Correlation between salivary anti-HCV antibodies and HCV RNA in saliva and salivary glands of patients with chronic hepatitis C.

BACKGROUND: To investigate the correlation between anti-hepatitis C virus (HCV) antibodies in saliva and detection of HCV RNA in saliva and salivary glands of patients with chronic hepatitis C. METHODS: A total of 180 samples of saliva (131 non-stimulated and 49 stimulated) from 133 patients with chronic hepatitis C were tested by ELISA for presence of anti-HCV antibodies. Results were compared with the detection of HCV RNA in saliva and salivary glands samples. Pearson's chi-squared and Fisher's exact tests were performed for statistical analysis. RESULTS: Anti-HCV antibodies could be detected in 47/180 (26.1%) saliva samples. In 11/47 (23.5%) of these, HCV RNA was also detected. From the 133/180 (73.9%) saliva samples with undetectable anti-HCV antibodies, 49/133 (36.8%) were positive for HCV RNA at least in one saliva sample. From the 64 patients from whom salivary gland samples were available, 17/64 (26.6%) had detectable anti-HCV antibodies in saliva, from which 2/17 (11.8%) also had HCV RNA in the salivary gland. From the 47/64 (73.4%) cases negative for anti-HCV antibodies in saliva, 10/47 (21.3%) were positive for HCV RNA in salivary gland. CONCLUSIONS: Taken together, our results suggest that there is no correlation between the presence of anti-HCV antibodies in saliva and the detection of HCV RNA in saliva and salivary glands in patients with chronic hepatitis C. Nevertheless, as there was a statistically significant difference between detection of anti-HCV antibodies and HCV RNA in stimulated saliva, our study points toward the need for new research on mechanisms of HCV shedding in saliva.

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin ± amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial.

INTRODUCTION: A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care(pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin. MATERIAL AND METHODS: Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (40KD) 180 µg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). RESULTS: The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. CONCLUSION: Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.

Dyspnoea in patients with chronic hepatitis C treated with pegylated interferon and ribavirin.

BACKGROUND: Adverse events attributed to the treatment of chronic hepatitis C patients with pegylated interferon (PEG-IFN) and ribavirin have been widely discussed. Lung disorders have been described, but the respiratory function of these patients during treatment has not been well studied. The aim of this study was to investigate the incidence of dyspnoea and possible changes in lung function associated with the use of PEG-IFN and ribavirin. METHODS: We evaluated clinical data and spirometry in 31 patients with chronic hepatitis C infections prior to treatment, in the 2(nd) week of treatment and in the 12(th) week of treatment. RESULTS: During the follow-up period, 19 patients (61.3%) had dyspnoea. Decreased haemoglobin levels were observed during the study, but there was no significant association with dyspnoea. However, patients with a body mass index (BMI) greater than 25 had a higher incidence of dyspnoea. No significant difference was detected between the values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), or forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio measured during the investigation. However, a significant decrease in FEV1 and FEV1/FVC ratio was observed in patients with later stages of liver fibrosis. CONCLUSIONS: Dyspnoea is a frequently occurring respiratory symptom during chronic hepatitis C treatment, and it is not associated with changes in spirometric parameters in the first 12 weeks of treatment. However, changes in FEV1 and FEV1/FVC can be observed in patients with advanced liver disease in the first 12 weeks of treatment with PEG-IFN and ribavirin.

Concerns regarding hepatitis B vaccination and post-vaccination test among Brazilian dentists.

BACKGROUND: Hepatitis B infection is the major cause of acute and chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide and has long been recognized as an occupational hazard among dentists. The aim of the present study was to examine factors associated to the self-reporting of hepatitis B vaccination and immunization status among dentists working in the city of Belo Horizonte, Brazil. METHODS: A cross-sectional survey was carried out with 1302 dentists in Belo Horizonte, Brazil. After signing a term of informed consent, the participants answered a structured questionnaire on their knowledge regarding their vaccination and immunization status against hepatitis B. Data on demographic, behavioural and occupational exposure aspects were also collected through questionnaires. RESULTS: The results revealed that 73.8% of the dentists reported having received three doses of the vaccine. Multivariate analysis revealed that gender (p = 0.006), use of individual protective equipment (p = 0.021), history of blood transfusion (p = 0.024) and history of illicit drug use (p = 0.013) were independently associated with vaccination against hepatitis B. Only 14.8% had performed a post-vaccination test. The use of individual protective equipment (p = 0.038), dentists who asked patients about hepatitis during dental treatment (p < 0.001), a family history of hepatitis B (p = 0.003) and work experience (p < 0.05) were independently associated with the post-vaccination test. CONCLUSIONS: Although there were a large number of vaccinated dentists in Belo Horizonte, the percentage was less than what was expected, as Brazil offers the National Program of Viral Hepatitis Vaccination, which provides free hepatitis B vaccinations to all healthcare workers. Despite being part of a high risk group for contamination, most of the dentists did not know their immunization status.

Factors associated with seroprevalence of hepatitis C among dentists at a large Brazilian city.

BACKGROUND: The aim of the present study was to investigate the seroprevalence and sociodemographic data, health-related and occupational factors and other correlates of sero-posivity among dentists in the city of Belo Horizonte, MG, Brazil. METHODS: A cross-sectional survey was carried out with 1302 dentists in Belo Horizonte, Brazil. All dentists were tested for anti-HCV using a commercially available enzyme-linked immunosorbent assay (ELISA). Individuals positive for anti-HCV were recalled for further evaluation. The presence of HCV RNA in anti-HCV-positive samples was assessed using reverse transcription-polymerase chain reaction (RT-PCR). Data on demographic, behavioural and occupational exposure aspects were collected through questionnaires. RESULTS: The seroprevalence of anti-HCV was 0.9% (95% IC 0.5-1.7%). The factors associated to the prevalence of hepatitis C were history of blood transfusion (p = 0.002) and having undergone a test for hepatitis C (p = 0.015). CONCLUSIONS: The seroprevalence of anti-HCV among dentists is low. Moreover, no occupational exposure was associated to the seroprevalence of hepatitis C.

Exacerbation of oral lichen planus lesions during treatment of chronic hepatitis C with pegylated interferon and ribavirin.

It is estimated that 170-200 million people in the world are chronically infected with the hepatitis C virus. This fact indicates that the prevention and treatment of hepatitis C virus infection are a priority in public health care. To date, the best treatment consists of the combination of pegylated interferon (IFN) and ribavirin. IFN is costly and associated with low tolerance and severe side effects. Ribavirin is also problematic because it causes secondary anemia in most patients. It has been described that oral lichen planus (OLP) can appear or be exacerbated during the treatment of chronic hepatitis C. The improvement of the lesions of OLP after the discontinuation of therapy suggests that IFN may induce or worsen these lesions in some patients. This study examines three cases of exacerbation of OLP during the treatment of chronic hepatitis C with pegylated IFN and ribavirin.

Genetic variability in the 5' UTR and NS5A regions of hepatitis C virus RNA isolated from non-responding and responding patients with chronic HCV genotype 1 infection.

Sequence variation among different hepatitis C virus (HCV) isolates has adaptive significance and reflects the modes and intensities of selection mechanisms operating on the virus. In this work, we sought to investigate using classical population genetics parameters, the genetic variability of HCV genotype 1 using the 5' UTR and NS5A regions from treatment non-responding and responding groups of patients. Both regions showed low genetic variability and the 5' UTR showed neutral deviation. No differences were observed in the nonsynonymous/synonymous nucleotide substitution ratio among groups for NS5A. The analysis of molecular variance test of the 5' UTR region showed an 11.94% variation among groups. Phylogenetic analysis showed no correlation between sequence variations and therapeutic responses.

Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in HCV patients as a prototype to monitor immunotherapy of infectious diseases.

In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.

Secondary bronchiolitis obliterans organizing pneumonia during treatment of chronic hepatitis C: role of pegylated interferon alfa-2a.

The treatment of chronic hepatitis C has frequent side effects such as cytopenias and neuropsychiatric symptoms. However, pulmonary toxicity associated with interferon is rarely described. This paper describes the clinical case of a 67-year-old female patient with chronic hepatitis C who presented an acute onset of dry cough, dyspnoea, and fever 36 weeks after the use of pegylated interferon alfa-2a and ribavirin. The lung biopsy confirmed the diagnosis of a bronchiolitis obliterans organizing pneumonia (BOOP). Corticotherapy was initiated, with clinical and radiological improvement. This paper aims to advise physicians to this occasional, though severe, adverse event related to hepatitis C virus (HCV) treatment.

Detection of HCV RNA in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C.

OBJECTIVE: The objective of this study was to investigate the prevalence of hepatitis C virus (HCV) RNA in saliva and its possible association with xerostomia and hyposalivation in patients with chronic hepatitis C. STUDY DESIGN: One hundred and thirty-six patients with confirmed diagnosis of chronic hepatitis C were prospectively analyzed before HCV treatment. The prevalence of xerostomia and hyposalivation was clinically evaluated. HCV RNA was investigated in saliva samples by qualitative PCR test. Univariate and multivariate analyses were used to verify associations. RESULTS: Xerostomia was reported by 48 (35.3%) patients, whereas hyposalivation was observed in 26 (19.1%). HCV RNA was positive in the saliva of 53 (39.0%) patients. An association among HCV RNA-positive saliva with xerostomia or hyposalivation was not observed. CONCLUSION: Our results demonstrate that the detection of HCV in saliva does not correlate with salivary flow or xerostomia in patients with chronic hepatitis C.

Xerostomia, hyposalivation and sialadenitis in patients with chronic hepatitis C are not associated with the detection of HCV RNA in saliva or salivary glands.

OBJECTIVE: Salivary gland disorders in patients with chronic hepatitis C (CHC) have been considered oral extrahepatic manifestations, reinforcing the hepatitis C virus (HCV) as a sialotropic virus. Hence, the authors investigated the prevalence of HCV RNA in saliva and salivary glands and its possible association with xerostomia, hyposalivation and sialadenitis in patients with CHC. PATIENTS AND METHODS: In 65 patients with confirmed CHC, the HCV RNA was investigated by nested RT-PCR in saliva samples and minor salivary glands. Xerostomia, hyposalivation, clinical and histopathological evidence of sialadenitis were also evaluated. Univariate and multivariate analyses were employed to verify associations. RESULTS: HCV RNA was detected in the saliva of 26/65 (40.0%) patients and in 12/65 (18.5%) salivary glands. Xerostomia was reported by 23/65 (35.4%) patients, and hyposalivation was diagnosed in 13/65 (20.0%) patients. Sialadenitis was confirmed by histopathological features in 31/65 (47.7%) patients. Twelve (38.7%) of the 31 patients with sialadenitis presented HCV RNA in saliva and 2/31 (6.5%) in salivary glands. No associations were found between xerostomia, hyposalivation or sialadenitis and the detection of HCV RNA in saliva or in salivary glands. CONCLUSIONS: Although xerostomia, hyposalivation and sialadenitis are frequent findings in CHC patients, our study did not confirm the association between the detection of HCV RNA in saliva or salivary glands with these salivary gland disorders. However, an indirect role of HCV by immune-mediated virus mechanisms in the pathogenesis of salivary gland disorders in this group of patients cannot be ruled out.

Secondary bronchiolitis obliterans organizing pneumonia during treatment of chronic hepatitis C: role of pegylated interferon alfa-2a / Bronquiolite obliterante com pneumonia em organização durante o tratamento da hepatite crônica C: papel do interferon peguilado alfa-2a

The treatment of chronic hepatitis C has frequent side effects such as cytopenias and neuropsychiatric symptoms. However, pulmonary toxicity associated with interferon is rarely described. This paper describes the clinical case of a 67-year-old female patient with chronic hepatitis C who presented an acute onset of dry cough, dyspnoea, and fever 36 weeks after the use of pegylated interferon alfa-2a and ribavirin. The lung biopsy confirmed the diagnosis of a bronchiolitis obliterans organizing pneumonia (BOOP). Corticotherapy was initiated, with clinical and radiological improvement. This paper aims to advise physicians to this occasional, though severe, adverse event related to hepatitis C virus (HCV) treatment.

O tratamento da hepatite C crônica apresenta efeitos colaterais frequentes como citopenias e sintomas neuropsiquiátricos. Contudo, a toxicidade pulmonar associada ao interferon é raramente descrita. Relatamos o caso de uma paciente com 67 anos que apresentou início agudo de tosse, dispnéia e febre após 36 semanas de uso do interferon peguilado alfa-2a e ribavirina. A biópsia pulmonar confirmou o diagnóstico de bronquiolite obliterante com pneumonia em organização, com significativa melhora clínico-radiológica após instituída a corticoterapia. Este relato de caso visa alertar os médicos para a possibilidade desse ocasional, embora grave, evento adverso associado ao tratamento da hepatite C.

Hepatites virais na prática odontológica: riscos e prevenção / Viral hepatites in dental practice: risks and prevention

Objetivo: Discuti r os aspectos epidemiologicos das hepatites virais em profissionais de Odontologia, com enfase nas formas de transmissao e prevencao. Metodo: Revisao narrativa da literatura sobre riscos e prevencao das hepatites na pratica odontologica. Resultados: As hepatites constituem um grupo de doencas inflamatorias do figado de diversas etiologias, sendo mais comuns aquelas causadas pelos virus hepatotropicos de A a E. As hepatites A e E apresentam forma clinica aguda e autolimitada. As hepatites B e C podem cronificar e evoluir para a cirrose. Os sinais e sintomas das hepatites sao semelhantes e a evolucao da forma cronica e silenciosa ou oligossintomatica, sendo a doenca descoberta por acaso, muitas vezes em estagios avancados. O diagnostico precoce favorece maiores chances de cura. Os trabalhadores da area da saude tem maior risco de adquirirem hepatites principalmente pelos virus B e C. Conclusao: Os cirurgioes-dentistas, em sua pratica diaria, estao expostos a maior risco de acidentes com instrumentos perfuro-cortantes constituindo assim, um grupo de alto risco de contaminacao. E possivel que outros agentes causadores de diferentes formas de hepatites ou outras doencas, sejam identificados no futuro. A adocao de normas de precaucao universal no controle de infeccao e, e continuara sendo, fundamental para o controle das doencas transmissiveis no ambiente odontologico.

Objective: To discuss the epidemiological aspects of viral hepatites in dental professionals, with emphasis of the forms of transmission and prevention. Method: Narrative review of the literature on risks and prevention of the hepatites types in dental practice. Results: Hepatites are a group of inflammatory liver diseases with several etiologies, among which the most common are those caused by the A-E hepatotropic viruses. Hepatites A and E have acute and self-limited clinical presentation. Hepatites B and C may become chronic and progress to cirrhoses. The signs and symptoms of hepatites are similar and their evolution to the chronic form is silent or oligosymptomatic, which makes the disease being diagnosed incidentally, frequently at an advance stage. The early diagnosis increases the chances of chances of cure. Health professionals are at higher risk of having hepatites, especially those causes by the B and C viruses. Conclusion: Dentists, in their daily practice, are more exposed to accidents with cutting and perforating instruments, being thus a group with high risk of contamination. It is possible that other agents causing different forms of hepatitis or other diseases are identified in the future. The adoption of the universal infection control measures is and will always be essential for controlling transmissible diseases in dental facilities.

Hepatite C: uma revisão para dentistas / Hepatitis C: a review for dentists

Neste trabalho, os autores fazem uma revisão de literatura sobre a hepatite C ressaltando aspectos importantes da doença, tais como a epidemiologia, a virologia, a transmissão, o diagnóstico, a história natural, as manifestações extra-hepáticas, o tratamento e as manifestações bucais e sistêmicas relevantes para os cirurgiões-dentistas.

Genetic variability in the 5' UTR and NS5A regions of hepatitis C virus RNA isolated from non-responding and responding patients with chronic HCV genotype 1 infection

Sequence variation among different hepatitis C virus (HCV) isolates has adaptive significance and reflects the modes and intensities of selection mechanisms operating on the virus. In this work, we sought to investigate using classical population genetics parameters, the genetic variability of HCV genotype 1 using the 5' UTR and NS5A regions from treatment non-responding and responding groups of patients. Both regions showed low genetic varia-bility and the 5' UTR showed neutral deviation. No differences were observed in the nonsynonymous/synonymous nucleotide substitution ratio among groups for NS5A. The analysis of molecular variance test of the 5' UTR region showed an 11.94 percent variation among groups. Phylogenetic analysis showed no correlation between sequence variations and therapeutic responses.

Líquen plano bucal e hepatite C / Oral lichen planus and hepatitis C

O Líquen Plano bucal tem sido relacionado com o vírus da Hepatite C, com achados ainda inconclusivos, não estando, ainda estabelecida, se essa associação é real ou ocasional. Esse trabalho tem por objetivo revisar a literatura atual sobre a prevalência da relação entre o Líquen Plano bucal e a Hepatite C, com levantamento de dados e discussão crítica dos achados. Embora estudos surgiram uma asociação loco regional, a relação entre o Líquen Plano bucal e hepatite C não está, ainda totalmente estabelecida, sendo necessárias maiores investigações.