Hepatitis Type B and D in Oral Implications: Comparison
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Please note this is a comparison between Version 2 by Dean Liu and Version 1 by Adrian Camen.

Periodontitis is characterized by low-grade inflammation of the periodontal tissues, the structures that support and connect the teeth to the maxilla and mandible. This inflammation is caused by the accumulation of subgingival bacterial biofilm and gradually leads to the extensive damage of these tissues and the consequent loss of teeth. Hepatitis B is a major global health concern; infection with the hepatitis B virus causes significant inflammation of the liver and the possibility of its gradual evolution to cirrhosis.

  • periodontitis
  • hepatitis B
  • hepatitis D
  • pathogenesis

1. HBV Infection and Oral Implications

The study by Polloch et al. identified HBV surface antigens (HBsAg) in the GCF samples of HBV-infected patients [30][1]. In 1985, Ben-Aryeh et al. performed a similar study, which concluded that HBsAg was found in 90% of the assessed GCF samples originating from HBV-infected patients [31][2]. The surface antigen was also found in the saliva samples of the same patients. It could be speculated that the saliva might have been contaminated with the blood of gingival origin due to gingival inflammation. However, the authors found no significant correlation between the presence of HBsAg in the saliva samples and the gingival status of the participating patients in terms of gingival inflammation or the gingival bleeding index [31][2]. This led the authors to suggest that the source of HBsAg presence in the saliva samples was, in fact, the GCF [28][3]. The virus circulates in the general bloodstream, reaches the lymphatic system and eventually into the GCF due to a difference in osmotic pressure. Then it reaches the saliva, using the GCF as a carrier [32][4]. This hypothesis is also endorsed by the 1984 study by Hurlem et al., who suggested that HBV-infected patients may pose a higher risk of viral transmission in the dental office by double carriers: saliva and increased gingival bleeding when dealing with gingival inflammation [33][5].
This hypothesis is further emphasized by a more recent study by Kamimura et al., who found a strong correlation between occult blood traces in saliva and the presence of viral HBV particles [34][6]. TResearchis study ers highlighted how HBV DNA particles were found in saliva samples, particularly of elderly patients diagnosed with periodontitis [34][6]. The study further speculates that this may pose an increased risk of horizontal HBV transmission in the family, where the probability of contact with infected saliva is quite elevated [34][6]. The risk is further enhanced if patients suffer from periodontitis, with an increased gingival bleeding index [34][6]. A study by Farghaly reached similar conclusions suggesting that patients with periodontitis showed a higher proportion of hepatitis exposure and a higher detectability of salivary HBsAg [35][7]. Additional risk factors were considered to be the rural residence of patients or a medical history of past blood transfusions. Thus, the study concluded that the presence of periodontitis, severe gingival bleeding and poor oral hygiene were associated with the risk of hepatitis and the detectability of salivary hepatitis markers [35][7]. Similar results were generated in the study by Sharifian et al., who considered that the most frequent risk factors for HBV infection in studied patients were positive periodontal diagnosis and family history [36][8].
The clinical settings of unfavorable dental and periodontal diagnosis and liver damage were assessed by Yang et al., who concluded that an increased number of absent teeth were associated with an increased risk of primary liver cancer [37][9]. A study by Nagao et al. also highlighted that periodontitis might be correlated with viral liver disease [38][10]. However, the results seem inconclusive so far, as a 2011 study by Anand et al. found that the number of dental caries and the periodontal status of patients with nonalcoholic cirrhosis did not differ significantly from that of the controls without any liver disease [39][11]. Nevertheless, other oral health issues, such as halitosis, have been directly linked to HBV infection and periodontitis, including a study by Hun Han et al. [40][12]. The authors concluded that patients with periodontitis, HBV infection and neglected tongue-brushing had the highest prevalence of volatile sulphur halitosis, suggesting that liver function should be evaluated in patients dealing with bad breath [40][12].
The periodontal management of patients with an HBV infection was studied by Seshima et al., who reported a case of effective, regenerative periodontal therapy [41][13]. The patient suffered from HBV infection and diabetes mellitus, which can significantly impact the body’s healing and regenerative capabilities [41][13]. However, considering the medical history of the patient, the authors reported a clinical improvement in the periodontal parameters [41][13]. A study by Ting et al. suggested the use of statins as an adjunctive to periodontal therapy in patients with an HBV infection [42][14]. This is justified by the antiviral properties of statins, as well as their antibacterial capabilities, including on important periodontal pathogens such as Porphyromonas gingivalis [42][14]. Concerning the surgical management of periodontal patients with an HBV infection, Hong et al. reported no episodes of postoperative bleeding in patients, despite a significant correlation of the international normalized ration (INR) with HBV infection diagnosis [43][15]. The authors suggested that it was not only INR values that should be considered when evaluating patients with liver diseases for procedures with a post-surgical bleeding risk [43][15].
From an immunological perspective, certain inflammation mediators were targeted in the saliva samples of patients with an HBV infection [44][16]. Pro-inflammatory interleukins (IL-2 and IL-4), as well as anti-inflammatory ones (IL-10), expressed significantly more elevated levels in the saliva samples of HBV infected patients than in the healthy controls, as depicted by the enzyme-linked immunosorbent assay (ELISA) used in this study [44] [16]. The same immunological method (ELISA) was proposed in the study by Gharavi et al. as a diagnosis tool for HBV infection in samples of saliva, with good sensitivity and specificity [45][17].

2. HDV Infection and Oral Implications

In a 1986 article, Cottone et al. raised awareness among dental practitioners and members of the dental office team of the possibility of the transmission of the newly identified, at that time, HDV virus [46][18]. The authors stated that the hepatitis D virus could pose a serious threat to all members of the dental team and thus encouraged vaccination against the HBV virus, as it would also offer protection against HDV [46][18].
One of the main reasons why the literature on the oral implications of HDV is limited, is that the viral infection is mainly conditioned by a co-existing or pre-existing infection with HBV. Hence, the patient target group is limited only to HBV-positive persons. Even though the association of the HBV and HDV viruses is generally accepted and agreed upon, some authors have reported exceptions to this. In 2016, Weller et al. detected HDV in the salivary glands of Sjogren syndrome patients [47][19]. Their micro-array analysis showed that HDV was present in more than 50% of the samples originating from primary Sjogren syndrome patients [47][19]. The novelty of the study was the fact that the identification of HDV was independent of any HBV presence. This suggests that HDV is able to set up an independent presence without HBV, at least at the salivary gland level, and exhibits a unique tissue tropism [47][19]. The results of this study  raise significant awareness from an oral health perspective, as Sjogren syndrome is considered to be a major trigger for dental and periodontal problems, as well as an extra-hepatic manifestation of liver diseases, including viral infections.
Currently, there is insufficient data on whether HDV particles could be carried by saliva, similar to HBV. Only one study, performed by Isaeva et al., focused on this topic but found no detection of HDV antibodies in saliva samples originating from patients with HBV and HDV infection [48][20]. Despite the fact that the saliva samples were positive for HBV antigens and antibodies, this was not the case for HDV, suggesting a lower concentration of these elements in the saliva than for HBV [48][20]. Nevertheless, the matter should be addressed by complementary research in order to increase its scientific understanding.

References

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  2. Ben-Aryeh, H.; Ur, I.; Ben-Porath, E. The relationship between antigenaemia and excretion of hepatitis B surface antigen in human whole saliva and in gingival crevicular fluid. Arch. Oral Biol. 1985, 30, 97–99.
  3. Gheorghe, D.N.; Camen, A.; Popescu, D.M.; Sincar, C.; Pitru, A.; Ionele, C.M.; Nicolae, F.M.; Danilescu, C.M.; Roman, A.; Florescu, C. Periodontitis, Metabolic and Gastrointestinal Tract Diseases: Current Perspectives on Possible Pathogenic Connections. J. Pers. Med. 2022, 12, 341.
  4. Lamster, I.; Ahlo, J. Analysis of Gingival Crevicular Fluid as Applied to the Diagnosis of Oral and Systemic Diseases. Ann. N. Y. Acad. Sci. 2007, 1098, 216–229.
  5. Hurlen, B.; Jacobsen, N.; Hurlen, P. Hepatitis B serum markers and oral health in a group of Norwegian male prisoners. Acta Odontol. Scand. 1984, 42, 53–58.
  6. Kamimura, H.; Watanabe, J.; Sugano, T.; Kohisa, J.; Abe, H.; Kamimura, K.; Tsuchiya, A.; Takamura, M.; Okoshi, S.; Tanabe, Y.; et al. Relationship between detection of hepatitis B virus in saliva and periodontal disease in hepatitis B virus carriers in Japan. J. Infect. Chemother. 2021, 27, 492–496.
  7. Farghaly, A.G.; Mansour, G.A.; Mahdy, N.H.; Yousri, A. Hepatitis B and C virus infections among patients with gingivitis and adult periodontitis: Seroprevalence and public health importance. J. Egypt. Public Health Assoc. 1998, 73, 707–735.
  8. Sharifian, A.; Ashtari, S.; Hatami, B.; Mohebbi, S.R.; Naderi, N. Risk factors of transmission and natural history of chronic hepatitis B infection in Iranian patients. Gastroenterol. Hepatol. Bed Bench 2019, 12 (Suppl. 1), S149–S155.
  9. Yang, B.; Petrick, J.; Abnet, C.; Graubard, B.; Murphy, G.; Weinstein, S.; Männistö, S.; Albanes, D.; McGlynn, K. Tooth loss and liver cancer incidence in a Finnish cohort. Cancer Causes Control 2017, 28, 899–904.
  10. Nagao, Y.; Kawahigashi, Y.; Sata, M. Association of Periodontal Diseases and Liver Fibrosis in Patients with HCV and/or HBV infection. Hepat. Mon. 2014, 14, e23264.
  11. Anand, A.; Pardal, P.; Sachdev, V. Dental caries and periodontal disorders in chronic liver disease. Med. J. Armed Forces India 2001, 57, 26–30.
  12. Han, D.; Lee, S.; Lee, J.; Kim, Y.; Kim, J. Association between viral hepatitis B infection and halitosis. Acta Odontol. Scand. 2013, 72, 274–282.
  13. Seshima, F.; Nishina, M.; Namba, T.; Saito, A. Periodontal Regenerative Therapy in Patient with Chronic Periodontitis and Type 2 Diabetes Mellitus: A Case Report. Bull. Tokyo Dent. Coll. 2016, 57, 97–104.
  14. Ting, M.; Whitaker, E.; Albandar, J. Systematic review of the in vitro effects of statins on oral and perioral microorganisms. Eur. J. Oral. Sci. 2015, 124, 4–10.
  15. Hong, C.; Scobey, M.; Napenas, J.; Brennan, M.; Lockhart, P. Dental postoperative bleeding complications in patients with suspected and documented liver disease. Oral Dis. 2012, 18, 661–666.
  16. Azatyan, V.; Yessayan, L.; Shmavonyan, M.; Melik-Andreasyan, G.; Perikhanyan, A.; Porkshenyan, K. Evaluation of IL-2, IL-10, IL-4 and γ-interferon levels in the oral fluids of patients with hepatitis C, B and HIV. J. Infect. Dev. Ctries. 2019, 13, 069S–074S.
  17. Gharavi, M.; Esmaeili, M. Evaluation of HBs-Ag and anti-HBc levels in serum and saliva of patients with hepatitis B. Med. J. Islam. Repub. Iran 2020, 34, 101.
  18. Cottone, J. Delta hepatitis: Another concern for dentistry. J. Am. Dent. Assoc. 1986, 112, 47–49.
  19. Weller, M.; Gardener, M.; Bogus, Z.; Smith, M.; Astorri, E.; Michael, D.; Michael, D.; Zheng, C.; Burbelo, P.; Lai, Z.; et al. Hepatitis Delta Virus Detected in Salivary Glands of Sjögren’s Syndrome Patients and Recapitulates a Sjögren’s Syndrome-Like Phenotype in Vivo. Pathog. Immun. 2016, 1, 12.
  20. Isaeva, O.; Ilchenko, L.; Kichatova, V.; Potemkin, I.; Amon, E.; Saryglar, A.; Al-Sharabi, S.; Kyuregyan, K.; Mikhailov, M. Detection of markers of hepatitis b and d virus infection in biological media and dried blood spots. Klin. Lab. Diagn. 2020, 65, 95–99.
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