Impact of primary biliary cholangitis severity on oral health status

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Background

Primary biliary cholangitis (PBC) is a granulomatous, non-suppurative, destructive cholangitis that develops as a result of immune-mediated injury to the biliary epithelium of small intrahepatic bile ducts, leading to cholestasis and progressive fibrosis up to the terminal stage of biliary cirrhosis. Although PBC is considered a relatively rare disease, it nevertheless poses a significant public health challenge [1]. According to various studies, the global incidence of PBC is steadily increasing, with prevalence ranging from 1.9 to 58 cases per 100,000 population [2–4].

PBC is diagnosed predominantly in women, accounting for up to 95% of cases, most commonly between the ages of 50 and 65 years. Given global demographic trends characterized by population aging and the rising prevalence of autoimmune disorders in recent decades, there is a reasonable assumption that the frequency of PBC detection will continue to increase [5–7].

Since PBC, as well as the associated Sjögren syndrome (SS) [8–10], is accompanied by xerostomia [11], pathological changes develop in the oral cavity, leading to deterioration of oral hygiene, increased caries activity [12–13], and alterations in the oral microbiota [14–15]. Such disturbances promote the formation of chronic inflammatory foci [16], which act as factors in the progression and maintenance of the autoimmune process occurring in liver tissue, thereby negatively affecting the general condition of patients and contributing to an unfavorable disease prognosis [17].

The aim of the study was to compare the characteristics of oral cavity changes in patients with PBC with the duration, stage, and clinical features of liver disease.

Methods

A total of 48 female patients aged 43–69 years with a confirmed diagnosis of PBC, residing in St. Petersburg and the Leningrad region, and receiving outpatient treatment, were examined.

The diagnosis of PBC was established based on the presence of at least two of the three criteria recommended by the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases: elevated serum alkaline phosphatase, the presence of pathognomonic autoantibodies (antimitochondrial antibodies, antinuclear antibodies with indirect immunofluorescence patterns AC-6 and AC-12, anti-gp210, anti-sp-100), and histopathological findings [18]. All patients underwent medical history collection, physical examination, and laboratory testing, including clinical and biochemical blood analysis with the assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), albumin, bilirubin, and international normalized ratio. Liver stiffness was measured using transient elastography (FibroScan®, Echosens, France). Disease stage (early or late) was determined according to the EASL (2017) criteria, based on laboratory results and transient elastography with a threshold value of 9.6 kPa. To assess SS, the Schirmer test (tear fluid production) and sialometry according to the method of Pozharnitskaya (detection and grading of xerostomia) were performed [19].

The assessment of oral cavity status was based on clinical guidelines [20]. The following indices were assessed: the Greene–Vermillion hygiene index (OHI-S), the decayed, missing, and filled teeth index (DMFT), the papillary-marginal-alveolar index (PMA), and the sulcus bleeding index (SBI). Periodontal status was evaluated by assessing tooth mobility, probing pocket depth, and radiographic findings.

To detect DNA of major periodontopathogenic microorganisms, the Dentoscreen test system (Litekh, Russia) based on the polymerase chain reaction (PCR) was used.

Data cleaning, structuring, and analysis were carried out using the R environment (version 4.4.2). For nominal variables, mode or median values were calculated as measures of central tendency; for ratio-scale or absolute variables, the median, first quartile (LQ), third quartile (HQ), and median absolute deviation (MAD) were determined. Associations between clinical and laboratory parameters, the DMFT index, stage of periodontitis, and degree of xerostomia were analyzed taking into account the simultaneous influence of several factors, using a cumulative link model for ordinal regression (clm algorithm from the ordinal package), multiple regression (glm algorithm with Gaussian distribution), and Poisson multiple regression. The critical level of statistical significance for the null hypothesis was set at 0.05.

Results

The duration of PBC from the onset of first clinical manifestations ranged from 4 to 18 years, with a mean of 10.1 ± 3.5 years, whereas the duration from the time of diagnosis ranged from 1 to 15 years, with a mean of 7.6 ± 3.2 years. The late stage of the disease was identified in 25 patients (52.1%), of whom 8 (16.7%) were diagnosed with liver cirrhosis.

The main complaints were as follows: weakness in 41 patients (85.0%), sleep disturbances in 38 (79.0%), pruritus of varying severity in 20 (42.0%), jaundice in 5 (10.4%), and heaviness in the right hypochondrium in 8 (16.7%). Complaints of oral dryness were reported by 68.75% of patients (n = 33). Persistent xerostomia was noted in 54.17% of patients (n = 26), while episodic xerostomia was noted in 14.58% of patients (n = 7). Difficulties with mastication, gingival bleeding and halitosis were observed in 47.92% (n = 23), 60.42% (n = 29), and 45.83% (n = 22) of patients, respectively. Nine patients with PBC (18.75%) had no signs of xerostomia; early-stage, advanced-stage and late-stage xerostomia was diagnosed in 5 patients (10.42%), 24 patients (50.00%), and 10 patients (20.83%), respectively. Oral hygiene quality was rated as good, satisfactory, unsatisfactory, and poor in 28.3% (n = 13), 39.1% (n = 18), 19.6% (n = 9), and 13.0% (n = 6) of cases, respectively.

Radiological signs of periodontal disease (destruction of cortical plates and resorption of interdental septa) were observed in all patients with PBC. The distribution of periodontal pocket depth was as follows: 1–2 mm in 15.56% of cases; 3 mm in 53.33% of cases; 4–5 mm in 17.78% of cases; and 6 mm in 13.33% of cases. A PMA index was <30% in 35.56% of patients (n = 16), 31%–60% in 46.67% of patients (n = 21), and >60% in 17.78% of patients (n = 8). The Mühlemann–Cowell index ranged from 1.1 to 2.0 in 46.67% of patients (n = 21) and from 2.1 to 3.0 in 15.56% of patients (n = 7). The distribution of periodontitis stages was as follows: mild in 26.67% of patients (n = 12), moderate in 44.44% of patients (n = 20), and severe in 28.89% of patients (n = 13).

PCR testing identified DNA fragments of all major periodontopathogens: Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Fusobacterium nucleatum, and Porphyromonas endodontalis. The mean number of periodontopathogens per patient increased with advancing stage of xerostomia: 1.4 microorganisms per person at stage 0, 4.2 at stage I, 4.1 at stage II, and 5.5 at stage III.

It was established that the severity of xerostomia increased with the duration of liver disease (see Table 1).

 

Table 1. Association between xerostomia severity and duration of liver disease

Таблица 1. Зависимость тяжести ксеростомии от длительности заболевания печени

Duration of primary biliary cholangitis	No xerostomia	Early stage	Pronounced stage	Late stage	Kendall τ	p
Up to 6 years (n = 5)	2 (4.2%)	2 (4.2%)	1 (2.1%)	0 (0%)	0.51	<0.001
6–12 years (n = 30)	7 (14.6%)	2 (4.2%)	17 (35.4%)	4 (8.3%)
More than 12 years (n = 13)	0 (0%)	1 (2.1%)	6 (12.5%)	6 (12.5%)
Total (n = 48)	9	5	24	10

 

Disease duration was directly associated with liver stiffness, levels of cholestasis markers (GGT, ALP, bilirubin), and the presence of specific autoantibodies (AMA, ANA).

Comparative analysis of laboratory and instrumental data revealed a pronounced positive correlation between disease stage (liver stiffness by elastography) and the severity of xerostomia (τ = 0.54, p < 0.001), as well as with periodontitis stage (τ = 0.56, p < 0.001). In addition, a moderate positive correlation was observed between liver stiffness and the presence of SS (τ = 0.42, p < 0.001), oral hygiene status (τ = 0.49, p < 0.001), and the number of detected periodontopathogens (τ = 0.34, p = 0.002).

Positive correlations were also identified between GGT activity and the severity of xerostomia (τ = 0.45, p < .001), oral hygiene status (τ = 0.49, p < 0.001), and periodontitis stage (τ = 0.41, p < 0.001). Significant associations were found between ALT levels and oral hygiene status (τ = 0.40, p < 0.001), as well as periodontitis stage (τ = 0.41, p < 0.001).

Conclusion

The study demonstrated a direct correlation between the number of years since the onset of PBC, liver disease stage, and xerostomia stage, as well as with the increasing severity of periodontitis and worsening oral hygiene indices. The findings indicate that oral health status reflects the progression of PBC and provides an additional source of clinical information. This underscores the need for regular dental follow-up in patients with PBC and the integration of dentists into the interdisciplinary care team for such patients.

Additional info

Author contributions: A.R. Khokhlova: data curation, formal analysis, writing—original draft; N.S. Robakidze, K.L. Raykhelson, M.V. Klur: writing—review & editing. All the authors made a significant contribution to the development of the concept, research and preparation of the article, read and approved the final version before publication.

Ethics approval: The study was approved by the local ethics committee of the North-Western State University named after I.I. Mechnikov (protocol No. 4 dated 02.04.2025). All study participants signed an informed consent form before being included in the study. The study protocol was published in the journal “University Dentistry and Oral Surgery,” and the manuscript was submitted for review on 04.06.2025.

Consent for publication: The authors have obtained written informed voluntary consent from the patients to the processing and publication of personal data in a scientific journal, including its electronic version. The amount of data to be published has been agreed upon with the patients.

Funding source: The authors claim that there is no external funding when writing the article.

Disclosure of interests: The authors have no relationships, activities or interests for the last three years related with for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: When creating this work, the authors did not use previously published information (text, illustrations, or data).

Data availability statement: All data obtained in this study is available in the published article.

Generative AI: Generative AI technologies were not used for this article creation.

Acknowledgments: The authors express their gratitude to the staff of the Clinical Infectious Diseases Hospital named after S.P. Botkin (Russia, St. Petersburg), as well as to D.A. Gusev personally, for providing access to the patient’s examination.

Provenance and peer-review: This work was submitted to the journal on an initiative basis and was reviewed according to the usual procedure. Two external reviewers and the scientific editor of the publication participated in the review process.

About the authors

Anna R. Khokhlova

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: anya.davtyan@mail.ru
ORCID iD: 0009-0001-4790-7377

post-graduate student

Russian Federation, Saint Petersburg

Natalia S. Robakidze

North-Western State Medical University named after I.I. Mechnikov

Email: rona24@list.ru
ORCID iD: 0000-0003-4209-5928
SPIN-code: 6653-2182

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Saint Petersburg

Karina L. Raykhelson

Saint Petersburg State University

Email: kraikhelson@mail.ru

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Saint Petersburg

Margarita V. Klur

North-Western State Medical University named after I.I. Mechnikov

Email: Margarita.Кlur@szgmu.ru
ORCID iD: 0009-0006-6222-2452
SPIN-code: 8911-6769

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Saint Petersburg

References

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