Prevalencia de vacunación completa para la hepatitis B en el personal de salud de tres grandes hospitales generales del Paraguay / Prevalence of complete vaccination for hepatitis B in health personnel of three large general hospitals in Paraguay

Introducción: El personal de salud constituye un grupo de riesgo para la infección por el virus de las hepatitis B. Objetivos: Evaluar la frecuencia de vacunación contra Hepatitis B en profesionales médicos y de enfermería de tres grandes centros hospitalarios del Departamento Central de Paraguay. Materiales y métodos: Estudio cuantitativo, observacional, descriptivo, de corte transversal. Se aplicó un cuestionario al personal médico y de enfermería en estudio, elaborado según trabajos afines. Resultados: Fueron encuestadas 1097 personas, siendo médicos 412 (37.6%) yersonal de enfermería 685 (62.4%). Se encontró un nivel de vacunación completa del 48.2% sobre el total de encuestados, 49.5% de los varones presentaron esquema completo y 47.7% de las mujeres. Según la profesión, el personal de enfermería tiene mejor acatamiento con 51% de vacunación completa contra 47% del personal médico. En el Hospital Central del Instituto de Previsión Social, casi un 62% tenía esquema completo, el Hospital de Clínicas alcanzó 40.9% y solamente 36.6% de los encuestados del Hospital Nacional de Itauguá tenían todas las dosis de vacuna anti-Hepatitis B. Para riesgo biológico bajo, el nivel de vacunación completa fue del 36.0%, alcanzó el 36.8% para riesgo moderado y 57.3% para los de alto riesgo de exposición. Conclusión: Ante la baja prevalencia de vacunación completa contra Hepatitis B en el personal de salud, esta debe mejorarse considerando el riesgo biológico de exposición. El equipo de control de infecciones y el Departamento de salud laboral deben llevar un registro de vacunación del personal y tener un plan de inmunizaciones obligatorio.

Introduction: Health care personnel constitute a risk group for hepatitis B virus infection. Objectives: To evaluate the frequency of vaccination against Hepatitis B in medical and nursing professionals of three large hospital centers in the Central Department of Paraguay. Materials and methods: Quantitative, observational, descriptive, cross-sectional, cross-sectional study. A questionnaire was administered to medical and nursing personnel included in the study, based on related studies. Results: A total of 1097 people were surveyed, 412 (37.6%) were physicians and 685 (62.4%) were nurses. In general, a complete vaccination level of 48.2% of the total respondents was reached, 49.5% of men had a complete vaccination schedule and 47.7% of women. According to profession, the nursing staff had a better compliance with complete vaccination with 51% versus 47% of the medical staff. In the Hospital Central del Instituto de Previsión Social almost 62% had a complete schedule, the Hospital de Clínicas reached 40.9% and only 36.6% of the respondents of the Hospital Nacional de Itauguá had all the doses of anti-Hepatitis B vaccine. For low biological risk, the level of complete vaccination was 36.0%, reaching 36.8% for moderate risk and 57.3% for those at high risk of exposure. Conclusion: The level of complete vaccination against Hepatitis B in health personnel was low and should be improved, taking into account the biological risk of exposure. The infection control team and the occupational health department should keep a record of staff vaccination and have a mandatory immunization plan for it.

Hidrotórax hepático como complicación poco frecuente de la cirrosis. Un reto terapéutico en cirrosis avanzada / Hepatic hydrothorax as a rare complication of cirrhosis. A therapeutic challenge in advanced cirrhosis

El hidrotórax hepático es una entidad poco frecuente en pacientes con cirrosis. A la fecha se han propuesto varias alternativas terapéuticas, tanto médicas como quirúrgicas, previas al trasplante hepático como manejo definitivo. A continuación, se presenta el caso de una paciente de 78 años con cirrosis secundaria a infección por virus de la hepatitis C, que acudió al servicio de urgencias por dificultad respiratoria, donde se documentó un derrame pleural derecho masivo de tipo trasudado, que respondió parcialmente a terapia diurética e inserción de dren pleural; posteriormente falleció por complicaciones hemorrágicas asociadas a la cirrosis. Se considera importante describir esta patología, dada su baja frecuencia en pacientes con cirrosis y los retos terapéuticos a los que nos enfrentamos con la poca evidencia disponible en la actualidad.

Hepatic hydrothorax is a rare entity in patients with cirrhosis. To date, several therapeutic alternatives have been proposed, both medical and surgical, prior to liver transplantation as the definitive management. Here we present the case of a 78-year-old patient with cirrhosis secondary to hepatitis C virus infection, who consulted the emergency department for respiratory distress, documenting a massive right pleural effusion of transudate type, which responded partially to diuretic therapy and drainage with pigtail, and later died due to hemorrhagic complications associated with cirrhosis. It is important to describe this pathology given its low frequency in patients with cirrhosis and the therapeutic challenges we face with the limited currently available evidence.

Design of Inhibitory Peptides of the Interaction between the E2 Protein of the Hepatitis C Virus and the CD81 and CD209 receptors / Diseño de péptidos inhibitorios de la interacción entre la proteína E2 del virus de Hepatitis C y los receptores CD81 y CD209

Abstract Infection through the Hepatitis C virus does not have a vaccine and treatment with pegylated interferon and ribavirin can fail; which is why it may cause chronic infection and, consequently, could develop liver failure or hepatocellular carcinoma. It has been described that virus-cell recognition occurs between the E2 viral envelope protein and diverse cell receptors, with this interaction being critical in viral infection. which is why the study sought to identify inhibitory peptides of the interaction between viral E2 protein and the CD81 and CD209 receptors. Methodology: Through the RCSB protein database, crystals from the CD81 and CD209 receptors were selected, CD81/E2-HCV, CD209/E2-HCV complexes were carried out by SWISS-MODEL to generate inhibitory peptides of protein interaction through the Rosetta web server, this interaction was validated through ClusPro and finally, determined the theoretical physicochemical and cytotoxic properties of these peptides. Results: two peptides were obtained, without predicted toxicity, with a theoretical capacity of blocking the protein interaction between the E2 protein of the virus and CD81 and CD209.

Resumen La infección por el virus de la hepatitis C, no cuenta con vacuna y el tratamiento con interferón pegilado y ribavirina puede fallar; por lo que puede causar infec ción crónica y como consecuencia podría desarrollarse falla hepática o carcinoma hepatocelular. Se ha descrito que el reconocimiento virus-célula, se da entre la proteína de envoltura viral E2 y diversos receptores celulares, siendo esta interacción crítica en la infección viral. Razón por la cual este estudio buscó identificar péptidos inhibidores de la interacción entre la proteína E2 viral y los receptores CD81 y CD209. Metodología: A través de la base de datos de proteínas RCSB, se seleccionaron cristales de los receptores CD81 y CD209, se realizaron complejos CD81/E2-HCV, CD209/E2-HCV para generar péptidos inhibidores de interacción proteica a través del servidor web Rosetta, esta interacción fue validada a través de ClusPro y finalmente se evaluaron las propiedades fisicoquímicas y citotóxicas teóricas para estos péptidos. Resultados: se obtuvo dos péptidos, sin toxicidad predicha, con capacidad teórica de bloquear la interacción proteica entre la proteína E2 del virus y CD81 y CD209.

Increasing hepatitis virus screening uptake at worksites in Japan using nudge theory and full subsidies

BACKGROUND@#Despite the importance of hepatitis screening for decreasing liver cancer mortality, screening rates remain low in Japan. Previous studies show that full subsidies increase screening uptake, but full subsidies are costly and difficult to implement in low-resource settings. Alternatively, applying nudge theory to the message design could increase screening at lower costs. This study examined the effects of both methods in increasing hepatitis virus screening rates at worksites.@*METHODS@#1496 employees from a Japanese transportation company received client reminders for an optional hepatitis virus screening before their general health checkups. Groups A and B received a client reminder designed based on the principles of "Easy" and "Attractive," while the control group received a client reminder not developed using nudge theory. Additionally, hepatitis virus screening was offered to the control group and group A for a co-payment of JPY 612, but was fully subsidized for group B. The hepatitis virus screening rates among the groups were compared using a Chi-square test with Bonferroni correction, and the risk ratios of group A and group B to the control group were also calculated. To adjust for unobservable heterogeneity per cluster, the regression analysis was performed using generalized linear mixed models.@*RESULTS@#The screening rate was 21.2%, 37.1%, and 86.3% for the control group, group A, and group B, respectively. And the risk ratio for group A was 1.75 (95% confidence interval [CI] 1.45-2.12) and that of group B was 4.08 (95% CI 3.44-4.83). The parameters of group A and group B also were significant when estimated using generalized linear mixed models. However, the cost-effectiveness (incremental cost-effectiveness ratio (ICER)) of the nudge-based reminder with the full subsidies was lower than that of only the nudge-based reminder.@*CONCLUSIONS@#While fully subsidized screening led to the highest hepatitis screening rates, modifying client reminders using nudge theory significantly increased hepatitis screening uptake at lower costs per person.

Aproximación para establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes infectados con virus de hepatitis C, revisión estructurada (actualización 2015-2017) / Structured review of establishing and evaluating clinical relevance of drug interactions in hepatitis C virus treatment (Update 2015 - 2017)

Resumen Objetivo: establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes con hepatitis C. Método: se realizó una búsqueda en PubMed/MedLine de artículos publicados en inglés y en español, desde el 1 de enero de 2015 hasta el 30 de marzo de 2017, utilizando los términos Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, de estudios realizados en humanos. La relevancia clínica de las interacciones medicamentosas se estableció y evaluó con base en la probabilidad de ocurrencia y la gravedad de la interacción. Resultados: se identificaron 184 artículos, de los cuales 92 se seleccionaron por el título y resumen para revisión completa, a 2 de ellos no fue posible acceder al texto completo. De estos, 57 aportaban interacciones, lo que permitió identificar 155 parejas de interacciones medicamentosas, de las cuales 154 (99,4 %) fueron farmacocinéticas y 1 (0,6 %) farmacodinámica. Por su parte, de las 155 parejas, 34 (21,9 %) se valoraron de nivel 1; 73 (47,1 %) de nivel 2; 48 (31,0 %) de nivel 3; y 0 (0,0 %) de nivel 4. Además, se identificaron 29 parejas agrupadas como interacciones con evidencia de ausencia de relevancia clínica. Conclusiones: más de 99 % de las interacciones medicamentosas de relevancia clínica son farmacocinéticas, asociadas con cambios en el metabolismo y el transporte de fármacos; el simeprevir y la terapia 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) fueron los medicamentos con mayor número de interacciones.

Abstract Objective: This study-s objective is to establish and evaluate the clinical relevance of drug interactions during treatment of patients with hepatitis C. Method: A PubMed/MedLine search was conducted for articles published in English and Spanish from January 1, 2015 to March 30, 2017 using the terms Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, from studies conducted in humans. The clinical relevance of drug interactions was established and evaluated based on probability of occurrence and severity of interactions. Results: Of the 184 four articles identified, 92 were selected by title and abstract for full review. The full texts of two articles could not be accessed. Of the remaining articles, 57 describ ed relevant interactions. Of the 155 pairs of drugs that interact that were identified, 154 (99.4%) were pharmacokinetic, and one (0.6%) was pharmacodynamic. Thirty-four of the 155 pairs (21.9%) were assessed at level 1; 73 (47.1%) were assessed at level 2; 48 (31.0%) were assessed at level 3, none were assessed at level 4. In addition, 29 pairs of interacting drugs had no evidence of clinical relevance. Conclusions: More than 99% of clinically relevant drug interactions are pharmacokinetics and are associated with changes in metabolism and transport of drugs. Simeprevir and 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) therapy had the greatest number of interactions.

Hepatobiliary Manifestation of Inflammatory Bowel Disease / 대한소화기병학회잡지

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Hepatobiliary Manifestation of Inflammatory Bowel Disease / 대한소화기학회지

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Prevalence and associated risk factors of Hepatitis B and C virus infections among mothers in Jimma, South West Ethiopia: a community-based study

Background: Viral hepatitis affects over 400 million people globally with 6 to 10 million people newly infected each year. Viral hepatitis infectious agents such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the greatest threats to the liver and can cause liver cancer. One of the most important modes of transmission of these viruses is a vertical transmission from mother to child. The aim of this study is to assess the prevalence of HBV and HCV infection as well as its associated risk factors among mothers in Jimma. Methods: A community-based cross-sectional study was conducted among 455 mothers in Jimma from June to December 2016. Simple random sampling was employed to recruit study participants and informed consent was obtained. From each mother, about 5ml of blood was collected and tested for HBsAg, anti-HBc, and HCVAg/Ab using ELISA. Chi-square and logistic regression tests were used to assess statistically significant associations between dependent and independent variables. P-values less than 0.05 were considered statistically significant. Result: HBsAg, anti-HBc and HCVAg/Ab prevalence was 5.7%, 30.5% and 2.5%, respectively. Multivariate logis-ic regression analysis showed that history of hospital admission (AOR = 3.098; P <0.040) and abortion (AOR = 15.514, P <0.001) remained independent predictors of HBsAg seropositivity. Conclusion: Hospital admission and abortion are the major risk factors for hepatitis B and C virus infection among mothers. Awareness creation for adult HBV vaccine and health education on modes of transmission should be promoted and strengthened

Metagenomic analysis reveals Hepatitis A virus in suspected yellow fever cases in Brazil

Using a metagenomic approach, we identified hepatitis A virus among cases of acute febrile illnesses that occurred in 2008-2012 in Brazil suspected as yellow fever. These findings reinforce the challenge facing routine clinical diagnosis in complex epidemiological scenarios.

Ledipasvir associado a sofosbuvir para o tratamento de pacientes adultos com hepatite C crônica infectados por vírus de genótipo 1 / Ledipasvir associated with sofosbuvir for the treatment of adult patients with chronic hepatitis C infected with genotype 1 virus

CONTEXTO: O objetivo do presente relatório é analisar as evidências científicas apresentadas pelo demandante no que diz respeito à associação entre ledipasvir e sofosbuvir (LDV/SOF) ser eficaz e segura para tratamento da hepatite C crônica, de acordo com desfechos como SVR12 (Resposta Virológica Sustentada - do inglês - Sustained Virological Response 12 weeks after the end of treatment) e 24, frequência de eventos adversos e descontinuação do tratamento pelos mesmos, visando avaliar a sua incorporação no SUS. TECNOLOGIA: Ledipasvir/sofosbuvir (Harvoni®). INDICAÇÃO: Pacientes adultos com infecção crônica pelo vírus da hepatite C (HCV ­ do inglês: Hepatitis C Virus), genótipo 1. PERGUNTA: O uso de ledipasvir/sofosbuvir (LDV/SOF) é eficaz, seguro e custo-efetivo em pacientes com infecção crônica pelo HCV genótipo 1, quando comparado a outras opções atualmente disponíveis no SUS para o tratamento? EVIDÊNCIAS CIENTÍFICAS: Foram incluídos 28 estudos avaliando a tecnologia LDV/SOF em pacientes com HCV GT 1. As evidências encontradas apresentaram qualidade baixa a moderada para eficácia e baixa a muito baixa para segurança, sendo a maioria de não inferioridade e/ou superioridade à taxa histórica de resposta ao tratamento e apontam para uma eficácia superior a 90,0% na maioria dos estudos. Dessa forma, os resultados encontrados para LDV/SOF apresentaram semelhança quanto à eficácia terapêutica quando comparados a outros antivirais disponíveis atualmente no SUS. Quanto ao perfil de segurança, os eventos adversos (EA) mais comumente relatados foram diarreia, náuseas, fadiga e cefaleia. Por fim, observou-se que a associação de LDV/SOF à ribavirina pode levar ao aumento de EA quando comparado à LDV/SOF apenas. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O demandante conduziu uma avaliação de custo-minimização, cujo modelo foi considerado adequado. Os custos considerados na análise foram restritos aos de aquisição dos diferentes medicamentos. O demandante propôs o valor de U$ 3.690,00 para a incorporação do tratamento com LDV/SOF. Foram considerados 65.000 tratamentos para Hepatite C, sendo o número de pacientes elegíveis para o tratamento com LDV/SOF de 41.600 pacientes. Considerou-se um Market Share de 30%. Assumiu-se dois cenários, um com todos os pacientes utilizando as alternativas terapêuticas de maior preço e o outro com as de menor preço. Dessa forma, com a incorporação de LDV/SOF no SUS, estima-se uma economia entre 60 e 80 milhões de reais no primeiro ano após a sua incorporação e não os 142 a 380 milhões apresentados pelo demandante. Em um horizonte temporal de cinco anos, o impacto orçamentário incremental seria uma economia entre 303 e 400 milhões. CONSIDERAÇÕES FINAIS: Os estudos incluídos neste relatório demonstram que o tratamento com LDV/SOF resultou em taxas de SVR12 altas, a maioria acima de 90%. Tanto a eficácia/efetividade, quanto o perfil de segurança se mostraram semelhantes aos dos demais medicamentos já incorporados no SUS. A avaliação econômica demonstrou que o tratamento com LDV/SOF poderá representar uma economia de 60 a 80 milhões de reais no primeiro ano de incorporação, comparado aos tratamentos atualmente disponíveis. RECOMENDAÇÃO INICIAL DA CONITEC: Na 63ª reunião ordinária da CONITEC em 1º de fevereiro de 2018 a Comissão decidiu por unanimidade emitir a recomendação inicial para a incorporação ao SUS da associação entre sofosbuvir 400 mg e ledipasvir 90 mg em comprimido único para o tratamento de hepatite C crônica em adultos causada exclusivamente pelo genótipo 1 do vírus. CONSULTA PÚBLICA: A consulta pública nº 10/2018 foi realizada entre os dias 24/02/2018 e 05/03/2018. Foram recebidas 29 contribuições, sendo 6 pelo formulário para contribuições técnico-científicas e 23 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação das contribuições encaminhadas pela consulta pública, o plenário da CONITEC entendeu que não houve argumentação suficiente para alterar sua recomendação inicial, mantendo-se a recomendação favorável à incorporação da associação dos antivirais sofosbuvir e ledipasvir para o tratamento de hepatite C crônica em adultos infectados pelo genótipo 1 do vírus. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 64ª reunião ordinária, no dia 08 de março de 2018, deliberaram, por unanimidade, por recomendar a incorporação ao SUS da associação dos antivirais sofosbuvir e ledipasvir para o tratamento de hepatite C crônica em adultos infectados pelo genótipo 1 do vírus. Foi assinado o registro de deliberação n° 345/2018 pela incorporação da tecnologia. DECISÃO: Incorporar o ledipasvir associado a sofosbuvir para o tratamento de pacientes adultos com hepatite C crônica infectados por vírus de genótipo 1, conforme Protocolo Clínico e Diretrizes Terapêuticas no âmbito do Sistema Único de Saúde - SUS, dada pela Portaria nº 12, publicada no DOU nº 51, do dia 15 de março de 2018, seção 1, pág. 59.(AU)

Recognition criteria for occupational cancers in relation to hepatitis B virus and hepatitis C virus in Korea

The goal of this study was to review the scientific basis for the recognition of occupational cancer, in relation to hepatitis viral infections in Korea. Most Hepatitis B virus (HBV) infections in Korea occur as vertical infections, but these are decreasing rapidly due to vaccination. Hepatitis C virus (HCV) is known to be transmitted through parenteral routes, but the transmission route is often unclear. Most occupational infections of hepatitis virus involve accidental injuries of medical institution workers while using virus-contaminated medical devices. Many cohort studies and case-control studies have consistently reported that HBV and HCV infection increases the risk of hepatocellular carcinoma (HCC) and the strength of this association is high. Non-Hodgkin's lymphoma appears to be associated with HCV. Cholangiocarcinoma, pancreatic cancer, leukemia, and thyroid cancer are considered to be less related or unrelated to epidemiological causation. There are no uniform international specific criteria for occupational cancer caused through occupational exposure to a hepatitis virus. In establishing appropriate standards applicable to Korea, there should be sufficient consideration of latency, virus exposure levels and frequency, and other cancers, apart from HCC. In conclusion, we recommend keeping the current specific criteria. However, if a worker is injured at work when using a sharp medical device, and HBV and HCV viral infections are confirmed through serologic tests; if the worker is diagnosed as having a chronic HBV or HCV infection, a subsequent HCC (or Non-Hodgkin's lymphoma following chronic HCV infection) can then be considered highly related to the worker's occupation.

Seroepidemiology of Hepatitis Viruses and Hepatitis B Genotypes of Female Marriage Immigrants in Korea

PURPOSE: The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. MATERIALS AND METHODS: Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. RESULTS: Subjects' median age was 33 years (20–40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). CONCLUSION: Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

Estudo da relação entre polimorfismos genéticos e hipermetilação de promotores gênicos e a progressão da hepatite crônica e desenvolvimento de carcinoma hepatocelular / Study of the relationship between genetic polymorphisms and hypermethylation of gene promoters and the progression of chronic hepatitis and the development of hepatocellular carcinoma

O carcinoma hepatocelular (CHC) é o segundo tipo de câncer mais letal no mundo. Os principais agentes etiológicos para o CHC são os vírus da hepatite B (HBV) e da hepatite C (HCV). A hepatocarcinogênese é um processo de múltiplas etapas afetado por fatores genéticos e epigenéticos. O papel de diferentes genes, como GSTT1, GSTM1, TP53, MDM2, RASSF1A e DOK1, tem sido avaliado nesse processo. Estudos tem observado a associação de polimorfismos genéticos e da hipermetilação de regiões promotoras de genes com o desenvolvimento do CHC. Entretanto, poucos estudos analisaram pacientes brasileiros até o momento. Os objetivos deste estudo foram avaliar se a ocorrência de polimorfismos genéticos e da hipermetilação de DNA estão associados à progressão da doença hepática e o desenvolvimento de cirrose e carcinoma hepatocelular (CHC) em pacientes brasileiros com hepatite crônica. Os polimorfirmos GSTT1 nulo (deleção), GSTM1 nulo (deleção), TP53 R72P (rs1042522) e MDM2 T309G (rs2279744) foram genotipados por PCR multiplex ou PCR seguida por análise do polimorfismo dos fragmentos de restrição (PCR-RFLP) em 190 pacientes (60 com CHC, 83 com cirrose e 47 com apenas hepatite crônica)Os níveis de metilação dos promotores dos genes RASSF1A e DOK1 foram medidos por pirosequenciamento de DNA extraído de 41 amostras de tecidos de fígado conservadas em parafina (20 de CHC, 9 de cirrose e 12 de hepatite crônica), após tratamento com bisulfito de sódio e amplificação das regiões específicas por PCR. Nossos resultados demostraram que a ocorrência do genótipo polimórfico nulo para o gene GSTT1, em pacientes crônicos para a hepatite C, está associado à progressão da doença hepática para cirrose e indiretamente ao desenvolvimento de CHC (p = 0,032). Observamos também que a ocorrência do perfil genotípico simultâneo GSTT1 nulo e TP53 Pro/Pro, o perfil genotípico simultâneo GSTM1 nulo e TP53 Arg/Arg, além do perfil genotípico simultâneo GSTM1 nulo, MDM2 T/T e TP53 Arg/Arg, em pacientes crônicos para a hepatite C, estão associados ao desenvolvimento de CHC (p < 0,050). Além disso, os níveis de metilação de DNA nos promotores dos genes DOK1 e RASSF1A, em tecido hepático, foram associados a progressão da doença hepática, sendo encontrados níveis baixos em tecidos não cirróticos, intermediários em tecidos cirróticos e elevados em tecidos de CHC. Este é um estudo pioneiro no Brasil e contribui para a identificação de fatores genéticos e epigenéticos que poderão ser utilizados futuramente para a seleção de pacientes com hepatite crônica em alto risco para o desenvolvimento do CHC. (AU)

Human Immunodeficiency Virus (HIV) and Hepatitis Virus Coinfection among HIV-Infected Korean Patients: The Korea HIV/AIDS Cohort Study

BACKGROUND: Despite declines in mortality and morbidity rates of patients with human immunodeficiency virus (HIV) infection as the result of highly active antiretroviral therapy, liver diseases due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a leading cause of death among HIV-infected patients. However, HIV and HBV or HCV coinfection is still poorly documented, and more information is needed to better understand the characteristics of HIV-infected patients in Korea. MATERIALS AND METHODS: A cross-sectional study was performed to investigate clinical characteristics and prevalence of HBV and HCV infection in HIV patients enrolled in the Korea HIV/acquired immune deficiency syndrome (AIDS) cohort study from 17 institutions between December 2006 and July 2013. RESULTS: Among the 1,218 HIV-infected participants, 541 were included in this study. The prevalence of HBV-HIV and HCV-HIV coinfection was 5.0% (27/541) and 1.7% (9/541), respectively. There was no patient who was positive for both HBs antigen and HCV antibody. In multivariate logistic regression analysis, HBV unvaccinated status was a significant risk factor for HBV-HIV coinfection (odds ratio = 4.95, 95% confidence interval = 1.43–17.13). CONCLUSIONS: HBV and HCV infection was more common in HIV-infected persons enrolled in the Korean HIV/AIDS cohort, than in the general population in Korea.

Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis

BACKGROUND/AIMS: Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. METHODS: The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. RESULTS: Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. CONCLUSIONS: Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.

Evidencia de circulación del virus de la hepatitis A, subgenotipo IA, en muestras ambientales en Antioquia, Colombia / Evidence of the circulation of hepatitis A virus, subgenotype IA, in environmental samples from Antioquia, Colombia

Introducción. El virus de la hepatitis A (HAV) es un importante patógeno que se transmite por vía fecal-oral. La epidemiología de la infección está directamente relacionada con el acceso de la población al agua potable y con la infraestructura de alcantarillado. Objetivo. Determinar la presencia del HAV e identificar el genotipo en muestras de agua de abastecimiento y agua residual en ocho municipios, un corregimiento y una vereda del departamento de Antioquia, noroccidente de Colombia. Materiales y métodos. Se hicieron tres muestreos seriados de diciembre de 2012 a abril de 2014 en la fuente principal de abastecimiento de los acueductos y en el principal vertimiento de aguas residuales de cada municipio. Las muestras se concentraron por filtración y ultrafiltración tangencial, y por las técnicas de polietilenglicol y floculación con leche descremada, respectivamente. A partir del ARN total de cada muestra, se amplificaron la región VP3-VP1 para la detección del genoma viral y la región VP1-2B para la genotipificación. Resultados. El genoma del HAV se detectó en las fuentes de agua de abastecimiento de Puerto Berrío, Frontino y Nutibara, y en las muestras de aguas residuales provenientes de los municipios de Arboletes, Zaragoza y Venecia. Mediante el análisis de las secuencias se identificó el subgenotipo IA del virus. Conclusión. Este estudio permitió detectar la presencia del HAV en 6,6 % de las muestras de agua de abastecimiento y en 13,3 % de las muestras de agua residual de los municipios en estudio. Se reporta por primera vez la circulación del subgenotipo IA en muestras ambientales en Antioquia.

Introduction: Hepatitis A virus (HAV) is an important pathogen, typically transmitted via the faecal-oral route. The epidemiology of the infection is directly related to drinking water access and adequate disposal of sewage water. Objective: To determine the presence and identify the genotype of HAV in environmental samples from eight municipalities and two villages in Antioquia, northwestern Colombia. Materials and methods: Three serial samplings were done between December, 2012, and April, 2014. Water samples were obtained from drinking water plants prior to treatment, as well as from the main reserve of wastewater in each municipality included in the study. Viral concentrations for the two types of sample sources were determined by filtration/tangential ultrafiltration and polyethyleneglycol plus flocculation with skimmed milk, respectively. Total ARN was subsequently obtained from each sample and the VP3-VP1 region amplified for detection of the viral genome. The genotype was determined by amplification of the VP1-2B region. Results: The HAV genome was detected in samples from drinking water plants at Puerto Berrío, Frontino and Nutibara, and in wastewater samples from the municipalities of Arboletes, Zaragoza and Venecia. HAV subgenotype IA was identified using phylogenetic analysis. Conclusion: In this study, HAV was identified in 6.6% of the samples from drinking water plants and 13.3% of wastewater samples. This is the first report of HAV subgenotype IA circulating in environmental samples from Antioquia.

Aspectos clínicos-laboratoriais, perfil de quimiocinas e micropartículas circulantes em pacientes portadores da infecção crônica pelo VHC antes e durante a terapia tripla

Diante de constantes avanços no entendimento da infecção pelo VHC e mudanças no esquema terapêutico, torna-se necessário uma melhor compreensão da cinética de biomarcadores imunológicos ao longo do tratamento triplo e a sua importância na monitoração terapêutica e no alcance da resposta virológica sustentada (RVS) pelos pacientes ao término do tratamento. Neste estudo foi realizada uma caracterização cinética dos aspectos clínico-laboratoriais, perfil de quimiocinas e micropartículas circulantes em pacientes com infecção crônica pelo VHC, antes e durante a terapia tripla com interferon peguilado, ribavirina e inibidor de protease (telaprevir ou boceprevir). Foram avaliados 20 pacientes infectados com o vírus VHC com genótipo 1 em tratamento com terapia tripla e 20 indivíduos saudáveis, doadores de sangue, que compuseram o grupo controle para o estabelecimento dos valores de referência para análise de quimiocinas e micropartículas (MPs) circulantes. As quimiocinas CCL2/MCP-1, CCL5/RANTES, CXCL8/IL-8, CXCL9/MIG e CXCL10/IP10 e MPs derivadas de eritrócitos, células endoteliais, plaquetas, leucócitos e suas subpopulações foram quantificadas em soro e plasma, respectivamente,empregando citometria de fluxo,comparando os dados antes do tratamento (AT) e durante o tratamento (DT) nassemanas 2, 4, 8, 12, 24 e 48. Nossos resultados demonstraram que 70,0% dos pacientes eram do sexo masculino e 35,0% do sexo feminino, com idade média de 58,5 anos. Dos vinte pacientes avaliados 75,0% apresentavam o genótipo 1b e 30,0% o genótipo 1a do VHC. Quatorze pacientes completaram o tratamento triplo com 86,7% de RVS. Na análise de quimiocinas, houve um aumento de CCL2 na semana 12 em comparação com AT. CXCL8 aumentou na semana 12 em comparação com AT. CXCL9 e CXCL10 diminuíram na semana 24 em relação à semana 12 DT.

Na análise da frequência de MPs, aquelas originadas de neutrófilos diminuíram nas semanas 2 e 24, em comparação com a AT, diminuíram na semana 24 em comparação com a semana 8 DT e aumentaram na semana 8 em relação à semana 2 DT. As micropartículas derivadas de monócitos diminuíram nas semanas 2, 12 e 24 em comparação com AT e aumentaram na semana 48 em relação à semana 24. As MPs derivadas de linfócitos TCD3+diminuíram nas semanas 12, 24 e 48 em comparação com AT e nas semanas 24 e 48 em relação à semana 4 DT. Já aquelasoriginadas de linfócitos TCD4+ diminuíram nas semanas 12 e 24 em comparação com AT e diminuíram na semana 12 em comparação com a semana 4 DT.

Avaliações adicionais que utilizaram ferramentas de análise de sistemas biológicos revelaram que antes do tratamento houve uma elevação de enzimas hepáticas e frequências dasMPs nos pacientes, e a freqüência de altos produtores de quimiocinas foi baixa. Após o tratamento, houve uma diminuição progressiva das enzimas hepáticas e micropartículas, que foi acompanhado por aumento de quimiocinas com um pico na semana 12 do tratamento. Na semana 24 do tratamento, houve uma redução na maioria dos biomarcadores em comparação com a frequência mostrada antes do tratamento, exceto para CCL2 e CCL5 que ainda estavam sendo secretadas ao final do tratamento. Em suma, as análises do presente estudo mostraram que houve um declínio dos marcadores de agressão hepática, dos níveis de quimiocinas e da frequência de micropartículas no decorrer do tratamento, sugerindo, em síntese, que o tratamento e a redução ou eliminação do VHC promove um ambiente imunomodulador com retorno da resposta imunológica dentro dos padrões esperados na ausência da infecção viral. Para grande maioria dos pacientes que terminaram o tratamento, esse panorama está associado ao alcance de resposta virológica sustentada e, consequentemente, ao sucesso do tratamento triplo.

Needlestick accident resulting in occupational transmission of HCV: report of two cases

Occupational transmission of hepatitis C virus (HCV) through needlestick injury is a serious problem worldwide. Occupational transmission of HCV is estimated at an average rate between 0.5% and 0.75%. There are factors associated with increased risk of transmission, such as deep injuries, procedures involving hollow-bore needle placement in the source patient’s vein or artery, and high HCV RNA titer in the source patient. We describe two cases of HCV seroconversion in nursing assistants after different risk needlestick injuries...

Aspectos clínicos-laboratoriais, perfil de quimiocinas e micropartículas circulantes em pacientes portadores da infecção crônica pelo VHC antes e durante a terapia tripla / Clinical and laboratory aspects, Profile chemokines and circulating microparticles in patients with chronic HCV infection before and during triple therapy

Diante de constantes avanços no entendimento da infecção pelo VHC e mudanças no esquema terapêutico, torna-se necessário uma melhor compreensão da cinética de biomarcadores imunológicos ao longo do tratamento triplo e a sua importância na monitoração terapêutica e no alcance da resposta virológica sustentada (RVS) pelos pacientes ao término do tratamento. Neste estudo foi realizada uma caracterização cinética dos aspectos clínico-laboratoriais, perfil de quimiocinas e micropartículas circulantes em pacientes com infecção crônica pelo VHC, antes e durante a terapia tripla com interferon peguilado, ribavirina e inibidor de protease (telaprevir ou boceprevir). Foram avaliados 20 pacientes infectados com o vírus VHC com genótipo 1 em tratamento com terapia tripla e 20 indivíduos saudáveis, doadores de sangue, que compuseram o grupo controle para o estabelecimento dos valores de referência para análise de quimiocinas e micropartículas (MPs) circulantes. As quimiocinas CCL2/MCP-1, CCL5/RANTES, CXCL8/IL-8, CXCL9/MIG e CXCL10/IP10 e MPs derivadas de eritrócitos, células endoteliais, plaquetas, leucócitos e suas subpopulações foram quantificadas em soro e plasma, respectivamente,empregando citometria de fluxo,comparando os dados antes do tratamento (AT) e durante o tratamento (DT) nassemanas 2, 4, 8, 12, 24 e 48. Nossos resultados demonstraram que 70,0% dos pacientes eram do sexo masculino e 35,0% do sexo feminino, com idade média de 58,5 anos. Dos vinte pacientes avaliados 75,0% apresentavam o genótipo 1b e 30,0% o genótipo 1a do VHC. Quatorze pacientes completaram o tratamento triplo com 86,7% de RVS. Na análise de quimiocinas, houve um aumento de CCL2 na semana 12 em comparação com AT. CXCL8 aumentou na semana 12 em comparação com AT. CXCL9 e CXCL10 diminuíram na semana 24 em relação à semana 12 DT...