Original Article
CLINICAL EVALUATION OF XEROSTOMIA IN PATIENTS
INFECTED WITH CHRONIC HEPATITIS C VIRUS
MARYAM ASLAM, BDS
JOHARIA AZHAR, BDS, MSc, MPhil, Fellowship in Laser Dentistry
3
EEFA TABASSUM, BDS, Research Student (MPH)
1
2
ABSTRCT
The objective of this study was to clinically evaluate the prevalence of xerostomia in chronic
hepatitis C patients. This cross sectional study observed 77 patients from December 2010 to April
2011 at the Military Hospital Rawalpindi, the Pakistan Institute of Medical Sciences Islamabad,
and the Margalla Institute of Dentistry Rawalpindi. Xerostomia was evaluated both objectively and
subjectively. Whole unstimulated salivary flow rates were measured using graduated tubes. Out of 77
patients, 40 (51.9%) were male and 37 (48.1%) were female. 70.1% patients had clinical xerostomia
based on objective and subjective evaluations. 77.9% patients had xerostomia based on sialometry.
Sialometry is a reliable tool for clinical evaluation of xerostomia. A chi-square test was used to evaluate
the association of xerostomia and treatment therapy for hepatitis. Results were statistically significant
(P<0.05). Xerostomia can be a frequent finding in patients infected with HCV so providing the adequate dental treatment for such individuals needs to be well understood by the dental professionals
as there is a significant reduction in salivary flow, which is likely to result in oral diseases.
Key Words: Hepatitis, Xerostomia, Sialometry.
INTRODUCTION
The hepatitis C virus (HCV), previously known as
one of the non-A and non-B hepatitis viruses, is a small
(38-55 nm diameter), enveloped, single – stranded, positive sense RNA virus, first isolated in 1989.1 Classified
within the Flaviviridae family, HCV is a major public
health problem and a leading cause of chronic liver
disease.2 An estimated 180 million people are infected
worldwide.3 HCV is prevalent in 1.3% of the United
States population.4 Prevalence of HCV in Pakistan is
among the highest in the world and is estimated to be
4.8% of the total population.5
Oral manifestations of hepatitis C include lichen
planus, pseudo membranous candidiasis, xerostomia,
hyposalivation and sialadenitis.6,7 Salivary gland disorders in patients with chronic hepatitis C (CHC) have
been considered oral extrahepatic manifestations, validating HCV as a sialotropic virus.8 Dry mouth without
dry eyes is the most prominent symptom of Sjogen’s
syndrome like presentation associated with Hepatitis C
disease.9 Studies have shown that there is an increased
Clinical Intern, Greenbelt, Maryland, USA
2
Consultant Oral Pathologist, Assistant Professor & Head of Oral
Pathology AIMC Abbottabad
3
Research Student (MPH) at John Hopkins University, Baltimore,
Maryland
Received for Publication:
October 16, 2014
Accepted:
October 30, 2014
1
Pakistan Oral & Dental Journal Vol 34, No. 4 (December 2014)
incidence of xerostomia in patients with HCV infection,
especially those patients on antidepressants, in addition
to the known effects of HCV on salivary glands.10
Lack of salivary flow affects a person’s quality of life
by causing difficulties in eating, swallowing, speaking,
and tasting.11 Xerostomia, the subjective feeling or
complaint of dryness in the mouth, can be caused by
several medications without actual reduction in salivary flow.12 The major cause of xerostomia, however, is
objectively assessed salivary gland hypofunction which
could be attributed to several systemic diseases such as
Sjogren’s syndrome, rheumatoid arthritis and systemic
lupus erythematosus.13,14 Salivary flow rate measurement becomes essential in diagnosing salivary gland
hypofunction as a cause of xerostomia. Salivary gland
hypofunction is considered, as whole unstimulated saliva < 0.1 mL/minute, whole chewing stimulated saliva
< 0.7 mL/minute. Accurate measurement of salivary
flow rate also is essential for various other clinical and
research purposes.15
There were two purposes of the study:
• clinically evaluate xerostomia in hepatitis C patients and
• determine the relationship of xerostomia and modality of treatment used in hepatitis C patients.
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Clinical Evaluation of Xerostomia
METHODOLOGY
This cross sectional study was carried out at the
Military Hospital, Rawalpindi, the Pakistan Institute
of Medical Sciences Islamabad, and the Margalla Institute of Dentistry, Rawalpindi between December 2010
and April 2011. 77 patients took part in the study. A
non-probability convenience sampling technique was
TABLE 1: CHARACTERISTICS OF PATIENTS
EVALUATED
Characteristics of
patients
Frequency
% of
patients
77
100.0%
Male
40
51.9%
Female
37
48.1%
Total
77
100%
3-25 years
12
15.9%
26-50 years
41
53.2%
Above 50 years
24
31.2%
Total
77
100.0%
Military Hospital (MH)
41
53.2%
Pakistan Institute of Medical
Sciences (PIMS)
19
24.7%
Margalla Institute of Health
Sciences (MIHS)
17
22.1%
Total
77
100.0%
Dental Status
Dentate
Gender
Age
Location of Study
TABLE 2: CLINICAL EVALUATION OF
XEROSTOMIA
Clinical Evaluation
of Xerostomia
Frequency
% of
patients
Subjective Xerostomia
48
62.3%
Objective Xerostomia
6
7.8%
Nil
23
29.9%
Total
77
100.0%
used to evaluate 77 patients. Only patients with confirmed diagnosis of hepatitis C made by biochemical
assessment of liver function; initial laboratory evaluation that included total and direct bilirubin; ALT; AST;
alkaline phosphatase; prothrombin time; total protein;
albumin, globulin; complete blood count; coagulation
studies; and demonstration of anti-HCV detected by
an enzyme immunoassay were included in the study.
Patients in hepatic encephalopathy, patients taking
antidepressants or other xerogenic drugs, unconscious
patients, and infants were excluded from the study.
Informed consent was taken from the patients and all
patients were willing to participate.
The patient’s biographical details including name,
age, sex, occupation, present address, weight, and
height were recorded. Past and present medical history
that included history of heart disease, tuberculosis,
diabetes mellitus, jaundice, angioplasty/angiography,
catheterization, intubation, blood transfusion, allergy,
dialysis, bleeding disorder, pregnancy, and any surgery
was recorded. Other information included medications
(antiviral drugs) or viral therapy (interferons) being
taken for the treatment of hepatitis C. History of xerogenic drugs, including alpha blockers, beta blockers,
diuretics, ACE inhibitors, calcium channel blockers, antidepressants, neuroleptics, antipsychotics, sedatives,
sympathomimetics, anticholinergics, decongestants,
antacid medications, and H2 receptor blockers, was
also recorded. The data collected were recorded on a
specially designed pro forma.
Subjective evaluation of xerostomia: A patient’s
response to a questionnaire about dry mouth and the
outcome of the clinical evaluation was used.
Objective evaluation of xerostomia: Extra
oral examination included examination of the head
and neck, lymph nodes, and major salivary glands.
Intra-oral examination included the examination of
lips for dryness and minor salivary glands located
in the buccal mucosa. The posterior hard palate was
evaluated for masses and tenderness. Oral signs that
suggest xerostomia that included new and recurrent
caries (especially on cervical margins and on incisal
edges and red fissured tongue were observed. The
classical clinical test determining xerostomia that the
oral mucosa sticks to a mouth mirror or tongue blade
when the tissue is retracted was performed.
TABLE 3: WHOLE UNSTIMULATED SALIVARY FLOW RATE/MIN
Whole Unstimulated Salivary Flow Rate/Minute
Frequency
Percent
Valid
Percent
Cumulative
Percent
Whole Unstimulated Salivary Production Greater Than 1.66 ml
17
22.1%
22.1%
22.1%
Whole Unstimulated Salivary Production Less Than 1.66 ml
60
77.9%
77.9%
100.0%
Total
77
100.0%
100.0%
Pakistan Oral & Dental Journal Vol 34, No. 4 (December 2014)
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Clinical Evaluation of Xerostomia
TABLE 4: RELATIONSHIP OF XEROSTOMIA
WITH THE TREATMENT MODALITY USED
Relationship of Xerostomia With Treatment
Modality Used
No. of
patients
Xerostomia
Interferons (IFN)
22
20
Antiviral and Interferon
Combined
16
16
No Treatment/Treatment
Finished Few Years Ago
39
18
Total
77
54
Fig 4: Clinical evaluation of xerostomia and unstimulated salivary flow rate/min cross tabulation.
Assessment of salivary flow rates: Sialometry
(measurement of salivary flow rates) was performed
using a whole unstimulated saliva production test. (Fig
1) The patient was asked to sit quietly, without talking
or chewing, and spit any saliva that accumulates in
the floor of his/her mouth into a pre-weighed tube.
This spitting test was done for a total of 5-15 minutes.
(Fig 2) However, we did not perform whole stimulated
saliva production test using candy or chewing gum.
Fig 1:Comparison of whole unstimulated saliva collected in graduated tubes with measurements.
Statistical analysis: Results were analyzed using
statistical software SPSS Version 16.0. A chi-square test
was used to evaluate categorical variables. Frequency
and percentages were calculated for variables such as
gender, age, number of patients in different hospitals,
use of xerogenic drugs, and objective and subjective
evaluation of xerostomia.
RESULTS
Fig 2: To collect the unstimulated whole saliva, patient
drools passively into the collection tube for five
minutes.
A total of 77 hepatitis C infected individuals were
assessed in this study. Table 1 shows gender, age, and
number of subjects who took part in the study in three
different hospitals. All subjects were dentate.
Clinical evaluation of xerostomia: Responses
to clinical evaluations of xerostomia were recorded as
seen in Table 2.
Salivary flow rates: Using a whole unstimulated
saliva production test, patients who had saliva production less than 1.66 mL/min were 60, or 77.9%.17 patients
(22.1%) had salivary flow rates more than 1.66 mL/min.
Patients having saliva production less than 1.66 mL/
min were considered xerostomic as seen in Table 3.
Fig 3: Age and unstimulated salivary flow rate/min
cross tabulation.
Pakistan Oral & Dental Journal Vol 34, No. 4 (December 2014)
Fig 3 shows 6 patients between age 3 to 25 years, 8
patients between 26 to 50 years, and 3 patients above
50 years had salivary flow rate greater than 1.66 mL/
min. However, 6 patients between age 3 to 25 years, 33
patients between age 26 to 50 years, and 21 patients
above 50 years had salivary flow rate less than 1.66
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Clinical Evaluation of Xerostomia
mL/min. There is a significant association between
increasing age and xerostomia (P<0.03).
Fig 4 shows that 42 patients had unstimulated salivary flow rate less than 1.66 ml/min among 48 patients
who reported xerostomia subjectively and 6 patients
had more than 1.66 mL/min flow rate among those 48
patients. 5 patients had unstimulated salivary flow
less than 1.66 mL/min among 6 patients who reported
xerostomia objectively. 17 patients showed xerostomia,
i.e. salivary flow rate less than 1.66 mL/min among
those 23 patients who exhibited no sign of xerostomia.
Relationship of xerostomia with the treatment
modality used: The response from patients undergoing
treatment was recorded as seen in Table 4.
DISCUSSION
Xerostomia is considered to be a major contributing
factor in dental and oral disease in hepatitis C patients.
There may be undetermined factors resulting from the
chronic hepatitis C viral infection itself, which contribute to the reported levels of oral disease. Although no
research has been carried out to support this concept
on humans, the transgenic mouse model proved that
xerostomia was the first clinical symptom observed in
mice infected with hepatitis C.16
In our study, prevalence of xerostomia and salivary
gland hypofunction has been investigated in patients
infected with hepatitis C. Xerostomia was prevalent
among high number of patients (62.3%). The prevalence
of "yes" responses to all questions on the dry-mouth
questionnaire was significantly higher. To determine
the hyposalivation, unstimulated whole salivary production test was performed using graduated tubes.
77.9% percent of patients had unstimulated flow rate
less than 1.66 mL/min based on sialometry.
Whole saliva is a combination of secretions produced
by the parotid, submandibular/sublingual, and minor
salivary glands. Under unstimulated conditions, the
submandibular /sublingual glands contribute about
67% and the parotid glands about 25% of whole saliva. At high levels of stimulation, parotid glands may
contribute up to 49% of whole saliva.17
Unstimulated whole saliva is predominantly produced by submandibular/sublingual glands. It is difficult to collect individual gland saliva in a multi-center
trial as ideally a modified Lashley cup or Carlson-Crittenden collector often is used for collecting saliva from
the parotid gland. Many custom-made collectors such
as the Wolff collector are used for collecting saliva
from the submandibular gland.17 Unlike some studies
in which saliva was collected from both submandibular and sublingual glands, our findings are based on
whole, not individual gland, saliva collection under an
Pakistan Oral & Dental Journal Vol 34, No. 4 (December 2014)
unstimulated condition. Our study shows a significant
correlation between the subjective evaluation of xerostomia and complaint of dry mouth and salivary gland
hypofunction based upon 42 patients that had unstimulated salivary flow rate less than 1.66 mL/min among
48 patients who reported xerostomia subjectively.
The unstimulated salivary flow rate is affected by
a variety of local, systemic, and pharmacotherapeutic
factors. Advancing age, diabetes, hypertension and
medications with anticholinergic effects, such as psychotropics and narcotics have been associated with
reduced salivary output.17 However, our study showed
the highest incidence of xerostomia among 26 years to
50 years of patients (mean age was 38 years).
Our study showed that sialometry is an effective
tool for the clinical evaluation of xerostomia. Although
our study revealed a high frequency of xerostomia in
hepatitis C patients 70.1% (P<0.01), it cannot be concluded that hepatitis C is significantly associated with
xerostomia, as it can be a symptom of Sjogren’s syndrome, which is associated with hepatitis C according
to previous studies. Interferon and ribavirin therapy
can also be one of the reasons for xerostomia in such
patients.
Studies show that approximately 12% of all HCV-infected patients receiving Peginterferon/ribavirin
therapy develop xerostomia, which in turn increases
the risk of symptoms such as dental cavities, nausea,
and constipation. A recent Italian study demonstrated
that dry mouth occurring during anti-HCV therapy
results from a reversible inhibition of salivary gland
function that does not appear to be dose dependent and
is promptly reversed upon cessation of treatment.18 In
our study regarding the relationship of xerostomia and
the modality of treatment used, out of 22 patients who
were using interferon 20 patients reported xerostomia.
16 patients who were using both antiviral and interferon therapy had xerostomia. A chi-square test was
used to analyze the association of xerostomia with the
modalities of treatment used. The results were statistically significant (P<0.05) which shows that salivary
gland hypofunction can be associated with ribavirin
and Peginterferon therapy.
CONCLUSION
Our study showed a high prevalence of xerostomia
in hepatitis C infected individuals. However, we did not
establish association between the detection of HCV,
oral health problems, and Sjogren’s syndrome. Given
the high number of hepatitis C infected individuals,
providing the adequate dental treatment for such
individuals need to be well understood by the dental
professionals as there is a significant reduction in
salivary flow, which is likely to result in oral diseases.
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Clinical Evaluation of Xerostomia
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