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Hepatitis C Virus and Dental Health Workers:

An Update

Article in Oral health & preventive dentistry · June 2014

Impact Factor: 0.51 · DOI: 10.3290/j.ohpd.a32134 · Source: PubMed

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Garbin
ARTICLE
et al

Hepatitis C Virus and Dental Health Workers:

An Update

Cléa Adas Saliba Garbina/Neila Paula de Souzab/Romes Rufino de Vasconcelosc/

Artênio José Isper Garbind/Lívia Melo Villare

Summary: Hepatitis C virus (HCV) infection is a worldwide health problem, affecting over 130 million individuals. The
virus is transmitted parenterally, making health care professionals a risk group for infection. For this reason it is im-
portant that dental health-care workers recognise the symptoms of the infection, which can be present in the oral
cavities of hepatitis C-infected individuals. Moreover, dental health-care workers should know how to manage hepatitis
C-infected individuals during dental treatment and the measures to prevent nosocomial spread of HCV. Thus, the pur-
pose of this study was to perform a review of HCV epidemiology, natural history, transmission, diagnosis, treatment
and prevention focusing on oral manifestations in and dental management strategies for HCV-infected individuals.

Key words: hepatitis C virus, dentistry, dental health workers, oral health

doi: 10.3290/j.ohpd.a32134 Submitted for publication: 12.12.12; accepted for publication: 14.03.13

I n the 1970s, researchers observed that most cas-

es of post-transfusion hepatitis were not attribut-
able to either hepatitis A or hepatitis B viral infec-
EPIDEMIOLOGY

HCV infection presents a global prevalence around

tion, thus identifying a new disease termed ‘non-A,
non-B’ (NANB) hepatitis (Feinstone et al, 1975). In
1989, Choo et al isolated complementary DNA of
the hepatitis C virus (HCV); subsequent retrospec-
tive testing of stored serum samples from these
studies confirmed that HCV infection accounted for
most parenteral NANB hepatitis regardless of the
setting in which transmission occurred (Alter et al,
1989; Kuo et al, 1989; Choo et al, 1990; Alter et
al, 1992; Seeff et al, 1992).
a
Adjunct Professor and Coordinator of Preventive and Social Den-
tistry Postgraduate Programme, Universidade Estadual Paulista
(UNESP), Araçatuba, SP, Brazil.
b
Master’s Degree Candidate, Preventive and Social Dentistry Post-
graduate Programme, Universidade Estadual Paulista (UNESP),
Araçatuba, SP, Brazil.
c
Adjunct Professor, Graduate Course in Medicine, Universidade
Presidente Antônio Carlos (UNIPAC), Uberlândia, MG, Brazil.
d
Assistant Professor, Preventive and Social Dentistry Postgradu-
ate Programme, Universidade Estadual Paulista (UNESP), Araça-
tuba, SP, Brazil.
e
Technologist, Viral Hepatitis Laboratory, Oswaldo Cruz Institute
(FIOCRUZ), Rio de Janeiro, RJ, Brazil.
Correspondence: Neila Paula de Souza, Universidade Estadual
Paulista (UNESP), Faculdade de Odontologia de Araçatuba, Progra-
ma de Pós-graduação em Odontologia Preventiva e Social; NE-
PESCO, Departamento de Odontologia Infantil e Social, Rua José
Bonifácio, 1193 – Caixa Postal 341, CEP 16015-050 Araçatuba, SP,
Brazil. Tel: +55-018-3636-3250, Fax: +55-018-3624-4890. Email:
neilapsouza@hotmail.com
2% to 3%, i.e. between 123 million and 170 million
people worldwide are infected with HCV (Yen et al,
2003; Shepard et al, 2005; Sy and Jamal, 2006;
Alter, 2007; Lavanchy, 2011). Every year, 3 to 4 mil-
lion people are infected with the hepatitis C virus
(HCV) and more than 350,000 die each year from
complications of the disease (WHO, 2012).
Although hepatitis C is endemic worldwide, dif-
ferent prevalence rates of HCV infection are ob-
served around the world (Shepard et al, 2005; Ker-
shenobich et al, 2011; Martins et al, 2011).
Anti-HCV prevalence (prevalence of antibodies
against HCV) is higher in the Middle East (4.7%)
and Africa (3.2%), followed by Europe (2.3%) and
Asia (2.1%) (Lavanchy, 2011). Egypt has a high
prevalence of HCV infection (17% to 26%) (Perz et
al, 2004; Shepard et al, 2005). Otherwise, low
rates of HCV infection have been observed in Amer-
ica (1.5%) and Australia (1.2%) (Lavanchy, 2011).
A recent review has shown that HCV prevalence
ranges from 1.4% to 2.5% in the adult population
from Latin America (Kershenobich et al, 2011). In
Brazil, a population-based study showed 1.38% of
anti-HCV prevalence across the country (Brasil,
2012), but a survey conducted among blood do-
nors from 5 geographical regions showed higher
prevalence in the northern region (2.12%), low
prevalence in the southern region (0.65%) and an

doi: 10.3290/j.ohpd.a32134 1
Garbin et al

Exposure to HCV

1–2 weeks

Infection with HCV No infection with HCV

Acute hepatitis C
(25% symptomatic, 75% asymptomatic)
0 to 20 years of disease evolution

Chronic hepatitis C Infection clears

(60–85%) (15–40%)

Spontaneous elimination of HCV Absence of fibrosis and Presence of fibrosis

(0.50–0.74%) inflammation and inflammation

Cirrhosis
(20%)

Uncompensated cirrhosis Hepatocellular carcinoma

(4%) (1.6%)

Death Liver transplant Death

(industrialised countries,15%; (industrialised countries, 80%;
developing countries, 30%) developing countries, 90%)

Fig 1  Natural course of hepatitis C (Alter et al, 1992; Fattovich et al, 1997; Serfaty et al, 1998; El-Serag et al, 2001; Jauncey
et al, 2004; The Global Burden of Hepatitis C Working Group, 2004; Scott et al, 2006).

intermediate prevalence midwestern, northeastern
and southeastern regions (1.04%, 1.19%, and
1.43%, respectively) (SBH, 1999). Different HCV
prevalences were observed among dentists world-
wide, varying from 0.4% to 0.9% in Brazil (Takaha-
ma et al, 2005; Resende et al, 2009), 0.33% in
Israel (Ashkenazi et al, 2009), 0.5% in Germany
(Ammon et al, 2000) and 1.75% in the USA (Klein
et al, 1991).
Natural History
HCV possesses a positive-sense single-strand ge-
nome and is classified in the Flaviviridae family,
Hepacivirus genus. Hepatitis C virus is classified
into six genotypes (1–6), each of which has related
subtypes (Simmonds et al, 2005). Genotypes 1–3
have a worldwide distribution, genotypes 4 and 5
are found principally in the Middle East and Africa
and genotype 6 is distributed across Asia (Ashfaq
et al, 2011).
The incubation period for acute HCV infection is
1 to 3 weeks. Within an average of 4 to 12 weeks,
HCV RNA can be detected in blood and corresponds
to the onset of symptoms and elevated serum ALT
levels. Most of HCV infected individuals (60%–70%)
are asymptomatic (The Global Burden of Hepatitis
C Working Group, 2004), so a high percentage of
them only recognise that they are infected when a
chronic state is reached, presenting elevated risk
of cirrhosis, hepatocellular carcinoma and death
(Alter et al, 1992). The natural history of HCV infec-
tion is presented in Fig 1.

2 Oral Health & Preventive Dentistry


Only 20%–30% of cases present symptoms,
such as: abdominal, muscular, or joint pain; fa-
tigue; anorexia; fever; nausea; jaundice; dark urine
and pale feces. A physical exam can show an in-
crease in the size and a change in the consistency
of the liver as well as splenomegaly (Wilkins et al,
2010). Extra-hepatic manifestations of HCV infec-
tion have been observed, for instance, significant
association between HCV and the following diseas-
es are supported by sufficient data: mixed cryoglo-
bulinemia, B-cell-derived non-Hodgkin’s lymphoma
(NHL), diabetes mellitus, porphyria cutanea tarda
and lichen planus. Other manifestations still re-
quire confirmation and a more detailed characteri-
sation with respect to similar pathologies of differ-
ent aetiology or idiopathic nature: idiopathic
pulmonary fibrosis, autoimmune thyroiditis, sicca
syndrome, noncryoglobulinaemic nephropathies
and glomerulonephritis as well as aortic athero-
sclerosis (Khattab et al, 2010). As the disease
evolves, liver failure and portal hypertension can
occur, including ascites, haemorrhage from gastric
and esophageal veins and hepatic encephalopathy.
HCV infection is the most common reason for a
liver transplant (Nayak et al, 2012).
Transmission
HCV is mainly transmitted parenterally via large or
repeated exposure to contaminated blood or
haemoderivative products, such as occur in blood
transfusion or organ, tissue and bone marrow
transplants from HCV infected donors, as well as
the use of injected drugs. Other less common and
less effective mode of HCV transmission include
small-dose percutaneous exposure with contami-
nated blood (i.e. accidents with needles or sharp
objects) or by exposure of mucosa to blood or
haemoderivative products, such as during child-
birth or unprotected sex with HCV-infected partners
(CDC, 1998). Thus, individuals at high risk for HCV
infection are those who received blood transfu-
sions or haemoderivatives before 1992, when anti-
HCV tests were not mandatory at blood banks, pa-
tients on haemodialysis, haemophiliacs, prisoners,
the sexually promiscuous, transplant recipients,
people with tattoos and piercings and illicit intrave-
nous drug users (CDC, 1998; Jafari et al, 2010).
There are several reports of health-care workers
who contracted HCV infection after needle-stick in-
jury (Vaglia et al, 1990; Seeff et al, 1992; Tsude et
al, 1992). Transmission of HCV from health-care
doi: 10.3290/j.ohpd.a32134
Garbin et al
workers to patients is rare, although in one case,
an HCV-positive cardiac surgeon transmitted HCV
to five patients during open heart surgery (Esteban
et al, 1996).
Other possible mechanisms for HCV transmis-
sion have been discussed, such as barber and acu-
puncture services, scarification rituals and circum-
cision (Lock et al, 2006; Waheed et al, 2011).
Furthermore, since HCV can remain infectious after
drying and exposure to air at room temperature for
at least 16 hours, the role of inanimate surfaces,
objects, and/or appliances as fomites for HCV has
been discussed (Kamili et al, 2007). Thus, dental
patients and dental health-care workers need to be
equipped with adequate knowledge about cross-
infection control and education reinforcement is
imperative (Barghout et al, 2012).
DIAGNOSIS
HCV diagnosis is based on the detection of anti-
HCV antibodies by third generation ELISA assays.
These assays can detect anti-HCV antibodies on
average 2–8 weeks after the acute phase of infec-
tion and persist for life in patients who develop
chronic HCV infection (Chevaliez, 2011).
Assays to detect HCV core antigen demonstrat-
ed a significant relationship to the HCV RNA level
measured by means of a molecular biology tech-
nique, but these assays are not as sensitive as
molecular assays (Bouvier-Alias et al, 2002; Park
et al, 2010). Simultaneous detection of anti-HCV
antibodies and HCV core antigen have been devel-
oped as HCV combination assays that detect acute
HCV infection on average 20 days before third-gen-
eration antibody-only assays, but they are less sen-
sitive than third-generation anti-HCV assays for an-
tibody detection and detect HCV infection later
than HCV RNA assays (Laperche et al, 2005).
In order to identify active infection (HCV RNA de-
tected) or recovery (HCV RNA not detected), anti-
HCV reactive serum samples should be submitted
to molecular assays. The HCV RNA can be detected
1–3 weeks after infection, approximately 1 month
before the appearance of total anti-HCV antibod-
ies, and its presence after 6 months denotes
chronic HCV infection. HCV RNA detection and
quantification are useful to diagnose chronic HCV
infection, recognise individuals who need antiviral
therapy, monitor the virological responses to antivi-
ral therapy and document treatment failure (Pawlot-
sky, 2002).
3
Garbin et al
TREATMENT AND PREVENTION
The current standard treatment for chronic hepati-
tis C infection is the combination of pegylated IFN-
a2a or IFN-a2b and ribavirin (NIH, 2002). The future
standard treatment of chronic genotype-1 hepatitis
C will be the triple combination of pegylated IFN-
a2a or IFN-a2b, ribavirin and a protease inhibitor,
boceprevir or telaprevir. The efficacy endpoint of
chronic hepatitis C treatment is the sustained viro-
logical response (SVR), defined as an undetectable
HCV RNA load in serum with a sensitive assay (low-
er limit of detection of 10–15 IU/ml) 24 weeks after
the end of treatment (Chevaliez, 2011).
The duration of treatment, dose of ribavirin, viro-
logical monitoring procedure and rate of SVR de-
pends on HCV genotype. Individuals infected with
genotypes 1, 4, 5 and 6 receive 1000–1400 mg
daily, treatment duration is 48 weeks and SVR is
achieved in 40%–50% of treated patients. Individu-
als infected with HCV genotypes 2 and 3 receive a
low dose of ribavirin, i.e. 800 mg daily, and require
24 weeks of treatment to induce SVR in ≥80% (Di-
ago et al, 2010). Before initiating treatment, the
stage of liver disease, general state of health and
contraindications for the use of the drugs to be ad-
ministered should be evaluated (Hadziyannis et al,
2004).
The aims of HCV treatment are to alleviate liver
fibrosis, reduce transaminase levels, prevent hepa-
tocellular carcinoma, improve the patient’s quality
of life and knock down the HCV viral load, helping
to prevent the dissemination of the disease by re-
ducing the number of people who can transmit it
(Pearlman and Traub, 2011). Before HCV treat-
ment, it is recommended that the oral health of the
patients be evaluated. If oral diseases such as
periodontitis and pulpitis are present, the begin-
ning of HCV treatment should be discussed by an
interdisciplinary team and can be postponed for up
to 105 days. During HCV therapy, attention to oral
health needs to be intensified, as there is a re-
duced resistance to infection (Nagao and Sata,
2010).
In order to prevent HCV infection, the develop-
ment of health education programmes is recom-
mended, as is identifying HCV infected individuals
in high risk groups. Dental health-care workers can
contribute to preventing HCV infection by using ad-
equate biosecurity during dental procedures. The
general public should also be informed about not
sharing syringes and/or needles, pipes or straws
when using drugs, as well as not sharing razors for
4 Oral Health & Preventive Dentistry
Table 1 Oral diseases that may occur in patient with
hepatitis C
Mucocutaneous diseases
Behcet’s disease Leukoplakia
Candidiasis Lichen planus
Epidermoid carcinoma Lupus erythematosus
Erythema multiforme Mouth ulcers
Changes to the oral cavity
Chronic cheek biting Hemorrhagic disorders
Salivary glands
Sialadentitis Hyposalivation
Sjögren’s Syndrome Xerostomy
Tongue
Soft atrophic cheilitis Palate disorder
Foetor hepaticus Mucous membrane ictericia
(Lodi et al, 1998; Figueiredo et al, 2002; Golla et al, 2004; Nagao
and Sata M, 2010; Scully and Felix, 2010; Carr et al, 2012).
shaving and hair removal, manicure/pedicure in-
struments, tattooing and piercing instruments and
acupuncture materials. In addition, they should
also be encouraged to use condoms for all sexual
practices (CDC, 1998).
Currently, there is no preventive vaccine for hep-
atitis C due to various obstacles, such as: high ge-
netic and antigenic diversity, with at least six differ-
ent HCV genotypes and many quasispecies within
the same infected individual; a lack of small animal
models; the inability to produce large quantities of
HCV in tissue culture (Bukh, 2012). Potential HCV
vaccine candidates include recombinant viruses or
bacteria, DNA plasmids, synthetic peptides and vi-
rus-like particles (Feinstone et al, 2012).
ORAL HEALTH AND MANAGEMENT AMONG
HCV-POSITIVE INDIVIDUALS
Up to 74% of patients infected with HCV can devel-
op at least one extra-hepatic manifestation during
the course of the disease (Galossi et al, 2007) and
some of these manifestations can cause oral prob-
lems and/or indicate the need for special care
when performing dental interventions. The oral cav-
ity can exhibit signs of liver problems in the form of
various disorders and diseases (Table 1).

Among extrahepatic manifestations of HCV in-
fection involving the oral region, lichen planus and
Sjögren’s syndrome (SS) are the most discussed.
HCV-infected patients may frequently present his-
tological signs of Sjögren-like sialadenitis with mild
or even absent clinical symptoms or lichen planus
(Carr et al, 2007; Galossi  et al, 2007; Konidena
and Pavani, 2012). Several studies show that HCV
markers are present in saliva (Amado et al, 2006;
Caldeira et al, 2012; Cruz et al, 2012), although
how this may impact Sjögren’s syndrome or the re-
lated sicca syndrome in HCV is unclear. It is un-
clear whether the virus may cause a disease mim-
icking primary SS or if HCV is directly responsible
for the development of SS in a specific subset of
patients. In addition, HCV may be involved in lym-
phomagenesis, particularly among individuals pre-
senting mixed cryoglobulinemia (Carrozzo, 2008).
A recent study among HCV patients in Brazil
showed that 96.3% of them presented oral mu-
cosal conditions, such as oral mucosal lesions and
oral lichen planus (Grossmann et al, 2009). Thus,
HCV patients should be given special care during
dental treatment. Dental care for hepatitis C pa-
tient starts with a thorough direct case history,
which should include the patient’s identification
data, his/her sociodemographic and psychosocial
profile and a detailed record of the patient’s prior
and current medical and dental history. The impor-
tance of asking patients about their use of medica-
tions must be emphasised. In addition to obtaining
a well-performed medical history, the dentist needs
to work with an interdisciplinary team to under-
stand the liver damage of the patients and their
general state of health. The objectives of dental
care in HCV patients are to evaluate their suscepti-
bility to infection and haemorrhage, the possibility
of adverse reactions to dental treatment and their
ability to tolerate stress during treatment, where
the final goal is the development of a safe treat-
ment plan (Hong et al, 2012).
HCV-infected individuals, even in the chronic
stage of disease or in liver transplant candidates,
can be submitted to dental care if necessary, e.g.
removal of decayed tissue and restoration of cari-
ous lesions, basic periodontal treatments, adjust-
ment of prostheses, tooth extraction and endodon-
tic treatments (Dougall and Fiske J, 2008; Nagao
and Sata, 2010). Preventive and educational den-
tal procedures, such as orientation about oral hy-
giene and diet, supragingival prophylaxis and the
topical use of fluoride should be performed inde-
pendent of the stage of liver disease. HCV-infected
doi: 10.3290/j.ohpd.a32134
Garbin et al
individuals present a high risk of caries and perio-
dontal disease due to decreased salivary flow (hy-
posalivation) in the former (Scully and Felix, 2005)
and poor bucal hygiene, insulin resistance or pro-
longed bleeding in the latter (Nagao and Sata,
2010).
Before performing invasive procedures such as
tooth extraction, periodontal surgery and the ad-
ministration of local anaesthetic, dental surgeons
should order blood tests, such as platelet count
prothrombin time/INR (international normalised ra-
tios) and activated partial thromboplastin time,
since HCV patients are at high risk of developing
severe haemorrhage (Golla et al, 2004; Hong et al,
2012). In addition, HCV patient’s primary care phy-
sician should be consulted if there are some doubts
about the patient’s general health and possible
risks for dental treatment (Dougall and Fiske,
2008).
In order to minimise possible trauma during inva-
sive dental procedures, dental surgeons can use
local anaesthetics with a vasoconstrictor or hae-
mostatic agent in cavities (oxidised cellulose or col-
lagen sponges) to avoid haemorrage. They can also
use removable sutures with precision to avoid the
trauma associated with suture removal and give
post-operative advice to patients. The dental sur-
geon should also advise patients on post-operative
care and measures to prevent post-operative com-
plications; in addition, the dental surgeon should
not not prescribe or administer potentially hepato-
toxic drugs (Dougall and Fiske, 2008).
OCCUPATIONAL RISK FOR DENTAL HEALTH
WORKERS
Dental health workers are at biological risk due to
occupational exposure to blood through sharp in-
struments. Every year, approximately 3 million
health professionals (about 10% of this job cat-
egory) report some percutaneous exposure world-
wide, and it is estimated that these accidents re-
sult in 15,000 hepatitis C infections per year (WHO,
2012).
Since HCV is most efficiently transmitted through
percutaneous exposures to blood, there is a poten-
tial risk for dental health workers during their oc-
cupational activities; it was observed that dental
students are frequently exposed to needle-stick ac-
cidents (Silva et al, 2009). However, follow-up stud-
ies of health care workers exposed to HCV-infected
blood through percutaneous or other sharp-instru-
5
Garbin et al

Exposure to HCV

Alanine aminotransferase Anti-HCV

Normal Elevated Positive Negative

Repeat at 1, 3, and 6 months Hepatopathy Repeat at 1, 3, and 6 months

Normal Elevated
HCV- RNA Positive Negative

No disease
Positive Negative

Active disease Inactive Disease

Treatment

Fig 2  Diagnostic algorithm after hepatitis C exposure (CDC, 2001; Brasil, 2006).

ment injuries found that the incidence of anti-HCV
seroconversion averaged 1.8% (range 0% to 7%)
(Klein et al, 1991; Thomas et al, 1996). In addition,
the prevalence of hepatitis C among dental health
workers is similar to the general population (SBH,
1999; Ammon et al, 2000; Weber et al, 2001;
Takahama et al, 2005; Ashkenazi et al, 2009; Re-
sende et al, 2009).
In case of blood exposure, dental health workers
should adopt the following measures according to
exposure type (CDC, 2001):
• Cutaneous or percutaneous injuries: the affect-
ed area should be washed very carefully with wa-
ter and soap. No evidence exists that using anti-
septics for wound care or expressing fluid by
squeezing the wound further reduces the risk of
blood-borne pathogen transmission; however,
the use of antiseptics is not contraindicated.
• Mucosal surface contact: it is recommend to
wash the contacted site profusely with water or
sterile saline solution.
The CDC (2001) does not recommend IG or antivi-
ral agents for post-exposure prophylaxis of hepati-
tis C. Individuals exposed to the virus through an
occupational accident should follow the recommen-
dations above and undergo diagnostic tests to fol-
low up the accident (Fig 2). The most effective
measure to prevent occupational transmission of
HCV is to adopt universal precautions, including
hand washing, the appropriate use of barrier pre-
cautions (for example, gloves, masks and protec-
tive eyewear) and the safe handling of sharp instru-
ments to prevent occupational exposures to blood.
In addition, health professionals should be encour-
aged to report accidents, adopt universal precau-
tions and be familiar with the main aspects of HCV,
since some studies have shown that most health-
care workers did not adopt these measures (Silva
et al, 2009; Silva et al, 2012; Myers, 2012).
CONCLUSION
Dental health workers should recognise the main
aspects regarding HCV transmission, diagnosis
and prevention in order to manage HCV-positive in-
dividuals during dental treatment. During dental
treatment of HCV-positive patients, dental health
workers must perform a thorough and accurate
evaluation of the patient and should promote edu-
cational, prophylactic and oral health interventions.
Thus, the following procedures should be adopted
by dental health workers: (i) provide oral health
educational activities; (ii) order laboratory exams in
suspected cases; (iii) refer suspected or confirmed

6 Oral Health & Preventive Dentistry


HCV patients for medical treatment; (iv) work to-
gether with the medical team for dental treatment
management; (v) identify oral manifestations relat-
ed to hepatitis C; (vi) adopt universal precautions
to prevent occupational transmission of HCV.
ACKNOWLEDGEMENTS
The authors would like to thank the Coordination of the Improve-
ment of Higher Education Personnel (CAPES), Fundação de Amparo
a Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for fi-
nancial support.
REFERENCES
1. Alter MJ. Epidemiology of hepatitis C virus infection. World
J Gastroenterol 2007;13:2436–2441.
2. Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares
A, Alexander WJ, et al. The natural history of community-
acquired hepatitis C in the United States. The Sentinel
Counties Chronic non-A, non-B Hepatitis Study Team. N
Engl J Med 1992;327:1899–1905.
3. Alter HJ, Purcell RH, Shih JW, Melpolder JC,  Houghton
M, Choo QL et al Detection of antibody to hepatitis C virus
in prospectively followed transfusion recipients with acute
and chronic non-A, non-B hepatitis. N Engl J Med
1989;321:1494–1500.
4. Amado LA, Villar LM, de Paula VS, de Almeida AJ, Gaspar
AM. Detection of hepatitis A, B, and C virus-specific anti-
bodies using oral fluid for epidemiological studies. Mem
Inst Oswaldo Cruz 2006;101:149–155.
5. Ammon A, Reichart PA, Pauli G, Petersen LR. Hepatitis B
and C among Berlin dental personnel: incidence, risk fac-
tors, and effectiveness of barrier prevention measures.
Epidemiol Infect 2000 125:407–413.
6. Ashfaq UA, Javed T, Rehman S, Nawaz Z, Riazuddin S. An
overview of HCV molecular biology, replication and im-
mune responses. Virol J 2011;11:161.
7. Ashkenazi M, Fisher N, Levin L, Littner MM. Seroepidemi-
ology of hepatitis C antibodies among dentists and their
self-reported use of infection control measures. Commu-
nity Dent Health 2009;26: 99–103.
8. Barghout N, Habashneh RA, Ryalat ST, Asa‘ad FA, Marash-
deh, M. Patients’ perception of cross-infection prevention
in dentistry in Jordan. Oral Health Prev Dent 2012;1: 9–16.
9. Bouvier-Alias M, Patel K, Dahari H, Beaucourt S, Larderie
P,  Blatt L, et al. Clinical utility of total HCV core antigen
quantification: a new indirect marker of HCV replication.
Hepatology 2002;36:211–218.
10. Brasil. Ministério da Saúde. Exposição a materiais biológi-
cos. Brasília: Ministério da Saúde;2006.
11. Brasil. Ministério da Saúde. Hepatites virais. Available at
http://www.aids.gov.br/sites/default/files/anexos/publi-
c a c a o/2 011 /5 0 073/b o l e t i m _ h e p a t i t e s 2 011 _
pdf_64874.pdf, Accessed 1 July 2012.
12. Bukh J. Animal models for the study of hepatitis C virus
infection and related liver disease. Gastroenterolo-
gy 2012;142: 1279–1287.
doi: 10.3290/j.ohpd.a32134
Garbin et al
13. Caldeira PC, Oliveira E Silva KR, Silva TA, de Mattos Cama-
rgo Grossmann S, Teixeira R, Carmo MA. Correlation be-
tween salivary anti-HCV antibodies and HCV RNA in saliva
and salivary glands of patients with chronic hepatitis C. J
Oral Pathol Med 2012 Aug 27; [Epub ahead of print] doi:
10.1111/j.1600–0714.2012.01201.x.
14. Carr AJ, Ng WF, Figueiredo F, Macleod RI, Greenwood M,
Staines K. Sjögren’s syndrome: an update for dental prac-
titioners. Br Dent J 2012;213:353–357.
15. Carrozzo M. Oral diseases associated with hepatitis C vi-
rus infection. Part 1. sialadenitis and salivary glands lym-
phoma. Oral Dis 2008;14:123–130.
16. CDC. Centers for Disease Control and Prevention. Recom-
mendations for prevention and control of hepatitis C virus
(HCV) infection and HCV-related chronic disease. MMWR
Recomm Rep 1998;47:1–39.
17. CDC. Centers for Disease Control and Prevention. Updat-
ed U.S. Public Health Service Guidelines for the Manage-
ment of Occupational Exposures to HBV, HCV, and HIV and
Recommendations for Postexposure Prophylaxis. MMWR
2001;50(No. RR-11):[inclusive page numbers].
18. Chevaliez S. Virological tools to diagnose and monitor
hepatitis C virus infection. Clin Microbiol Infect
2011;17:116–121.
19. Choo QL, Weiner AJ, Overby LR, Kuo G, Houghton M, Brad-
ley DW. Hepatitis C virus: the major causative agent of vi-
ral non-A, non-B hepatitis. Br Med Bull 1990;46:423–441.
20. Cruz HM, Marques VA, Villela-Nogueira CA, do Ó KM, Lew-
is-Ximenez LL, Lampe E, Villar LM. An evaluation of differ-
ent saliva collection methods for detection of antibodies
against hepatitis C virus (anti-HCV). J Oral Pathol Med
2012;41:793–800.
21. Diago M, Shiffman ML, Bronowicki JP, Zeuzem S, Rodri-
guez-Torres M, Pappas SC, et al. Identifying hepatitis C
virus genotype 2/3 patients who can receive a 16-week
abbreviated course of peginterferon alfa-2a (40KD) plus
ribavirin. Hepatology 2010;51:1897–1903.
22. Dougall A, Fiske J. Access to special care dentistry, part 5.
Safety. Br Dent J 2008;205:177–190.
23. El-Serag HB, Mason AC, Key C: Trends in survival of pa-
tients with hepatocellular carcinoma between 1977 and
1996 in the United States. Hepatology 2001;33: 62–65.
24. Esteban JI, Gomez J, Martell M, Cabot B, QuerJ, Camps J,
et al. Transmission of hepatitis C virus by a cardiac sur-
geon. N Engl J Med 1996;334:555–560.
25. Fattovich G, Giustina G, Degos F, Tremolada F,  Diodati
G, Almasio P, et al. Morbidity and mortality in compensat-
ed cirrhosis type C: a retrospective follow-up study of 384
patients. Gastroenterology 1997;112:463–472.
26. Feinstone SM, Hu DJ, Major ME. Prospects for prophylac-
tic and therapeutic vaccines against hepatitis C virus. Clin
Infect Dis 2012;55(suppl 1):S25-32.
27. Figueiredo LC, Carrilho FJ, Andrage HF, Migliari DA. Oral li-
chen planus and hepatitis C virus infection. Oral Dis
2002;8:42–46.
28. Galossi A, Guarisco R, Bellis L, Puoti C. Extrahepatic man-
ifestations of chronic HCV infection. J Gastrointestin Liver
Dis 2007;16:65–73.
29. Golla K, Epstein JB, Cabay RJ. Liver disease: current per-
spectives on medical and dental management. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 2004;98:516–521.
30. Grossmann Sde M, Teixeira R, de Aguiar MC, de Moura
MD, do Carmo MA. Oral mucosal conditions in chronic
hepatitis C Brazilian patients: a cross-sectional study. J
Public Health Dent 2009;69:168–175.
7
Garbin et al
31. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V,  Diago
M,  Marcellin P,  et al. Peginterferonalpha2a and ribavirin
combination therapy in chronic hepatitis C: a randomized
study of treatment duration and ribavirin dose. Ann Intern
Med 2004;140:346–355.
32. 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.
33. Jafari S, Copes R, Baharlou S, Etminan M, Buxton J. Tat-
tooing and the risk of transmission of hepatitis C: a sys-
tematic review and meta-analysis. Int J Infect Dis
2010;14:e928–e940.
34. Jauncey M, Micallef JM, Gilmour S, Amin J, White PA, Raw-
linson W,  et al. Clearance of hepatitis C virus after newly
acquired infection in injection drug users. J Infect Dis
2004;190:1270–1274.
35. Kamili S, Krawczynski K, McCaustland KA, Li X, Alter MJ.
Infectivity of hepatitis C virus after drying and storing at
room temperature. Infect Control Hosp Epidemiol
2007;28:519–524.
36. Kershenobich D, Razavi HA, Sánchez-Avila JF, Bessone
F, Coelho HS, Dagher L,  et al. Trends and projections of
hepatitis C virus epidemiology in Latin America. Liver Int
2011 31(Supp2):18–29.
37. Khattab MA, Eslam M, Alavian SM. Hepatitis C virus as a
multifaceted disease: a simple and updated approach for
extrahepatic manifestations of hepatitis C virus infection.
Hepat Mon 2010;10:258–269.
38. Klein RS, Freeman K, Taylor PE, Stevens CE. Occupational
risk for hepatitis C virus infection among New York City
dentists. Lancet 1991;338:1539–1542.
39. Konidena A, Pavani BV. Hepatitis C virus infection in pa-
tients with oral lichen planus. Niger J Clin Pract
2011;14:228–231.
40. Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell
RH, Miyamura T,  et al. An assay for circulating antibodies
to a major etiologic virus of human non-A, non-B hepatitis.
Science 1989;244(4902):362–364.
41. Laperche S, Le Marrec N,Girault A, Bouchardeau1 F,  Serv-
ant-Delmas A, Maniez-Montreuil M,  et al. Simultaneous
detection of hepatitis C virus (HCV) core antigen and anti
HCV antibodies improves the early detection of HCV infec-
tion. J Clin Microbiol 2005;43:3877–3883.
42. Lavanchy D. Evolving epidemiology of hepatitis C virus.
Clin Microbiol Infect 2011;17:107–115.
43. Lock G, Dirscherl M, Obermeier F, Gelbmann CM,  Heller-
brand C, Knöll A, et al. Hepatitis C - contamination of tooth-
brushes: myth or reality? J Viral Hepat 2006;13:571–573.
44. Lodi G, Porter SR, Scully C. Hepatitis C virus infection:
Review and implications for the dentist. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 1998;86:8–22.
45. Martins T, Narciso-Schiavon JL, Schiavon Lde L. Epidemi-
ology of hepatitis C virus infection [in Portugese]. Rev As-
soc Med Bras 2011;57:107–112.
46. Myers JE, Myers R, Wheat Me, Yin MT. Dental students
and bloodborne pathogens: occupational exposures,
knowledge, and attitudes. J Dent Educ 2012;76:479–486
47. Nagao Y, Sata M. Dental problems delaying the initiation
of interferon therapy for HCV-infected patients. Virol J
2010;7:192.
48. Nayak NC, Jain D, Vasdev N, Gulwani H, Saigal S, Soin A.
Etiologic types of end-stage chronic liver disease in adults:
analysis of prevalence and their temporal changes from a
8 Oral Health & Preventive Dentistry
study on native liver explants. Eur J Gastroenterol Hepatol
2012;24:1199–1208.
49. NIH. National Institutes of Health.Consensus Statement
on Management of Hepatitis C: 2002. NIH Consens State
Sci Statements 2002;19:1–46.
50. Park Y, Lee JH, Kim BS, Kim do Y, Han KH, HS Kim. New
automated hepatitis C virus (HCV) core antigen assay as
an alternative to real-time PCR for HCV RNA quantification.
J Clin Microbiol 2010;48:2253–2256.
51. Pawlotsky JM. Use and interpretation of virological tests
for hepatitis C. Hepatology 2002;36(5 suppl 1):S65–73.
52. Pearlman BL, Traub N. Sustained virologic response to an-
tiviral therapy for chronic hepatitis C virus infection: a cure
and so much more. Clin Infect Dis 2011;52:889–900.
53. Perz JF, Farrington LA, Pecoraro C, Hutin YJF, Armstrong
GL. Estimated global prevalence of hepatitis C virus infec-
tion [abstract]. In: 42nd Annual Meeting of the Infectious
Diseases Society of America, Boston, MA, USA;Sept 30–
Oct 3, 2004. Available at https://idsa.confex.com/
idsa/2004/webprogram/Paper20026.html
54. Resende VLS, Abreu MHG, Paiva SM, Teixeira R, Pordeus
IA. Factors associated with seroprevalence of hepatitis C
among dentists at a large Brazilian city. Virol J 2009;6:228.
55. SBH. Relatório do Grupo de Estudo da Sociedade Brasilei-
ra de Hepatologia. Epidemiologia da infecção pelo vírus
da hepatite C no Brasil. GED 1999;18:53–58.
56. Scott JD, McMahon BJ, Bruden D, Sullivan D, Homan C,
Christensen C, et al. High rate of spontaneous negativity for
hepatitis C virus RNA after establishment of chronic infec-
tion in Alaska Natives. Clin Infect Dis 2006;42:945–952.
57. Scully C, Felix DH. Oral medicine: update for the dental
practitioner: dry mouth and disorders of salivation. Br
Dent J 2005;199:423–427.
58. Seeff LB, Buskell-Bales Z, Wright EC, Durako JS, Alter HJ,
Iber FL, et al. Long-term mortality after transfusion-asso-
ciated non-A, non-B hepatitis. The National Heart, Lung,
and Blood Institute Study Group. N Engl J Med
1992;327:1906–1911.
59. Serfaty L, Aumaitre H, Chazouilleres O, Bonnand AM, Ros-
morduc O, Poupon RE, et al. Determinants of outcome of
compensated hepatitis C virus-related cirrhosis. Hepatol-
ogy 1998;27:1435–1440.
60. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hep-
atitis C virus infection. Lancet Infect Dis 2005;5:558–567.
61. Silva GS, Almeida, AJ, Paula VS, Villar LM. Conhecimento
e utilização de medidas de precaução-padrão por profis-
sionais de saúde [Epub]. Esc Anna Nery 2012;16:103–
110. Available at http://dx.doi.org/10.1590/S1414-
81452012000100014
62. Silva JA, Paula VS, Almeida AJ, Villar LM. Investigação de
acidentes biológicos entre profissionais de saúde. Esc
Anna Nery [online]. 2009;13:508–516. Available at http://
dx.doi.org/10.1590/S1414-81452009000300008 
63. Simmonds P, Bukh J, Combet C, Deléage G,  Enomoto
N, Feinstone S, et al. Consensus proposals for a unified
system of nomenclature of hepatitis C virus genotypes.
Hepatology 2005;42:962–973.
64. Sy T, Jamal MM. Epidemiology of hepatitis C virus (HCV)
infection. Int J Med Sci 2006;3:41–46.
65. Takahama AJ, Tatsch F, Tannus G, Lopes MA. Hepatitis C:
incidence and knowledge among Brazilian dentists. Com-
munity Dent Health 2005;22:184–187.

66. The Global Burden of Hepatitis C Working Group.  Global
burden of disease (GBD) for hepatitis C. J Clin Pharmacol
2004;44:20–29.
67. Thomas DL, Gruninger SE, Siew C, Joy ED, Quinn TC. Oc-
cupational risk of hepatitis C infections among general
dentists and oral surgeons in North America. Am J Med
1996;100:41–45.
68. Tsude K, Fujiyama S, Sato S, Kawano S, Taura Y, Yoshida K,  73. Wilkins T, Malcolm JK, Raina D;Schade RR. Hepatitis C:
et al. Two cases of accidental transmission of hepatitis C to
medical staff. Hepatogastroenterology 1992;39:73–75.
69. Vaglia A, Nicolin R, Puro V, Ippolito G, Bttini C, de Lalla F.
Needlestick hepatitis C virus seroconversion in a surgeon.
Lancet 1990;336:1315–1316.
70. Waheed Y, Safi SZ, Qadri I. Role of Potash Alum in hepati-
tis C virus transmission at barber‘s shop. Virol J 2011;8:
211.
doi: 10.3290/j.ohpd.a32134
Garbin et al
71. Weber C, Collet-Schaub D, Fried R, Lambrecht JT, Erb P,
Meyer J. Low prevalence of hepatitis C virus antibody
among Swiss dental healthcare workers. J Hepatol
2001;34:963–964.
72. WHO. World Health Organization. HepatitisC. Available at
http://www.who.int/mediacentre/ factsheets/fs164/en/,
Accessed 30 July 2012.
diagnosis and treatment.  Am Fam Physician 2010;81:
1351–1357.
74. Yen T, Keeffe EB, Ahmed A. The epidemiology of hepatitis
C virus infection. J Clin Gastroenterol 2003;36:47–53.
9