REVIEW 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 important 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 purpose 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 Oral Health Prev Dent 2014;12:313-321 doi: 10.3290/j.ohpd.a32134
I
n the 1970s, researchers observed that most cases of post-transfusion hepatitis were not attributable to either hepatitis A or hepatitis B viral infection, 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 retrospective 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 Dentistry Postgraduate Programme, Universidade Estadual Paulista (UNESP), Araçatuba, SP, Brazil.
b
Master’s Degree Candidate, Preventive and Social Dentistry Postgraduate 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 Postgraduate Programme, Universidade Estadual Paulista (UNESP), Araçatuba, 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, Programa de Pós-graduação em Odontologia Preventiva e Social; NEPESCO, 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: [email protected]
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Submitted for publication: 12.12.12; accepted for publication: 14.03.13
EPIDEMIOLOGY HCV infection presents a global prevalence around 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 million 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, different prevalence rates of HCV infection are observed around the world (Shepard et al, 2005; Kershenobich 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 America (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 donors from 5 geographical regions showed higher prevalence in the northern region (2.12%), low prevalence in the southern region (0.65%) and an
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Exposure to HCV 1–2 weeks Infection with HCV
No infection with HCV
0 to 20 years of disease evolution
Acute hepatitis C (25% symptomatic, 75% asymptomatic)
Chronic hepatitis C (60–85%)
Spontaneous elimination of HCV (0.50–0.74%)
Infection clears (15–40%)
Absence of fibrosis and inflammation
Presence of fibrosis and inflammation
Cirrhosis (20%)
Uncompensated cirrhosis (4%)
Death (industrialised countries,15%; developing countries, 30%)
Hepatocellular carcinoma (1.6%)
Liver transplant
Death (industrialised countries, 80%; 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 worldwide, varying from 0.4% to 0.9% in Brazil (Takahama 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 genome and is classified in the Flaviviridae family, Hepacivirus genus. Hepatitis C virus is classified into six genotypes (1–6), each of which has related
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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 infection is presented in Fig 1.
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Only 20%–30% of cases present symptoms, such as: abdominal, muscular, or joint pain; fatigue; anorexia; fever; nausea; jaundice; dark urine and pale feces. A physical exam can show an increase 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 infection have been observed, for instance, significant association between HCV and the following diseases are supported by sufficient data: mixed cryoglobulinemia, B-cell-derived non-Hodgkin’s lymphoma (NHL), diabetes mellitus, porphyria cutanea tarda and lichen planus. Other manifestations still require confirmation and a more detailed characterisation with respect to similar pathologies of different aetiology or idiopathic nature: idiopathic pulmonary fibrosis, autoimmune thyroiditis, sicca syndrome, noncryoglobulinaemic nephropathies and glomerulonephritis as well as aortic atherosclerosis (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 contaminated blood (i.e. accidents with needles or sharp objects) or by exposure of mucosa to blood or haemoderivative products, such as during childbirth or unprotected sex with HCV-infected partners (CDC, 1998). Thus, individuals at high risk for HCV infection are those who received blood transfusions or haemoderivatives before 1992, when antiHCV tests were not mandatory at blood banks, patients on haemodialysis, haemophiliacs, prisoners, the sexually promiscuous, transplant recipients, people with tattoos and piercings and illicit intravenous drug users (CDC, 1998; Jafari et al, 2010). There are several reports of health-care workers who contracted HCV infection after needle-stick injury (Vaglia et al, 1990; Seeff et al, 1992; Tsude et al, 1992). Transmission of HCV from health-care
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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 transmission have been discussed, such as barber and acupuncture services, scarification rituals and circumcision (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 crossinfection control and education reinforcement is imperative (Barghout et al, 2012).
DIAGNOSIS HCV diagnosis is based on the detection of antiHCV antibodies by third generation ELISA assays. These assays can detect anti-HCV antibodies on average 2–8 weeks after the acute phase of infection and persist for life in patients who develop chronic HCV infection (Chevaliez, 2011). Assays to detect HCV core antigen demonstrated a significant relationship to the HCV RNA level measured by means of a molecular biology technique, 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 developed as HCV combination assays that detect acute HCV infection on average 20 days before third-generation antibody-only assays, but they are less sensitive than third-generation anti-HCV assays for antibody detection and detect HCV infection later than HCV RNA assays (Laperche et al, 2005). In order to identify active infection (HCV RNA detected) or recovery (HCV RNA not detected), antiHCV 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 antibodies, 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 antiviral therapy and document treatment failure (Pawlotsky, 2002).
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TREATMENT AND PREVENTION The current standard treatment for chronic hepatitis C infection is the combination of pegylated IFNa2a or IFN-a2b and ribavirin (NIH, 2002). The future standard treatment of chronic genotype-1 hepatitis C will be the triple combination of pegylated IFNa2a or IFN-a2b, ribavirin and a protease inhibitor, boceprevir or telaprevir. The efficacy endpoint of chronic hepatitis C treatment is the sustained virological response (SVR), defined as an undetectable HCV RNA load in serum with a sensitive assay (lower limit of detection of 10–15 IU/ml) 24 weeks after the end of treatment (Chevaliez, 2011). The duration of treatment, dose of ribavirin, virological monitoring procedure and rate of SVR depends 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. Individuals 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% (Diago 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 administered should be evaluated (Hadziyannis et al, 2004). The aims of HCV treatment are to alleviate liver fibrosis, reduce transaminase levels, prevent hepatocellular carcinoma, improve the patient’s quality of life and knock down the HCV viral load, helping to prevent the dissemination of the disease by reducing the number of people who can transmit it (Pearlman and Traub, 2011). Before HCV treatment, it is recommended that the oral health of the patients be evaluated. If oral diseases such as periodontitis and pulpitis are present, the beginning 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 reduced resistance to infection (Nagao and Sata, 2010). In order to prevent HCV infection, the development of health education programmes is recommended, as is identifying HCV infected individuals in high risk groups. Dental health-care workers can contribute to preventing HCV infection by using adequate 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
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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 instruments, 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 hepatitis C due to various obstacles, such as: high genetic and antigenic diversity, with at least six different 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 virus-like particles (Feinstone et al, 2012).
ORAL HEALTH AND MANAGEMENT AMONG HCV-POSITIVE INDIVIDUALS Up to 74% of patients infected with HCV can develop at least one extra-hepatic manifestation during the course of the disease (Galossi et al, 2007) and some of these manifestations can cause oral problems and/or indicate the need for special care when performing dental interventions. The oral cavity can exhibit signs of liver problems in the form of various disorders and diseases (Table 1).
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Among extrahepatic manifestations of HCV infection involving the oral region, lichen planus and Sjögren’s syndrome (SS) are the most discussed. HCV-infected patients may frequently present histological 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 related sicca syndrome in HCV is unclear. It is unclear whether the virus may cause a disease mimicking 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 lymphomagenesis, particularly among individuals presenting mixed cryoglobulinemia (Carrozzo, 2008). A recent study among HCV patients in Brazil showed that 96.3% of them presented oral mucosal 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 patient 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 importance of asking patients about their use of medications must be emphasised. In addition to obtaining a well-performed medical history, the dentist needs to work with an interdisciplinary team to understand the liver damage of the patients and their general state of health. The objectives of dental care in HCV patients are to evaluate their susceptibility 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 treatment 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 carious lesions, basic periodontal treatments, adjustment of prostheses, tooth extraction and endodontic treatments (Dougall and Fiske J, 2008; Nagao and Sata, 2010). Preventive and educational dental procedures, such as orientation about oral hygiene and diet, supragingival prophylaxis and the topical use of fluoride should be performed independent of the stage of liver disease. HCV-infected
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individuals present a high risk of caries and periodontal disease due to decreased salivary flow (hyposalivation) in the former (Scully and Felix, 2005) and poor bucal hygiene, insulin resistance or prolonged bleeding in the latter (Nagao and Sata, 2010). Before performing invasive procedures such as tooth extraction, periodontal surgery and the administration of local anaesthetic, dental surgeons should order blood tests, such as platelet count prothrombin time/INR (international normalised ratios) 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 physician 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 invasive dental procedures, dental surgeons can use local anaesthetics with a vasoconstrictor or haemostatic agent in cavities (oxidised cellulose or collagen 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 surgeon should also advise patients on post-operative care and measures to prevent post-operative complications; in addition, the dental surgeon should not not prescribe or administer potentially hepatotoxic 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 instruments. Every year, approximately 3 million health professionals (about 10% of this job category) report some percutaneous exposure worldwide, and it is estimated that these accidents result in 15,000 hepatitis C infections per year (WHO, 2012). Since HCV is most efficiently transmitted through percutaneous exposures to blood, there is a potential risk for dental health workers during their occupational activities; it was observed that dental students are frequently exposed to needle-stick accidents (Silva et al, 2009). However, follow-up studies of health care workers exposed to HCV-infected blood through percutaneous or other sharp-instru-
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Exposure to HCV
Alanine aminotransferase
Normal
Elevated
Repeat at 1, 3, and 6 months
Normal
Anti-HCV
Positive
Negative
Hepatopathy
Repeat at 1, 3, and 6 months
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; Resende 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 affected area should be washed very carefully with water and soap. No evidence exists that using antiseptics 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 antiviral agents for post-exposure prophylaxis of hepatitis C. Individuals exposed to the virus through an occupational accident should follow the recommendations above and undergo diagnostic tests to follow up the accident (Fig 2). The most effective
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measure to prevent occupational transmission of HCV is to adopt universal precautions, including hand washing, the appropriate use of barrier precautions (for example, gloves, masks and protective eyewear) and the safe handling of sharp instruments to prevent occupational exposures to blood. In addition, health professionals should be encouraged to report accidents, adopt universal precautions and be familiar with the main aspects of HCV, since some studies have shown that most healthcare 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 individuals 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 educational, 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
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HCV patients for medical treatment; (iv) work together with the medical team for dental treatment management; (v) identify oral manifestations related to hepatitis C; (vi) adopt universal precautions to prevent occupational transmission of HCV.
ACKNOWLEDGEMENTS The authors would like to thank the Coordination of the Improvement 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 financial support.
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study on native liver explants. Eur J Gastroenterol Hepatol 2012;24:1199–1208. NIH. National Institutes of Health.Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements 2002;19:1–46. 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. Pawlotsky JM. Use and interpretation of virological tests for hepatitis C. Hepatology 2002;36(5 suppl 1):S65–73. Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis 2011;52:889–900. Perz JF, Farrington LA, Pecoraro C, Hutin YJF, Armstrong GL. Estimated global prevalence of hepatitis C virus infection [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 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. SBH. Relatório do Grupo de Estudo da Sociedade Brasileira de Hepatologia. Epidemiologia da infecção pelo vírus da hepatite C no Brasil. GED 1999;18:53–58. 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 infection in Alaska Natives. Clin Infect Dis 2006;42:945–952. Scully C, Felix DH. Oral medicine: update for the dental practitioner: dry mouth and disorders of salivation. Br Dent J 2005;199:423–427. Seeff LB, Buskell-Bales Z, Wright EC, Durako JS, Alter HJ, Iber FL, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med 1992;327:1906–1911. Serfaty L, Aumaitre H, Chazouilleres O, Bonnand AM, Rosmorduc O, Poupon RE, et al. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology 1998;27:1435–1440. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005;5:558–567. Silva GS, Almeida, AJ, Paula VS, Villar LM. Conhecimento e utilização de medidas de precaução-padrão por profissionais de saúde [Epub]. Esc Anna Nery 2012;16:103– 110. Available at http://dx.doi.org/10.1590/S141481452012000100014 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 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. Sy T, Jamal MM. Epidemiology of hepatitis C virus (HCV) infection. Int J Med Sci 2006;3:41–46. Takahama AJ, Tatsch F, Tannus G, Lopes MA. Hepatitis C: incidence and knowledge among Brazilian dentists. Community Dent Health 2005;22:184–187.
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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. 73. Wilkins T, Malcolm JK, Raina D;Schade RR. Hepatitis C: 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.
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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 important 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 purpose 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 Oral Health Prev Dent 2014;12:313-321 doi: 10.3290/j.ohpd.a32134
I
n the 1970s, researchers observed that most cases of post-transfusion hepatitis were not attributable to either hepatitis A or hepatitis B viral infection, 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 retrospective 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 Dentistry Postgraduate Programme, Universidade Estadual Paulista (UNESP), Araçatuba, SP, Brazil.
b
Master’s Degree Candidate, Preventive and Social Dentistry Postgraduate 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 Postgraduate Programme, Universidade Estadual Paulista (UNESP), Araçatuba, 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, Programa de Pós-graduação em Odontologia Preventiva e Social; NEPESCO, 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: [email protected]
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Submitted for publication: 12.12.12; accepted for publication: 14.03.13
EPIDEMIOLOGY HCV infection presents a global prevalence around 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 million 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, different prevalence rates of HCV infection are observed around the world (Shepard et al, 2005; Kershenobich 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 America (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 donors from 5 geographical regions showed higher prevalence in the northern region (2.12%), low prevalence in the southern region (0.65%) and an
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Exposure to HCV 1–2 weeks Infection with HCV
No infection with HCV
0 to 20 years of disease evolution
Acute hepatitis C (25% symptomatic, 75% asymptomatic)
Chronic hepatitis C (60–85%)
Spontaneous elimination of HCV (0.50–0.74%)
Infection clears (15–40%)
Absence of fibrosis and inflammation
Presence of fibrosis and inflammation
Cirrhosis (20%)
Uncompensated cirrhosis (4%)
Death (industrialised countries,15%; developing countries, 30%)
Hepatocellular carcinoma (1.6%)
Liver transplant
Death (industrialised countries, 80%; 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 worldwide, varying from 0.4% to 0.9% in Brazil (Takahama 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 genome and is classified in the Flaviviridae family, Hepacivirus genus. Hepatitis C virus is classified into six genotypes (1–6), each of which has related
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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 infection is presented in Fig 1.
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Only 20%–30% of cases present symptoms, such as: abdominal, muscular, or joint pain; fatigue; anorexia; fever; nausea; jaundice; dark urine and pale feces. A physical exam can show an increase 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 infection have been observed, for instance, significant association between HCV and the following diseases are supported by sufficient data: mixed cryoglobulinemia, B-cell-derived non-Hodgkin’s lymphoma (NHL), diabetes mellitus, porphyria cutanea tarda and lichen planus. Other manifestations still require confirmation and a more detailed characterisation with respect to similar pathologies of different aetiology or idiopathic nature: idiopathic pulmonary fibrosis, autoimmune thyroiditis, sicca syndrome, noncryoglobulinaemic nephropathies and glomerulonephritis as well as aortic atherosclerosis (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 contaminated blood (i.e. accidents with needles or sharp objects) or by exposure of mucosa to blood or haemoderivative products, such as during childbirth or unprotected sex with HCV-infected partners (CDC, 1998). Thus, individuals at high risk for HCV infection are those who received blood transfusions or haemoderivatives before 1992, when antiHCV tests were not mandatory at blood banks, patients on haemodialysis, haemophiliacs, prisoners, the sexually promiscuous, transplant recipients, people with tattoos and piercings and illicit intravenous drug users (CDC, 1998; Jafari et al, 2010). There are several reports of health-care workers who contracted HCV infection after needle-stick injury (Vaglia et al, 1990; Seeff et al, 1992; Tsude et al, 1992). Transmission of HCV from health-care
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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 transmission have been discussed, such as barber and acupuncture services, scarification rituals and circumcision (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 crossinfection control and education reinforcement is imperative (Barghout et al, 2012).
DIAGNOSIS HCV diagnosis is based on the detection of antiHCV antibodies by third generation ELISA assays. These assays can detect anti-HCV antibodies on average 2–8 weeks after the acute phase of infection and persist for life in patients who develop chronic HCV infection (Chevaliez, 2011). Assays to detect HCV core antigen demonstrated a significant relationship to the HCV RNA level measured by means of a molecular biology technique, 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 developed as HCV combination assays that detect acute HCV infection on average 20 days before third-generation antibody-only assays, but they are less sensitive than third-generation anti-HCV assays for antibody detection and detect HCV infection later than HCV RNA assays (Laperche et al, 2005). In order to identify active infection (HCV RNA detected) or recovery (HCV RNA not detected), antiHCV 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 antibodies, 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 antiviral therapy and document treatment failure (Pawlotsky, 2002).
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TREATMENT AND PREVENTION The current standard treatment for chronic hepatitis C infection is the combination of pegylated IFNa2a or IFN-a2b and ribavirin (NIH, 2002). The future standard treatment of chronic genotype-1 hepatitis C will be the triple combination of pegylated IFNa2a or IFN-a2b, ribavirin and a protease inhibitor, boceprevir or telaprevir. The efficacy endpoint of chronic hepatitis C treatment is the sustained virological response (SVR), defined as an undetectable HCV RNA load in serum with a sensitive assay (lower limit of detection of 10–15 IU/ml) 24 weeks after the end of treatment (Chevaliez, 2011). The duration of treatment, dose of ribavirin, virological monitoring procedure and rate of SVR depends 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. Individuals 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% (Diago 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 administered should be evaluated (Hadziyannis et al, 2004). The aims of HCV treatment are to alleviate liver fibrosis, reduce transaminase levels, prevent hepatocellular carcinoma, improve the patient’s quality of life and knock down the HCV viral load, helping to prevent the dissemination of the disease by reducing the number of people who can transmit it (Pearlman and Traub, 2011). Before HCV treatment, it is recommended that the oral health of the patients be evaluated. If oral diseases such as periodontitis and pulpitis are present, the beginning 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 reduced resistance to infection (Nagao and Sata, 2010). In order to prevent HCV infection, the development of health education programmes is recommended, as is identifying HCV infected individuals in high risk groups. Dental health-care workers can contribute to preventing HCV infection by using adequate 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
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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 instruments, 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 hepatitis C due to various obstacles, such as: high genetic and antigenic diversity, with at least six different 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 virus-like particles (Feinstone et al, 2012).
ORAL HEALTH AND MANAGEMENT AMONG HCV-POSITIVE INDIVIDUALS Up to 74% of patients infected with HCV can develop at least one extra-hepatic manifestation during the course of the disease (Galossi et al, 2007) and some of these manifestations can cause oral problems and/or indicate the need for special care when performing dental interventions. The oral cavity can exhibit signs of liver problems in the form of various disorders and diseases (Table 1).
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Among extrahepatic manifestations of HCV infection involving the oral region, lichen planus and Sjögren’s syndrome (SS) are the most discussed. HCV-infected patients may frequently present histological 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 related sicca syndrome in HCV is unclear. It is unclear whether the virus may cause a disease mimicking 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 lymphomagenesis, particularly among individuals presenting mixed cryoglobulinemia (Carrozzo, 2008). A recent study among HCV patients in Brazil showed that 96.3% of them presented oral mucosal 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 patient 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 importance of asking patients about their use of medications must be emphasised. In addition to obtaining a well-performed medical history, the dentist needs to work with an interdisciplinary team to understand the liver damage of the patients and their general state of health. The objectives of dental care in HCV patients are to evaluate their susceptibility 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 treatment 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 carious lesions, basic periodontal treatments, adjustment of prostheses, tooth extraction and endodontic treatments (Dougall and Fiske J, 2008; Nagao and Sata, 2010). Preventive and educational dental procedures, such as orientation about oral hygiene and diet, supragingival prophylaxis and the topical use of fluoride should be performed independent of the stage of liver disease. HCV-infected
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individuals present a high risk of caries and periodontal disease due to decreased salivary flow (hyposalivation) in the former (Scully and Felix, 2005) and poor bucal hygiene, insulin resistance or prolonged bleeding in the latter (Nagao and Sata, 2010). Before performing invasive procedures such as tooth extraction, periodontal surgery and the administration of local anaesthetic, dental surgeons should order blood tests, such as platelet count prothrombin time/INR (international normalised ratios) 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 physician 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 invasive dental procedures, dental surgeons can use local anaesthetics with a vasoconstrictor or haemostatic agent in cavities (oxidised cellulose or collagen 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 surgeon should also advise patients on post-operative care and measures to prevent post-operative complications; in addition, the dental surgeon should not not prescribe or administer potentially hepatotoxic 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 instruments. Every year, approximately 3 million health professionals (about 10% of this job category) report some percutaneous exposure worldwide, and it is estimated that these accidents result in 15,000 hepatitis C infections per year (WHO, 2012). Since HCV is most efficiently transmitted through percutaneous exposures to blood, there is a potential risk for dental health workers during their occupational activities; it was observed that dental students are frequently exposed to needle-stick accidents (Silva et al, 2009). However, follow-up studies of health care workers exposed to HCV-infected blood through percutaneous or other sharp-instru-
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Exposure to HCV
Alanine aminotransferase
Normal
Elevated
Repeat at 1, 3, and 6 months
Normal
Anti-HCV
Positive
Negative
Hepatopathy
Repeat at 1, 3, and 6 months
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; Resende 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 affected area should be washed very carefully with water and soap. No evidence exists that using antiseptics 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 antiviral agents for post-exposure prophylaxis of hepatitis C. Individuals exposed to the virus through an occupational accident should follow the recommendations above and undergo diagnostic tests to follow up the accident (Fig 2). The most effective
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measure to prevent occupational transmission of HCV is to adopt universal precautions, including hand washing, the appropriate use of barrier precautions (for example, gloves, masks and protective eyewear) and the safe handling of sharp instruments to prevent occupational exposures to blood. In addition, health professionals should be encouraged to report accidents, adopt universal precautions and be familiar with the main aspects of HCV, since some studies have shown that most healthcare 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 individuals 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 educational, 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
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HCV patients for medical treatment; (iv) work together with the medical team for dental treatment management; (v) identify oral manifestations related to hepatitis C; (vi) adopt universal precautions to prevent occupational transmission of HCV.
ACKNOWLEDGEMENTS The authors would like to thank the Coordination of the Improvement 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 financial support.
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