnosed on the basis of transaminase elevation. The cause of chronic liver disease was not specified. In our study, the group of cases showed liver enzyme alterations (AST, ALT, gGT and PA), though no association of any kind was noted between chronic liver disease and the presence of OLP.

As regards the type and aggressivity of OLP in patients with chronic liver pathology, Bagán et al. (47) in another study involving 187 patients showed that the greater the degree of liver impairment according to blood transaminase elevation (AST and ALT), the greater the aggressivity of the OLP lesions. In this context, 62.5% of the individuals with transaminase elevations presented lesions with erosive zones, versus only 37.4% of the patients with OLP but no transaminase elevation (control group). On the other hand, Cottoni et al. (48) suggested that erosive lesions may be due to increased aggressivity of the associated lymphocytic infiltrate. In our study we were unable to corroborate this point, since we recorded no patients with OLP lesions.

In a later study, Bagán et al. (49) found 23% of patients to binfected with the hepatitis C virus in a series of 100 individuals with OLP. The OLP lesions were distributed as follows: cheek mucosa (91.3%), gums (56.5%), tongue (26.7%), lips (8.7%), floor of the mouth (4.3%) and palate (4.3%). In this same study, only 3.4% of 505 patients with hepatitis C infection presented OLP. However, in the group control of 100 patients there was a single case of OLP and 5 cases of hepatitis C. In our study we found no relation between OLP and hepatitis B and/or C infection. This observation is in contradiction to both the above mentioned study published by Bagán et al. (49), and the work of Pawlotsky et al. (50), in which 5% of 61 patients infected with the hepatitis C virus presented OLP. Nevertheless, our control series contained four patients with OLP, in coincidence with the observations of other authors (49) - though in this latter cases the reported percentage was somewhat lower (1%).

Some studies (36-38) have related OLP to hepatitis C, particularly in southern Europe and Japan. However, el Kabir et al. (44), in a study conducted in the United Kingdom, found no relation between chronic liver disease and OLP - this observation suggesting the possible existence of a geographical factor in the association between these two disorders. No logical explanation for this factor has been proposed, though attempts have been made to relate a specific hepatitis C viral genotype to OLP to account for this geographical distribution - with little success to date.

As regards the relation between hepatitis B viral infection and OLP, the study of the Italian Group of Epidemiological Studies in Dermatology (53) explored 577 patients diagnosed with lichen planus and 1008 controls. Patients of any age and sex presenting the hepatitis B surface antigen (HBsAg) were seen to be twice as likely to develop lichen planus than patients who tested negative for this antigen. Rebora et al. (32), in a series of 87 patients with lichen planus, found 27 of them (31%) to be infected with the hepatitis B virus. However, Carrozo et al. (42) recorded no differences in relation to hepatitis B markers in their group of 70 patients with OLP versus a control group of 70 individuals without OLP. In our study no association has been observed between hepatitis B infection and OLP.

The conventional liver function tests provide data regarding hepatocyte integrity (ALT, AST, etc.) and bile formation (AP, GT, etc.). However, with the exception of serum albumin levels and prothrombin time, these tests do not contribute data on liver function. We found no relation between platelet, leukocyte and erythrocyte counts, hemoglobin or INR and OLP. Moreover, it is not possible to contrast these data with those published by other authors, since these parameters have not been addressed to date. Similar considerations apply to the Child-Pugh classification. Regarding polymedication, we have seen that patients with liver disease receive more medication than those who do not have liver pathology - as would be expected. This fact could suggest a greater incidence of lichenoid reactions to drugs in the group of cases, though we recorded no such lesions in our study.

It has been suggested that patients with OLP have a greater incidence of diabetes than the general population (54). The relation between OLP diabetes is controversial, however, since a number of investigators (54,55) indicate that patients with lichen planus exhibit an altered response to oral glucose loading, with glycemia and insulin response curves comparable to those recorded in patients with type II diabetes. Lundström (56) found 28% of his patients with OLP to be diabetic, while only 3% of the subjects without OLP suffered diabetes. However, other authors such as Silverman et al. (3) question this association. None of our four controls with OLP were diabetic.

As regards the prevalence of OLP, some studies (3,5-7) consider the disorder to affected between 0.1-3.8% of the general population. This result is similar to that obtained in our control group, in which 4% of the subjects had OLP.

In this study no association of any kind was noted between OLP and chronic B and/or C viral hepatitis. However, it seems reasonable that a larger sample of patients could possibly reveal an association between the two disorders, as has been described in other studies conducted in our same geographical setting (48).

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