Periodontitis in patients with cirrhosis: a cross-sectional study

Periodontitis is an inflammatory disease of multifactorial etiology that affects the supporting tissues of the teeth and is characterized by deepening of periodontal pockets, connective tissue attachment loss and alveolar bone loss [1]. Untreated, periodontitis can result in discomfort, impaired mastication, pain, and eventual tooth loss [1, 2].

Oral health is generally poor in patients with cirrhosis and may lead to oral infections [3‐6]. However, the prevalence and risk factors for periodontitis in cirrhosis are sparsely investigated. In addition, it has been reported that alcoholic cirrhosis and the severity of cirrhosis may contribute to a higher risk of periodontitis, but the relationship has not been substantiated and data are conflicting [7‐10].

Malnutrition and infections are common and serious complications to cirrhosis leading to increased morbidity and mortality [11, 12]. Periodontitis itself may have adverse health effects and it has been associated with malnutrition and systemic inflammation activation in patients with cardiovascular disease, chronic kidney disease, and diabetes [13‐15]. It has not yet been investigated whether periodontitis is similarly associated in cirrhosis.

The aim of the present study, therefore, was to examine the prevalence and identify predictors of periodontitis, and to evaluate the association of periodontitis with nutritional and systemic inflammation status in a cohort of patients with cirrhosis.

We screened 262 patients for eligibility, of which 117 were excluded by the exclusion criteria, lack of consent, death before the oral examination, or edentulism. Figure 1 gives the patient flow. A total of 145 patients were included into the study. Their mean age at baseline was 61 years (range 21–87 years), and 65% were men. Their clinical characteristics and demographic characteristics according to periodontitis status are presented in Table 2.

Forty-six percent of the patients had severe periodontitis, 39% had moderate periodontitis, and only 15% had no-or-mild periodontitis.

There were no differences in age, gender, cirrhosis etiology, cirrhosis severity, smoking status, alcohol use, comorbidity, dental visits, number of teeth, nutritional and inflammation status in patients with severe periodontitis as opposed to patients with no- or-mild and moderate periodontitis. However, patients with severe periodontitis brushed teeth less often, had more plaque, increased probing depth, increased clinical attachment level, and more bleeding on probing than patients without severe periodontitis (Table 2).

Smoking was a predictor of severe periodontitis (odds ratio (OR) 2.93, 95% confidence interval (CI): 1.29–6.63). The same was found for oral health markers in the form of brushing teeth twice daily (OR 0.30, 95% CI 0.11–0.79) and visiting the dentist annually (OR 3.51, 95% CI 1.22–10.81) (Table 3). Cirrhosis etiology and cirrhosis severity were not associated with severe periodontitis (Table 3).

Compared to patients with no-or-mild and moderate periodontitis, patients with severe periodontitis had a higher nutritional risk score (3, interquartile range (IQR) 3–5 vs. 3, IQR 2–4) and lower handgrip strength (22 kg, IQR 16–30 kg vs. 25 kg, IQR 18–35 kg), but only the nutritional risk score was significantly different (P = 0.02 and P = 0.1). Likewise, the median CRP concentration was higher in patients with severe periodontitis than in those without (17.1 mg/L, IQR 5.8–36.6 mg/L vs. 12.4 mg/L, IQR 6.7–27.1 mg/L), but there was no statistically significant difference (P = 0.08) (Table 3).

Figure 2 shows a photograph of severe periodontitis.

This study describes a very high, close to universal, prevalence of periodontitis in patients with cirrhosis independent of cirrhosis etiology and severity. Within the patient population smoking and oral care habits were identified as predictors of periodontitis. In addition, it is the first study to suggest a relationship between periodontitis and nutritional status in cirrhosis patients.

Previous authors have recorded periodontal disease in 32–52% of their cirrhosis cohorts [5, 8] but unfortunately, a direct comparison is difficult because periodontitis is defined by different criteria. No definition, measures, or indices have gained universal approval [24]. In this study we used the definition proposed by the CDC/AAP [17]. This definition is becoming more widely used making comparisons between our and future studies possible [25].

In this study, all of the periodontal disease indicators (plaque, BOP, PD, CAL) were involved, indicating full clinical penetrance of periodontitis. Diagnostic uncertainty notwithstanding, the prevalence of periodontitis in this study population was markedly higher than the 10–15% in the adult general population worldwide [26, 27]. Thus, the improvement in the general population’s oral health during the past decade [28] is not followed by a similar improvement in patients with cirrhosis.

Alcoholic cirrhosis was not associated with severe periodontitis which is surprising as alcoholic cirrhosis is often linked to a lifestyle with poor self-care, resulting in poor oral health and increased oral infections [7, 9]. However, our finding is in accordance with others [8]. The explanation may be a consequence of the immune dysfunction that occurs progressively during the course of cirrhosis leading to an increased susceptibility to bacterial infections in the patients [29], and an increased risk of periodontitis. Another putative mechanism could be a reduced saliva flow rate. A number of factors associated with cirrhosis, such as the pharmacological management of ascites, can diminish the amount of saliva, which in turn, increases the development of plaque and favours oral infections [30, 31]. Furthermore, autoimmune hepatitis, and primary biliary cirrhosis have been associated with Sjögren’s syndrome, another cause of oral dryness [32].

Likewise, cirrhosis severity measured by the MELD score was not a predictor for severe periodontitis, although another study has reported an association between oral infections and accelerated progression of liver disease measured by the MELD score [33]. Thus, our findings indicate that it is the cirrhosis and the associated poor oral health status rather than the etiology or severity of cirrhosis which predisposes to severe periodontitis.

The results showed that smoking and brushing teeth less than twice daily were associated with severe periodontitis in the patients with cirrhosis. The importance of these factors is well known and documented in the general population [23, 34]. However, the observation that severe periodontitis was more prevalent among those visiting the dentist annually was unexpected and not explainable by our data. It may indicate either that dentists in Denmark do not treat severe periodontitis, that cirrhosis patients with severe periodontitis seek treatment more often than patients with good periodontal status, or that patients with few dental visits tend to have teeth with severe periodontitis extracted rather than treated.

The study suggested that severe periodontitis in cirrhosis patients was associated with the robust nutritional marker the nutritional risk score. This has not previously been studied in cirrhosis but is consistent with haemodialysis patients, where a relationship between malnutrition and periodontitis have been found [14, 35]. The majority of our patients suffered from severe dys-nutrition which is a massive and partly unexplained complication to cirrhosis that contributes to increased morbidity and mortality [12]. If a causal relationship between periodontitis and the degree of dys-nutrition can be established by future studies the care for cirrhosis patients should probably involve periodontal treatment. The mechanism of an effect of periodontitis on nutrition cannot be established from our data, but probably both unpleasant oral eating related experiences, such as earlier described [3], and the anorectic effect of the low grade systemic inflammation activation reported to stem from periodontitis may contribute.

CRP is a sensitive marker of systemic inflammation, and periodontitis may be associated with an increase in CRP levels [36]. Our cirrhosis cohort had increased CRP, to a large extent attributable to cirrhosis as a chronic inflammatory condition. On this platform we found only a slight stepwise increase in CRP with the severity of periodontitis but not significant. This may imply that the value of CRP for detecting systemic inflammation from periodontitis is weak in patients with cirrhosis [37].

There are limitations to this study. The study design provided only association among the study variables and not on causality. Therefore, further research must be done before the potential for oral infections to cause damage in cirrhosis patients can be definitely established. In particular, longitudinal studies with repeated oral examinations and oral interventions studies would be valuable. In addition, the findings could to some extent be due to confounding variables, such as unmeasured socioeconomic conditions, as it is shown that lower socioeconomic groups have lack of oral health awareness and dental care [38]. The possible confounding by these conditions is worth investigating in future studies. Finally, our study comprised a broad spectrum of cirrhosis patients and may be seen as representative for a cirrhosis population, but still the study design may limit generalizability of the strength of the association to other patients with cirrhosis. However, in this case, this seems unlikely as the department has a large local catchment population and also receives referred patients from other hospitals across Denmark. In addition, age, gender, cirrhosis etiology, cirrhosis severity, and comorbidities of the participating patients correspond to Danish nationwide cohort studies and other Scandinavian cohort studies performed in the recent years [39‐41]. However, we believe this study contributes with new information in the field of oral health and infections in patients with cirrhosis.

In conclusion, it was observed that periodontitis is highly prevalent in cirrhosis patients of all etiologies. Further predictors of severe periodontitis were smoking, brushing teeth less than twice daily and, unexpectedly visiting the dentist annually. Importantly, severe periodontitis was associated with a high nutritional risk score. These findings motivate further studies including interventional trials to evaluate whether improved clinical care of oral health may improve the nutritional status in patients with cirrhosis.