Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D.

In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espírito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espírito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.

Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors.

BACKGROUND: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. METHODS: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. RESULTS: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). CONCLUSIONS: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors

ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

SARS-CoV-2 infection prevalence and associated factors: a serial population-based study in Espírito Santo, Brazil, May to June 2020. / Prevalência e fatores associados à infecção por SARS-CoV-2: estudo de base populacional seriado, no Espírito Santo, de maio a junho/2020.

OBJECTIVE: To analyze SARS-CoV-2 seroprevalence and association of sociodemographic and clinical aspects in the state of Espírito Santo, Brazil. METHODS: This was a serial cross-sectional study carried out in four phases, using households as the unit of analysis, from May to June 2020. Eleven municipalities were surveyed, with a sample of 4,500 households in each phase. RESULTS: Prevalence ranged from 2.1% (95%CI 1.7;2.5) on May 10 (first phase) to 9.6% (95%CI 8.8;10.4) on June 21 (fourth phase). In the Greater Vitória Metropolitan Region, the prevalence were 2.7% (95%CI 2.2;3.3) in the first phase, and 11.5% (95%CI 10.5;12.6) in the fourth phase; in the interior region of the state, prevalence ranged from 0.4% (95%CI 0.1;0.9) to 4.4% (95%CI 3.2;5.5) between the two phases. CONCLUSION: The increase in SARS-CoV-2 seroprevalence found in the fourth phase highlighted the high transmission of the virus, information that can support management of the pandemic.

Hepatitis B virus genotypes and subgenotypes and the natural history and epidemiology of hepatitis B.

INTRODUCTION AND OBJECTIVES: Espírito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espírito Santo Hospital. MATERIALS AND METHODS: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+)  and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software. RESULTS: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES. CONCLUSIONS: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively.

Prevalência e fatores associados à infecção por SARS-CoV-2: estudo de base populacional seriado, no Espírito Santo, de maio a junho/2020 / Prevalencia y factores asociados a la infección por SARS-CoV-2: un estudio poblacional seriado en Espírito Santo, Brasil, de mayo a junio de 2020 / SARS-CoV-2 infection prevalence and associated factors: a serial population-based study in Espírito Santo, Brazil, May to June 2020

Objetivo: Analisar a soroprevalência de SARS-CoV-2 e sua associação com aspectos sociodemográficos e clínicos, no estado do Espírito Santo, Brasil. Métodos: Estudo transversal seriado, realizado em quatro fases, no período de maio a junho de 2020, utilizando os domicílios como unidade de análise. Foram pesquisados 11 municípios, com amostra de 4.500 domicílios em cada fase. Resultados: A soroprevalência de SARS-CoV-2 variou de 2,1% (IC95% 1,7;2,5), em 10 de maio (primeira etapa), a 9,6% (IC95% 8,8;10,4) em 21 de junho (quarta etapa). Na Região Metropolitana da Grande Vitória, as prevalências foram de 2,7% (IC95% 2,2;3,3), na primeira, e de 11,5% (IC95% 10,5;12,6) na quarta etapa; no interior do estado, a prevalência variou de 0,4% (IC95% 0,1;0,9) a 4,4% (IC95% 3,2;5,5) entre a primeira e a quarta etapas. Conclusão: O aumento da soroprevalência de SARS-CoV-2 observado na quarta fase destacou a elevada transmissão do vírus, informação que pode subsidiar a gestão da pandemia.

Objetivo: Analizar la seroprevalencia del SARS-CoV-2 y la asociación de aspectos sociodemográficos y clínicos en el estado de Espírito Santo, Brasil. Métodos: Estudio transversal seriado realizado en cuatro fases, utilizando los hogares como unidad de análisis, de mayo a junio de 2020. Se encuestaron 11 municipios, con una muestra de 4.500 hogares en cada fase. Resultados: La prevalencia varió de 2,1% (IC95% 1,7;2,5) el 10 de mayo (primera etapa) a 9,6% (IC95% 8,8;10,4), el 21 de junio (cuarta etapa). En la Región Metropolitana de la Gran Vitória, las prevalencias fueron de 2,7% (IC95% 2,2;3,3), en la primera, y de 11,5% (IC95% 10,5;12,6) en la cuarta etapa; en el estado osciló entre 0,4% (IC95% 0,1;0,9) y 4,4% (IC95% 3,2;5,5). Conclusión: El aumento de la seroprevalencia del SARS-CoV-2 observado en la cuarta fase destacó la alta transmisión del virus, información que puede subsidiar el manejo de la pandemia.

Objective: To analyze SARS-CoV-2 seroprevalence and association of sociodemographic and clinical aspects in the state of Espírito Santo, Brazil. Methods: This was a serial cross-sectional study carried out in four phases, using households as the unit of analysis, from May to June 2020. Eleven municipalities were surveyed, with a sample of 4,500 households in each phase. Results: Prevalence ranged from 2.1% (95%CI 1.7;2.5) on May 10 (first phase) to 9.6% (95%CI 8.8;10.4) on June 21 (fourth phase). In the Greater Vitória Metropolitan Region, the prevalence were 2.7% (95%CI 2.2;3.3) in the first phase, and 11.5% (95%CI 10.5;12.6) in the fourth phase; in the interior region of the state, prevalence ranged from 0.4% (95%CI 0.1;0.9) to 4.4% (95%CI 3.2;5.5) between the two phases. Conclusion: The increase in SARS-CoV-2 seroprevalence found in the fourth phase highlighted the high transmission of the virus, information that can support management of the pandemic.

Living conditions, seroprevalence and symptoms of COVID-19 in slums in the Metropolitan Region of Vitória (Espírito Santo).

OBJECTIVES: to estimate the prevalence of SARS-CoV-2 infection in residents of the Greater Vitória region living in subnormal and non-subnormal agglomerates, and to compare sociodemographic and clinical characteristics of total residents (infected and not infected with SARS-CoV-2) between them. METHODS: Population-based prevalence study conducted by serological testing in 2020, with a study unit in households in Greater Vitória, grouped into census tracts classified as sub-normal agglomerates and non-sub-normal agglomerates. The two groups were compared in terms of prevalence and associated factors. The significance level adopted was 5%. RESULTS: The prevalence found in the sub-normal clusters was 12.05% (95%CI 9.59-14.50), and in the non-sub-normal clusters 10.23% (95%CI 7.97-12.50) this difference was not statistically significant (p = 0.273). Comparing the sociodemographic characteristics, more people who declare themselves to be of mixed race were found in the sub-normal clusters, a higher percentage of illiterates and people with only elementary education, greater number of residents per household, longer stay in public transportation, sharing a bathroom with another household, fewer bedrooms per residence and higher frequency of irregular water supply when compared to non-sub-normal clusters (p < 0.05). CONCLUSIONS: The epidemiological characteristics of sub-normal clusters' residents show the social inequalities that can hinder control measures in a pandemic situation.

COVID-19 in children, adolescents and young adults: a cross-sectional study in Espírito Santo, Brazil, 2020. / COVID-19 em crianças, adolescentes e jovens: estudo transversal no Espírito Santo, 2020.

OBJECTIVE: To analyze self-reported sociodemographic and clinical characteristics among individuals aged 2 to 22 years and possible associations with SARS-CoV-2 infection in Espírito Santo, Brazil. METHODS: This was a serial cross-sectional population-based study carried out from May to June 2020. The COVID-19 positivity rate was assessed by serological testing, and associated factors were assessed using Pearson's chi-square test (5% significance level). RESULTS: Among 1,693 individuals aged 2 to 22 years, 6.1% tested positive for COVID-19 and, among these, 35.5% did not present any symptoms. Differences were identified between positive and negative cases regarding the number of symptoms (p-value=0.001).Coughing was reported by 40.4% of positive individuals. Only 14.3% sought health care, namely 29.8% among those who tested positive and 13.3% among those who tested negative (p-value=0.001). CONCLUSION: The percentage of asymptomatic patients can impact the COVID-19 transmission chain in schools and fuel outbreaks of the disease in schools.

Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1-6 in Brazil.

INTRODUCTION AND OBJECTIVES: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. PATIENTS AND METHODS: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. RESULTS: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. CONCLUSIONS: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219216.

Living conditions, seroprevalence and symptoms of COVID-19 in slums in the Metropolitan Region of Vitória (Espírito Santo) / Condições de vida, soro prevalência e sintomas de COVID-19 em favelas na Região Metropolitana de Vitória (Espírito Santo)

ABSTRACT: Objectives: to estimate the prevalence of SARS-CoV-2 infection in residents of the Greater Vitória region living in subnormal and non-subnormal agglomerates, and to compare sociodemographic and clinical characteristics of total residents (infected and not infected with SARS-CoV-2) between them. Methods: Population-based prevalence study conducted by serological testing in 2020, with a study unit in households in Greater Vitória, grouped into census tracts classified as sub-normal agglomerates and non-sub-normal agglomerates. The two groups were compared in terms of prevalence and associated factors. The significance level adopted was 5%. Results: The prevalence found in the sub-normal clusters was 12.05% (95%CI 9.59-14.50), and in the non-sub-normal clusters 10.23% (95%CI 7.97-12.50) this difference was not statistically significant (p = 0.273). Comparing the sociodemographic characteristics, more people who declare themselves to be of mixed race were found in the sub-normal clusters, a higher percentage of illiterates and people with only elementary education, greater number of residents per household, longer stay in public transportation, sharing a bathroom with another household, fewer bedrooms per residence and higher frequency of irregular water supply when compared to non-sub-normal clusters (p < 0.05). Conclusions: The epidemiological characteristics of sub-normal clusters' residents show the social inequalities that can hinder control measures in a pandemic situation.

RESUMO: Objetivo: Estimar prevalência de infecção pelo SARS-CoV-2 em residentes na região da Grande Vitória, moradores de aglomerados subnormais e não subnormais, e comparar características sociodemográficas e clínicas dos residentes totais (infectados e não infectados com o SARS-CoV-2), entre esses aglomerados. Métodos: Estudo de prevalência de base populacional, por meio de teste sorológico realizado em 2020, com unidade de estudo em domicílios da Grande Vitória, agrupados em setores censitários classificados como aglomerados subnormais e aglomerados não subnormais. Os dois grupos foram comparados quanto à prevalência e aos fatores associados. O nível de significância adotado foi de 5%. Resultados: A prevalência encontrada em não aglomerados subnormais foi 12,05% (IC95% 9,59-14,50) e no grupo aglomerados não subnormais foi 10,23% (IC95% 7,97-12,50), e essa diferença não foi estatisticamente significante (p = 0,273). Comparando-se as características sociodemográficas, encontraram-se nos aglomerados subnormais mais pessoas que se autodeclaram da raça/cor parda, percentual maior de analfabetos e de pessoas apenas com ensino fundamental, maior número de moradores por domicílio, maior permanência em transporte coletivo, compartilhamento de banheiro com outro domicílio, menos dormitórios por residência e maior frequência de abastecimento irregular de água quando comparado aos aglomerados não subnormais (p<0,05). Conclusões: As características epidemiológicas dos moradores de aglomerados subnormais evidenciam as desigualdades sociais que podem dificultar as medidas de controle em uma situação de pandemia.

COVID-19 em crianças, adolescentes e jovens: estudo transversal no Espírito Santo, 2020 / COVID-19 en niños, adolescentes y jóvenes: estudio transversal en Espírito Santo, Brasil, 2020 / COVID-19 in children, adolescents and young adults: a cross-sectional study in Espírito Santo, Brazil, 2020

Objetivo: Analisar aspectos sociodemográficos e clínicos autorreferidos entre indivíduos de 2 a 22 anos de idade e possíveis associações com infecção por SARS-CoV-2 no Espírito Santo, Brasil. Métodos: Estudo transversal seriado de base populacional, realizado de maio a junho de 2020. Avaliou-se o percentual de positividade para COVID-19, por teste sorológico, e os fatores associados pelo teste qui-quadrado de Pearson (nível de significância de 5%). Resultados: Entre 1.693 indivíduos de 2 a 22 anos, 6,1% apresentaram teste positivo para COVID-19; destes, 35,5% não apresentaram nenhum sintoma. Foram identificadas diferenças entre os soropositivos e soronegativos quanto ao número de sintomas (p-valor=0,001). A tosse foi relatada por 40,4% dos indivíduos soropositivos. Apenas 14,3% procuraram unidades de saúde, sendo 29,8% entre os soropositivos e 13,3% entre os soronegativos (p-valor=0,001). Conclusão: O percentual de indivíduos assintomáticos pode impactar a cadeia de transmissão da COVID-19 nas escolas, e impulsionar surtos da doença no mesmo ambiente escolar.

Objetivo: Analizar aspectos sociodemográficos y clínicos autoinformados en individuos de 2 a 22 años y posibles asociaciones con la infección por SARS-CoV-2 en Espírito Santo. Métodos: Estudio transversal seriado realizado de mayo a junio de 2020. El porcentaje de positividad para COVID-19 se evaluó mediante prueba serológica y los factores asociados mediante la prueba de chi-cuadrado de Pearson (significación del 5%). Resultados: Entre 1.693 individuos de 2 a 22 añoo, el 6,1% dio positivo para COVID-19 y, entre estos, el 35,5% no presentó ningún síntoma. Se identificaron diferencias entre seropositivo y seronegativo en cuanto al número de síntomas (p=0,001). El 40,4% de los seropositivos informaron tos. El 14,3% buscó asistencia sanitaria, el 29,8% entre los seropositivos y el 13,3% entre los seronegativos (p=0,001). Conclusión: El porcentaje de pacientes asintomáticos puede impactar la transmisión de COVID-19 en las escuelas y potenciar brotes de la enfermedad en el mismo ambiente.

Objective: To analyze self-reported sociodemographic and clinical characteristics among individuals aged 2 to 22 years and possible associations with SARS-CoV-2 infection in Espírito Santo, Brazil. Methods: This was a serial cross-sectional population-based study carried out from May to June 2020. The COVID-19 positivity rate was assessed by serological testing, and associated factors were assessed using Pearson's chi-square test (5% significance level). Results: Among 1,693 individuals aged 2 to 22 years, 6.1% tested positive for COVID-19 and, among these, 35.5% did not present any symptoms. Differences were identified between positive and negative cases regarding the number of symptoms (p-value=0.001). Coughing was reported by 40.4% of positive individuals. Only 14.3% sought health care, namely 29.8% among those who tested positive and 13.3% among those who tested negative (p-value=0.001). Conclusion: The percentage of asymptomatic patients can impact the COVID-19 transmission chain in schools and fuel outbreaks of the disease in schools.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B.

Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified. Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment. The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc). Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Hepatite C no sistema público de saúde brasileiro: impacto da doença / Hepatitis c in the brazilian public health care system: burden of disease

ABSTRACT BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é uma das principais causas de hepatite C crônica e provoca implicações graves para pacientes, familiares e sistema de saúde. OBJETIVO: Os objetivos deste estudo foram: analisar a gravidade da fibrose hepática, comorbidades e complicações da hepatite C; examinar a qualidade de vida relacionada à saúde (QVRS), a perda de produtividade e o uso de recursos e custos no sistema público por pacientes brasileiros com hepatite C crônica, genótipo tipo 1. MÉTODOS: Foi realizado um estudo transversal, multicêntrico em pacientes com hepatite C crônica genótipo-1 para avaliar a carga da doença no sistema público de saúde brasileiro entre novembro de 2014 e março de 2015. Os pacientes foram submetidos a uma elastografia hepática transitória (FibroScan) para avaliar a fibrose e a uma entrevista composta por um questionário desenvolvido para o estudo e cinco questionários padronizados: EQ-5D-3L, HCV-PRO, e WPAI:HepC. RESULTADOS: Foram recrutados 313 pacientes. A amostra foi composta predominantemente por mulheres (50,8%), caucasianos/brancos (55,9%) e indivíduos empregados (39,9%). A média de idade foi 56 (DP=10,4) anos. Em média, os pacientes com HCV esperaram 40,6 (DP=49,6) meses entre o diagnóstico e o primeiro tratamento. Ademais, 42,8% dos pacientes que realizaram o FibroScan tinham cirrose; a comorbidade mais frequente foi doença cardiovascular (62,6%) e a complicação mais comum as varizes esofágicas (54,5%). Os resultados também mostraram que "dor e desconforto" foi a dimensão de QVRS mais afetada (55,0% dos pacientes relataram alguns problemas) e que a média do escore do HCV-PRO foi 69,1 (DP=24,2). Em relação à perda de produtividade, o componente do WPAI:HepC mais afetado foi atividade diária (23,5%) e entre os pacientes empregados, presenteísmo foi mais frequente do que absenteísmo (18,5% vs 6,5%). Os custos diretos médicos totais com essa amostra foi de 12.305,72USD por paciente em um período de dois anos; o tratamento medicamentoso representou 95% desse total. CONCLUSÃO Esse estudo mostrou a maioria dos pacientes possui cirrose, apresenta alta prevalência de doenças cardiometabolicas e varizes esofágicas, QVRS reduzida principalmente em termos de dor/desconforto e dano na produtividade, especialmente presenteísmo. Adicionalmente, nós demonstramos que o HCV impõe uma carga econômica no sistema de saúde brasileiro e que os medicamentos correspondem à maioria dos custos.

HEPATITIS C IN THE BRAZILIAN PUBLIC HEALTH CARE SYSTEM: BURDEN OF DISEASE.

BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus.

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10; p<0.001) and occurrence of liver cirrhosis (PR 2.06; 95% CI 1.11-3.83; p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study.

OBJECTIVE:: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS:: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS:: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION:: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study

Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: ...

The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study.

INTRODUCTION: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. AIMS: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. METHODS: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. RESULTS: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with Peg-IFN and RBV were: absence of an AIDS-defining illness (p=0.001), HCV viral load lower than 600,000IU/mL at the onset of treatment (p=0.003), higher liver enzyme levels (p=0.039) at baseline, infection with genotypes 2 or 3 (p=0.003), and no transient treatment interruption (p=0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. CONCLUSIONS: in our Brazilian case series, the SVR rate under current clinical practice conditions was similar to that reported in other studies. There was a correlation between an SVR and being infected by genotypes 2 and 3, low viral load, high ALT levels at the onset of treatment, and absence of an AIDS-defining illness. Cytopenia and psychiatric disorders were the major causes of treatment interruption. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment.