Dental health In liver transplant patients

DÍAZ-ORTIZ ML, MICÓ-LLORENS JM, GARGALLO-ALBIOL J, BALIELLAS-COMELLAS C, BERINI-AYTÉS L, GAY-ESCODA C. DENTAL HEALTH IN LIVER TRANSPLANT PATIENTS. MED ORAL PATOL ORAL CIR BUCAL 2005;10:66-76.

SUMMARY

Since the first liver transplantation in Spain was carried out in 1984, advances in surgical technique and immunosuppressive drugs have facilitated an increase in the number of transplants performed. The present study evaluates buccodental health in liver transplant patients. A cross-sectional descriptive study was made of a sample of patients subjected to liver transplantation in Príncipes de España Hospital (Bellvitge University Health Care Complex, L’Hospitalet de Llobregat, Barcelona - Spain). Information was collected relating to demographic characteristics, general clinical history, buccodental history and intraoral exploratory findings. A total of 53 individuals were evaluated (28 males and 25 females, with a mean age of 57.6 years). The mean time elapsed from transplantation was 3 years and 9 months. The most frequent indication for liver transplantation was liver cirrhosis due to hepatitis C virus (HCV) infection (49.1% of the global series). The most widely used immunosuppressors were cyclosporine and tacrolimus. The CAOD index of the series was 11.2. In relation to periodontal disease, 22% of the dentate patients showed gingival overgrowth, while half of those with teeth had gingival recessions, and 34% presented some type of dental mobility. The examination of the oral mucosa showed fissured tongue to be the most common disorder (39.6%), followed by saburral tongue (28.3%) and xerostomia (18.9%). Buccodental pathology in these patients is related to the use of immunosuppressor medication and other factors such as a lack of preventive measures. The findings of the present study point to the need for preventive treatments in this population group.

Key words: Liver transplantation, immunosuppression, cyclosporine, gingival overgrowth, oral pathology.

 

INTRODUCTION

Spain is the first country in the world in terms of the number of transplants performed per inhabitant 1. Advances in basic and technological knowledge in the mid-twentieth century led to progressive improvement in organ transplantation techniques. Moreover, advances in immunosuppressive therapies have considerably extended patient survival in recent years (1-3). Liver transplantation programs were first introduced in Spain in Príncipes de España Hospital (Bellvitge University Health Care Complex, L’Hospitalet de Llobregat, Barcelona - Spain) in 1984, and since then there has been a gradual increase in the number of operations carried out. According to the Spanish Liver Transplant Registry of the National Transplant Organization (Registro Español de Trasplantes Hepáticos; Organización Nacional de Trasplantes), in the period 1984-2000 a total of 6850 liver transplants have been carried out in this country (4).

Liver transplantation is a treatment option in many different disease conditions, though the most common indications are chronic liver disorders (biliary and non-biliary cirrhosis), hepatocellular carcinoma and severe acute hepatic failure (1). In Spain, the most frequent indication according to the National Transplant Organization is cirrhosis secondary to hepatitis C virus (HCV) infection, followed by alcoholic cirrhosis (5).

Liver transplant patients require periodic clinical follow-up to control the possible complications of immunosuppressive therapy, such as for example arterial hypertension, diabetes or gingival overgrowth. The prevention of infection is one of the factors decisive to transplantation success. In effect, these patients present immune depression, and at any time microorganisms may induce a potentially life-threatening infectious process (5). Such immune suppression is particularly manifest in the oral cavity, which constitutes one of the most common locations of infectious and neoplastic pathology. It is therefore essential to perform regular oral examinations of these patients (6,7). In this sense, it is very important for the dental professional to know the most frequent oral manifestations of transplant patients, in order to ensure correct management, with adequate communication among all the health care professionals that intervene in the care of such patients (5,6,8).

The present study examines the buccodental health and dental treatment needs of patients who have undergone liver transplantation.

MATERIAL AND METHODS

A cross-sectional descriptive study was conducted in 2001, comprising 53 liver transplant patients reporting for periodic follow-up in the Service of Digestive Medicine of Príncipes de España Hospital (Bellvitge University Health Care Complex, L’Hospitalet de Llobregat, Barcelona - Spain). The exclusion criterion was patient refusal to participate in the study. The evaluations were carried out by a single investigator in one of the outpatient offices of the Service of Digestive Medicine.

The patient data were collected based on a protocol designed to the effect, including demographic particularities (sex and age), general clinical history (time elapsed from transplantation, type of underlying liver disease, and current medication), buccodental history and intraoral exploratory findings. An evaluation was made of whether or not the patient had received recommendations relating to buccodental care before and/or after liver transplantation (and from what health care professional). The existence of regular dental controls was also documented, along with the time elapsed from the last dental revision, and the possible dental treatments provided after transplantation. In the event dental care had been provided, the type of treatment was recorded, along with the possible associated complications or problems. In addition, oral hygiene habits were registered, including the frequency of tooth brushing and the use of mouthrinses and dental floss.

All patients were examined in a chair, with the oral cavity illuminated by an exploratory lamp. The instruments used were two dental mirrors and an exploratory probe per patient, with gloves and a face mask. Oral hygiene was evaluated using the simplified Green and Vermilion index (9), with modifications, since only the coronal extension of supragingival tartar was taken into account. The oral mucosa was explored to identify possible lesions and their location. Xerostomia was defined by manifest dryness of the oral mucosa. The dental conditions were assessed based on the CAOD index. To calculate the latter, all root remains and teeth presenting coronal destruction were regarded as caried teeth (the presence or absence of third molars was not assessed). The diagnosis of caries was based on the use of a dental mirror and exploratory probe. The presence of tooth abrasions and dentures (prostheses) was also taken into account. At periodontal level, the possible presence of gingival overgrowth was recorded, along with the existence of gingival recessions and tooth mobility. The latter was evaluated using the two dental mirror shafts: grade I mobility was defined as 0.2-1 mm horizontal mobility; grade II as over 1 mm; and grade III as axial mobility. No periodontal probing was carried out.

The results of the latest laboratory tests were also recorded, including complete blood count, liver function parameters, and coagulation (prothrombin time and activated partial thromboplastin time (aPTT)). An orthopantomographic study was also requested in the case of patients with some type of buccodental pathology identified at exploration (after obtaining consent), with the evaluation of bone disorders in the form of radiotransparencies, opacities and bone loss. Dental pathology was documented, with assessment of possible impacted teeth (including third molars in this case).

The information regarding disease antecedents and current status was supplied by the medical service caring for the patients. Following exploration, and if the patients presented buccodental disease, a report was prepared for submission to the dental care unit of the supervising primary care center or private dental professional, to facilitate required treatment and periodic controls.

A descriptive statistical study was made, with application of the chi-square and Student t-tests for the comparison of qualitative and quantitative variables, respectively. The SPSS version 9.0 statistical package for Microsoft Windows (University of Barcelona license) was used throughout. Statistical significance was accepted for p <0.05

RESULTS

A total of 53 patients were studied (28 males and 25 females, with a mean age of 57.6 years (standard deviation, SD = 9.1); range 38-71 years)(table 1). All patients were subjected to liver transplantation in Príncipes de España Hospital (Bellvitge University Health Care Complex, L’Hospitalet de Llobregat, Barcelona - Spain). The time elapsed from transplantation ranged from two months to 10 years, with an average of 3 years and 9 months (figure 1). Six patients (11.3%) had received a second liver transplant, while four (7.6%) also received a kidney transplant. figure 2 reflects the indications for liver transplantation. The most common indication was liver cirrhosis secondary to hepatitis C virus (HCV) infection. Of note is the fact that 60.4% of the patients had been infected with HCV.

The patients received an average of 3.4 drugs per individual (SD = 1.6). table 2 shows the drugs prescribed. All medicated patients were administered at least one immunosuppressor.

As to the buccodental health recommendations, 52.8% of the patients claimed to have received such instructions before the transplant (89.3% from the hospital where the operation was performed, 3.6% from a private dentist, and 7.1% from both). Following transplantation, 62% received the same type of recommendations (93.9% from the hospital where the operation was performed, 3% from a private dentist, and 3% from both). Only 18.9% of the patients studied underwent periodic controls by a dentist, with a mean frequency of one visit every 12.7 months. On the other hand, 11.3% of the patients reported their last dental visit to have been less than 6 months previously, while in 30.2% of cases the latest visit was between 6 and 12 months previously (table 3). Only 41.5% of the study subjects had received some kind of dental treatment before liver transplantation. Such treatment comprised extractions in 50%, tartar removal in 40.9%, fillings in 36.4%, dentures in 27.3%, and other treatment modalities in 27.3%. None of these patients reported any type of problem or complication as a result of the treatments provided.

Regarding oral hygiene, figure 3 shows the frequency of tooth brushing. Almost half of the patients (47.2%) used mouthrinses, generally on an occasional basis, and particularly in the form of hexetidine (64%). Only one patient claimed to use dental floss.

At intrabuccal exploration, 40% of the patients studied showed regular oral hygiene, while the latter proved deficient in 34% and correct in only 25.5%, according to the simplified index of Green and Vermilion (9). In turn, 5.7% were totally edentulous, 17% had all their teeth, and the majority (77.4%) were partially edentulous. The CAOD index was 11.2 on average, and although the figure was greater in males than in women, no statistically significant differences were observed between sexes (p=0.18). In these patients, missing teeth were more common than caried or filled teeth (table 4). On the other hand, 32% of the dentate patients had cervical abrasions, while 16% presented incisal facet wear, and 10% generalized dental wear. All totally edentulous patients and 54.6% of the partially edentulous subjects used dentures of some kind.

Examination of the oral mucosa showed pathology to affect mainly the tongue – particularly fissured tongue (39.6%) and saburral tongue (28.3%). Table 5 shows the prevalence of oral mucosal disorders. The category “Others” comprises less frequent lesions such as ulcers, angle cheilitis, diapneusia, palatal hyperplasia, angiomas and geographic tongue, among others.

As regards periodontal disease, 11 of the dentate patients (22%) had gingival overgrowth – localized in 54.6% and generalized in 45.5%. In relation to the type of immunosuppressor prescribed, the greatest prevalence of gingival overgrowth corresponded to those subjects administered cyclosporine and tacrolimus – though no statistically significant differences were observed with respect to the type of immunosuppressor involved (p=0.881). In contrast, significant differences were recorded in terms of the degree of oral hygiene (p=0.026). In effect, 63.6% of the patients with gingival overgrowth presented defective oral hygiene, while in 36.4% of cases hygiene was regular. None of the patients presented correct oral hygiene. Moreover, 90.9% of these patients were not subjected to regular dental follow-up. One half of the dentate patients showed gingival recessions, and 34% had some kind of tooth mobility: grade III in 47.1% of cases, grade II in 29.4%, and grade I in 23.5%.

Thirty orthopantomographic studies were requested, of which only 16 were received. Alveolar crest bone loss was observed in 14 patients (horizontal in all cases), with generalized and localized involvement in 71.4% and 28.6%, respectively. Four patients presented periapical radiotransparencies; in addition, 5 impacted teeth in three patients were identified (4 third molars and one canine).

As to the laboratory test findings, 71.7% of the patients showed aspartate aminotransferase transaminase (AST) elevations (>0.05-0.5 µkat/l), 51% had fewer than 150,000 platelets/ml, and 8.3% presented a prothrombin time of over 15 seconds.

DISCUSSION

The need for permanent immunosuppressive therapy exposes liver transplant patients to a high risk of infections – the latter constituting the first cause of morbidity and mortality in such individuals, fundamentally in the first year after transplantation. The most frequent infections are of a bacterial nature, together with cytomegalovirus (CMV) infection and fungal processes (10.11). In the oral cavity infections tend to be recurrent and are associated to poor oral hygiene (12,13). In terms of frequency, special mention is required of mycotic disease caused by Candida albicans, and viral processes due to herpes virus in the form of recurrent herpetic infections (6,13,14). In the present study, and based on the classification of Homstrup and Axell (15), we observed no case of acute or chronic candidiasis, though candidiasis was diagnosed in association to other lesions. There was one case of angle cheilitis and two cases of palatal inflammation caused by dentures. Both of these conditions are usually characterized by the presence of other causes in addition to candidiasis.

The results obtained showed the tongue to be the most frequent location of oral mucosal disease – particularly in the form of fissured tongue. There was also a high prevalence of saburral tongue, depapillated tongue, hairy tongue and geographic tongue. It should be taken into account that while these disorders are generally asymptomatic, they sometimes may also present Candida overinfection (16,17). We performed no complementary studies such as exfoliative cytology or cultures to determine the presence of the microorganism in these lesions.

Different etiological factors have been implicated in these tongue lesions, including drug administration (e.g., corticoids), the use of mouthrinses, poor oral hygiene, smoking and alcohol. Other factors such as oral environmental pH variations, xerostomia, vitamin A and C and/or calcium deficiencies, or some type of anemia have also been implicated (17-19). In the present study, 28.3% of the patients were receiving some vitamin supplements or were undergoing treatment for anemia. In addition, 18.9% presented oral mucosal dryness that could be related to the use of certain drug substances such as antihypertensive agents. Moreover, two of our patients were diagnosed with Sjögren syndrome.

There are also other frequent side effects of the pharmacological treatment prescribed in liver transplant patients, such as for example gingival overgrowth. The latter can be caused by different substances such as cyclosporine and calcium antagonists (20.21). While these drugs are structurally distinct, they share the same mechanism of action involving the inhibition of cellular calcium reuptake – this mechanism being implicated in the pathogenesis of gingival overgrowth (18). In addition to the high plasma concentrations of cyclosporine, other related factors have been described – such as the presence of bacterial plaque, chronic gingival inflammation and oral hygiene (6,18,21-24). The prevalence of gingival overgrowth due to cyclosporine varies from 10-70%, according to the source in the literature 18. In the present study the prevalence was 54.6%.

Immunosuppressive medication has also been associated to an increased risk of malignancy (2,3,11). In Spain, in a study conducted by the Spanish Liver Transplant Group, a 3.8% incidence of malignant tumors was recorded in liver transplant patients. Despite the fact that the risk of oral cancer is increased in these patients, no such increment was noted in our series. This coincides with the observations of Somacarrena et al. (14), who reported no tumor processes. We did record three cases of leukoplakia, however. In these patients it is important to establish an early diagnosis of oral cancer, with the introduction of adequate preventive measures – eliminating risk factors such as smoking and alcohol (25,26). Special attention should also focus on patients subjected to liver transplantation due to alcohol cirrhosis, since smoking is also common in such individuals (27).

Regarding pre-transplantation recommendations, it is important to evaluate the buccodental condition of the patient and detect the presence of disorders requiring treatment before liver transplantation is carried out. The patients are to be instructed on the need to observe adequate oral hygiene, with warning as to the oral risks and problems that may appear after transplantation (3,13,24,28,29). Barbero et al. (7) examined the buccodental health of 80 patients being prepared for liver transplantation. They found 85% of the patients to have deficient oral hygiene, while 45% presented advanced periodontal disease, and 12% had chronic gingivitis. In addition, 67% of the individuals studied suffered caries, and 20% had periapical lesions. On contrasting these results with our own findings, we recorded fewer patients with poor oral hygiene, caries and/or advanced periodontal disease.

Although all liver transplant patients in Príncipes de España Hospital (Bellvitge University Health Care Complex, L’Hospitalet de Llobregat (Barcelona) - Spain) receive recommendations from the medical personnel on oral care before and after transplantation, and even receive a manual and video, not all patients report having received such instructions or materials (30). We consider that instructions on oral hygiene, with recommendations and motivation for buccodental care, should be provided by specialized personnel, and preferably on a periodic basis to ensure adequate follow-up of each case. If such recommendations are provided on a point basis before and/or after transplantation, they may not be sufficient to adequately motivate the patient – thereby contributing to explain the important proportion of subjects who claimed to have received no such instructions.

Since these patients are at an increased risk of developing buccodental lesions because of the immune suppression therapy involved, exploration of the oral cavity should form part of the multidisciplinary follow-up protocol of liver transplant patients (31). King et al. (31), in a study of 159 kidney transplant patients, observed that only 57.9% underwent periodic controls by a dental professional. In our study the prevalence was even lower (only 18.9%) – thus pointing to the need for improvements in this field.

A series of complications may develop after liver transplantation, including diabetes, obesity, arterial hypertension and hyperlipidemia (3,5). These alterations, when chronic, can in turn lead to systemic problems such as cardiovascular disease. Such patients therefore often require dietary and/or pharmacological treatment – the most widely used drugs being antihypertensive agents. This coincides with our own observations, since 37.7% of the patients were receiving this type of medication (2). Special caution is required when administering calcium antagonists (particularly nifedipine), since gingival overgrowth is one of their documented side effects (32). The prevalence of gingival overgrowth in patients receiving nifedipine is estimated to be 15-20% (21,33). In our study 42.9% of the patients administered this type of medication showed gingival overgrowth. In addition, the incidence and severity of gingival overgrowth increases when some calcium antagonist is prescribed in addition to cyclosporine (21,34).

The high total CAOD index recorded in our study is fundamentally attributable to the important number of missing teeth. The O index (obturated/filled teeth) was very low – thus indicating that few teeth received restorative treatment, or that those teeth subjected to restoration were no longer in the mouth. In this sense, consideration is required of the cost of odontologic treatment and the limitations in public health care coverage of such problems.

The management of buccodental disorders in liver transplant patients is fundamentally palliative and local. It is important to combat xerostomia and infections, and to improve dental and denture hygiene. The local application of chlorhexidine and fluor is also advisable, with the elimination of smoking and alcohol abuse, and the introduction of dietary changes (17,20.28). On the other hand, it has been observed that replacing cyclosporine with some other immunosuppressor such as tacrolimus affords a reduction in gingival overgrowth (35). Thorp et al. (35) achieved a mean reduction in gingival hyperplasia index of 24 six months after replacing cyclosporine with tacrolimus in 16 kidney transplant patients. As to those patients who must remain on cyclosporine, treatment should focus on the prevention and elimination of predisposing factors such as the accumulation of bacterial plaque (36). The elimination of supra- and subgingival tartar and plaque, together with strict oral hygiene and the use of chlorhexidine mouthrinses, can reduce the inflammatory component of gingival overgrowth and may prove sufficient to control the more mild or moderate cases (16,18,24).

Based on the results obtained in our series of patients, it may be concluded that a number of aspects need to be addressed. A first consideration is patient and medical personnel instruction on the importance of oral hygiene and buccodental care. Secondly, dental professionals should be instructed on the care of liver transplant patients, while at the same time ensuring good communication among all the professionals who care for these patients. Lastly, attempts should be made to prevent cost considerations from becoming an obstacle for the dental treatment required by patents with economical limitations (31).

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