Background
In Japan, hepatocellular carcinoma (HCC) is the fourth leading cause of death in males and the sixth in females according to a recent survey. The incidence of HCC has increased in Japan throughout the past several decades [
1]. Hepatitis C virus (HCV) is the major cause of HCC in Japan, with 70% of cases being HCV-related. It is assumed that between one and two million Japanese people are chronically infected with HCV [
1].
Interferon (IFN) therapy for chronic hepatitis C is the only treatment for completely eliminating the virus. Combination therapy with pegylated IFN (Peg-IFN) and ribavirin has been recommended widely as the first choice for chronic hepatitis C patients with high viral loads. The sustained virological response (SVR) rate after 48 weeks of treatment at a standard dose is approximately 40 to 50% [
2‐
5]. It has been shown that IFN therapy decreases the rate of development of HCC and improves the long-term prognosis [
6‐
9].
Although IFN therapy has therapeutic benefits, the treatment produces a number of well-described side effects that are dominated by fatigue, influenza-like syndrome and neuropsychiatric symptoms [
2‐
5,
10‐
12] and management of such side effects is required during therapy. Among the side effects in a Japanese Phase III trial of Peg-IFN alfa-2a/alfa-2b and ribavirin, dental problems have been documented in patients with chronic hepatitis C. Meanwhile, it has been reported that hepatitis C infected patients have significant oral health needs [
13‐
16] and that experience of dental caries is significantly worse for HCV-infected patients than patients in general [
13].
Therefore, in the present study, we determined whether dental problems delayed the initiation of IFN therapy for HCV-infected patients.
Discussion
The results indicate that oral health care may be required before HCV-infected patients undergo IFN therapy. In our study, dental problems delayed the initiation of IFN therapy for a maximum of 105 days. HCV-infected patients treated with IFN therapy should be managed by intensive oral care because of lower resistance to infection during the therapy.
Poor of oral health has been reported for HCV-infected patients [
13‐
16]. Coates et al. reported that the dental caries experience of HCV-infected subjects was significantly worse than that of patients in general, that the number of teeth missing from patients with hepatitis C infection also was significantly higher than for patients in general, and that periodontal health tended to be poor [
13]. Griffin et al. found that patients with rheumatoid arthritis, diabetes or a liver condition were twice as likely to have an urgent need for dental treatment as patients who did not have these diseases and documented a high burden of unmet dental care needs among patients with chronic diseases [
16]. The authors showed that HCV was the strongest predictor of patients reporting poor oral health.
Japanese HCV-infected patients tend to be older than those in other countries and their older age favors the onset of HCC, leading to an increased mortality rate [
1]. Peg-IFN-ribavirin combination therapy is the standard treatment for chronic hepatitis C. Meanwhile, the frequency of adverse events in combination therapy is relatively high (20-64%) [
2‐
5,
10‐
12].
In a Japanese Phase III trial of Peg-IFN alfa-2a and ribavirin involving 199 patients with chronic hepatitis C, including 99 patients with IFN treatment-naive genotype 1 and 100 patients with patients whom had not had a SVR after IFN therapy, the oral side effects were: gingival bleeding and gingival swelling (6%), toothache (4.5%), gingivitis and periodontitis (3%), dental caries (1.5%), stomatitis and cheilitis (19.1%), disorder of taste (15.6%), dry mouth (6.5%), glossalgia and glossitis (4.5%), perioral paresthesia (2.5%), oral pain (0.5%), oral mucosal damage (0.5%), oral lichen planus (0.5%), oral hemorrhage (0.5%), dry lip (0.5%), and bulla of lip (0.5%). On the other hand, in a Japanese Phase III trial of Peg-IFN alfa-2b and ribavirin involving 332 chronic hepatitis C patients, including 269 patients for 48 weeks treatment duration with genotype 1b and high virus load, and 63 patients for 24 weeks treatment duration with others, oral side effect were: dental pulpitis, gingivitis, and periodontitis (8.9%), toothache (7.1%), dental abnormity (1.1%), stomatitis and cheilitis (26.8%), disorder of taste (26.8%), dry mouth (15.6%), glossitis (5.9%), oral discomfort feeling (2.6%), oral hemorrhage (0.4%), oral pain (0.4%), dry tongue (0.4%), decreased secretion of saliva (0.4%).
These findings indicate that dental management of HCV-infected patients is required before IFN therapy. However, in Japan the importance of oral health is often overlooked in HCV-infected patients and has not been discussed in detail up to now.
Several studies have shown an association between HCV and sicca symptoms [
20,
21]. Patients with chronic HCV infection also have been reported to be at a greater risk of developing insulin resistance [
22,
23]. Severe periodontal disease causes insulin resistance [
24]. The reasons that HCV-infected individuals had problems such as dental caries and oral health care may include a decreased salivary flow rate, elicitation of periodontal disease by insulin resistance and difficulties for radical dental treatment of patients with liver disease who may have problems such as prolonged bleeding.
Henderson et al. reported HCV-infected cases and suggested the possibility of occasional discrimination by practitioners. They concluded that more effective oral health education is required for HCV-infected patients and dental practitioners [
15]. We distributed a questionnaire to 209 patients who visited our hospital for liver disease treatment to determine whether patients with HCV or hepatitis B virus (HBV) disclosed their disease status to the personnel in dental clinics. We found that 59.8% always did so, 12.0% sometimes did so and 28.2% never did so. The main reason for nondisclosure was failure of dental healthcare workers to ask whether patients had systemic disease. Other reasons included fear of negative reactions from healthcare workers and not wanting dentists or staff to know their specific liver ailment [
25]. To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to create cooperation.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
YN carried out most of the data collection and drafted the manuscript. MS contributed to data analysis. All authors read and approved the final manuscript.