Implementación de una estrategia de revinculación a la atención en pacientes con infección crónica por el virus de la hepatitis C en el Hospital Central de las Fuerzas Armadas de Uruguay. Resultados preliminares

Resumen: Introducción: La infección crónica por el virus de la hepatitis C (VHC) es responsable de 400.000 muertes al año, asociadas fundamentalmente al desarrollo de cirrosis y carcinoma hepatocelular. El advenimiento de los nuevos antivirales de acción directa ha marcado un punto de inflexión en el tratamiento del VHC, llevando a casi 100% la curación de los pacientes tratados. En tal sentido, la OMS se ha fijado como objetivos para el año 2030, reducir un 90% las nuevas infecciones por el VHC y un 65% la mortalidad asociada a este virus, para lo cual es necesario el desarrollo de estrategias activas de diagnóstico y vinculación a la atención y tratamiento. El objetivo del trabajo es realizar un diagnóstico de situación de los pacientes infectados por el VHC en el Hospital Central de las Fuerzas Armadas (HCFFAA), e implementar y evaluar una estrategia secuencial de revinculación a la atención. Metodología: Se construyó la cascada de tratamiento mediante una estimación de los pacientes portadores de infección crónica por VHC basada en la prevalencia local y la revisión de historias clínicas de los pacientes asistidos en el servicio de Hepatología y Trasplante Hepático del HCFFAA. Se implementó una estrategia para contactar a los pacientes con infección por VHC de forma secuencial, buscando re-establecer el vínculo de estos con el servicio de salud, asegurando el acceso a la estadificación de la enfermedad hepática y al tratamiento antiviral. Resultados: La prevalencia global estimada de personas con infección crónica por VHC fue de 1.008 personas. De 135 pacientes con serología positiva, 113 tenían ARN confirmatorio, 76 habían recibido tratamiento y 70 habían alcanzado respuesta virológica sostenida. La implementación de la estrategia logró un aumento en la prescripción del tratamiento del 67% a 76% de los pacientes con infección crónica por VHC confirmada. Conclusiones: La implementación de la estrategia de revinculación fue exitosa, con un aumento de la prescripción del tratamiento antiviral en los pacientes candidatos a tratamiento. La búsqueda activa de los pacientes infectados no diagnosticados mediante el cribado es el siguiente paso para alcanzar los objetivos de erradicación.

Abstract: Introduction: Chronic infection by the hepatitis C virus (HCV) is responsible for 400,000 deaths per year, mainly associated with the development of cirrhosis and hepatocellular carcinoma. The advent of new direct-acting antivirals has marked a turning point in the treatment of HCV, leading to almost 100% cure of treated patients. In this sense, the WHO has set as objectives for the year 2030, to reduce new HCV infections by 90% and the mortality associated with this virus by 65%, for which it is necessary to develop active strategies for diagnosis and linkage to care and treatment. The objective of the work is to carry out a diagnosis of the situation of the patients infected by HCV in the Central Hospital of the Armed Forces (HCFFAA), and to implement and evaluate a sequential strategy of re-attachment to care. Methodology: The treatment cascade was constructed by estimating the number of patients with chronic HCV infection based on local prevalence and review of the medical records of patients seen in the Hepatology and Liver Transplant service of the HCFFAA. A strategy was implemented to contact patients with HCV infection sequentially, seeking to re-establish their link with the health service, ensuring access to liver disease staging and antiviral treatment. Results: The estimated global prevalence of people with chronic HCV infection was 1,008 people. Of 135 patients with positive serology, 113 had confirmatory RNA, 76 had received treatment, and 70 had achieved sustained virologic response. The implementation of the strategy achieved an increase in the prescription of treatment from 67% to 76% of patients with confirmed chronic HCV infection. Conclusions: The implementation of the rebinding strategy was successful, with an increase in the prescription of antiviral treatment in patients who are candidates for treatment. Active search for undiagnosed infected patients through screening is the next step to achieve eradication goals.

Resumo: Introdução: A infecção crônica pelo vírus da hepatite C (HCV) é responsável por 400.000 óbitos por ano, principalmente associada ao desenvolvimento de cirrose e carcinoma hepatocelular. O advento de novos antivirais de ação direta marcou um ponto de virada no tratamento do HCV, levando à cura de quase 100% dos pacientes tratados. Nesse sentido, a OMS estabeleceu como objetivos para o ano de 2030, reduzir em 90% as novas infecções por HCV e a mortalidade associada a este vírus em 65%, para o que é necessário desenvolver estratégias ativas de diagnóstico e vinculação aos cuidados e tratamento. O objetivo do trabalho é realizar um diagnóstico da situação dos pacientes infectados pelo HCV no Hospital Central das Forças Armadas (HCFFAA), e implementar e avaliar uma estratégia sequencial de reinserção aos cuidados. Metodologia: A cascata de tratamento foi construída estimando o número de pacientes com infecção crônica pelo HCV com base na prevalência local e revisão dos prontuários dos pacientes atendidos no serviço de Hepatologia e Transplante de Fígado do HCFFAA. Foi implantada uma estratégia de contato sequencial dos pacientes com infecção pelo HCV, buscando restabelecer o vínculo com o serviço de saúde, garantindo o acesso ao estadiamento da doença hepática e ao tratamento antiviral. Resultados: A prevalência global estimada de pessoas com infecção crônica pelo HCV foi de 1.008 pessoas. Dos 135 pacientes com sorologia positiva, 113 tiveram RNA confirmatório, 76 receberam tratamento e 70 alcançaram resposta virológica sustentada. A implementação da estratégia conseguiu um aumento na prescrição de tratamento de 67% para 76% dos pacientes com infecção crônica pelo HCV confirmada. Conclusões: A implementação da estratégia de religação foi bem sucedida, com aumento da prescrição do tratamento antiviral em pacientes candidatos ao tratamento. A busca ativa de pacientes infectados não diagnosticados por meio de triagem é o próximo passo para atingir as metas de erradicação.

Hepatitis C: clinical and biological features related to different forms of cocaine use / Hepatite C: características clínicas e biológicas relacionadas às diferentes formas de uso da cocaína

Abstract Introduction Hepatitis C virus (HCV) infection is related with several liver diseases such as cirrhosis and hepatocellular carcinomas, leading to more than 0.5 million deaths every year and to a great global burden. It is known that injection drug users show a high prevalence of HCV infection, being considered a risk group for this disease. Cocaine users seem to be in greater risk than other drug users, and several hypotheses for this association are being studied. Aim To review data on HCV infection in cocaine users, taking into consideration the relevance of the different routes of drug administration and other risk behaviors. Methods This was a narrative review performed in the main scientific databases. Results and conclusion Data suggest that cocaine use could be associated with HCV infection due to the specificities of cocaine consumption pattern, even in those subjects who do not inject drugs, in addition to other risky behaviors, such as tattooing and unprotected sex. Injectable cocaine users seem to be more susceptible to contamination than users who do not inject drugs. However, evidence is pointing to the possibility of infection by sharing drug paraphernalia other than syringes. Moreover, specific immune system impairments caused by cocaine use are also being linked with HCV infection susceptibility, persistence and increased pathological effects.

Resumo Introdução O vírus da hepatite C (HCV) está relacionado com graves patologias hepáticas, como a cirrose e o carcinoma hepatocelular, causando mais de meio milhão de mortes todos os anos, o que reflete um problema de saúde mundial. Sabe-se que usuários de drogas injetáveis possuem alta prevalência de infecção pelo HCV, sendo por isso considerados um dos maiores grupos de risco. Usuários de cocaína parecem ter maior risco de contrair o vírus do que usuários de outras drogas, e diversas hipóteses para essa associação estão sendo estudadas. Objetivo Revisar evidências de associação da infecção pelo HCV em usuários de cocaína, considerando a relevância das diferentes formas de administração da droga e comportamentos de risco. Métodos Esta foi uma revisão narrativa realizada nos principais bancos de dados científicos. Resultados e conclusão As evidências atuais sugerem que o uso de cocaína pode estar associado com a infecção por HCV devido às especificidades do padrão de consumo da droga, mesmo naqueles indivíduos que não fazem uso de drogas injetáveis, além de outros comportamentos de risco, como tatuagens e sexo desprotegido. Usuários de cocaína injetável parecem estar mais suscetíveis à contaminação do que usuários de cocaína não injetável. Entretanto, há a possibilidade de infecção devido ao compartilhamento de outros equipamentos de uso além das seringas (cachimbos, por exemplo). Além disso, prejuízos do sistema imune causados pela cocaína também parecem estar associados com a suscetibilidade de infecção pelo HCV, além da manutenção e piora dos sintomas da doença.

Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

ABSTRACT HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

Effect of hepatitis C virus infection on the expressions of multiple sialyltransferases and galactosyltransferases in Huh7.5.1 cell / 中国生化药物杂志

Objective To investigate the altered glycotransferases and glycan profile in HCV-infected cells, the expression levels of 35 kinds of sialyltransferases and galactosyltransferases were evaluated in hepatitis C virus (HCV) infected Huh7.5.1 cell cultured model.Methods Western blot was used to measure the expressions of HCV-nonstructural protein NS3 and and quantitative real-time PCR (qRT-PCR) was performed to determine HCV-RNA levels and mRNA levels of 35 kinds of sialyltransferases and galactosyltransferases.Lectin microarray was used to compare the glycan profiles of sialyltransferases-and galactosyltransferases-associated glycan-profile in Huh7.5.1 cells and HCV infected Huh7.5.1 cells.Results Among the 35 kinds of sialyltransferases and galactosyltransferases, the mRNA levels of four sialyltransferases (including ST3Gal Ⅲ, ST6GalNAC Ⅲ, ST8Sia Ⅲ and ST8SiaⅣ) and five galactosyltransferases (including B3GALT1, B3GALT 2, B3GALT3, B3GALT4 and B4GALNT2) were found to be 11-45 fold higher in HCV-infected cells compared with naive Huh7.5.1 cells.The up-regulated level of B3GALT 1 was the most evident (45-fold change), followed by ST8Sia Ⅳ and ST8Sia Ⅲ, with 39-and 37-fold respectively.Consistently, lectin microarray showed that glycans recognized by EBL (binding terminal sialic acid, Neu5Acα6Gal, 1.97-fold change), ECA letin (binding terminal galactose, Galβ1,4GalNAc,4.3-fold change), and ACA(binding terminal galactose, Galβ1-3GalNAc, 3-fold change) were elevated in glycoprotein products of sialyltransferase and galactosyltransferase respectively.Conclusion HCV infection causes the increased expression levels of mutiple sialyltransferases and galactosyltransferases in Huh7.5.1 cell line and hence the upregulation of glycan profiles of the glycoproteins.These results provide potential therapeutic targets and diagnostic markers for HCV infection and insights on the molecular mechanism of HCV infection.

Hcv infection trrough perforating and cutting mterial among candidates for bloood donation in belém, Brazilian amazon / Infecção pelo HCV através de materiais cortantes e perfurantes entre candidatos à doação de sangue em Belém, Amazônia Brasileira

This study evaluated epidemiological factors for HCV infection associated with sharing perforating and cutting instruments among candidates for blood donation (CBD) in the city of Belém, Pará, Brazilian Amazon. Two definitions of HCV infection cases were used: anti-HCV positivity shown by EIA, and HCV-RNA detection by PCR. Infected and uninfected CBD completed a questionnaire about possible risk factors associated with sharing perforating and cutting instruments. The information was evaluated using simple and multiple logistic regressions. Between May and November 2010, 146 (1.1%) persons with anti-HCV antibodies and 106 (0.8%) with HCV-RNA were detected among 13,772 CBD in Belém. Risk factors associated with HCV infection based on the EIA (model 1) and PCR (model 2) results were: use of needles and syringes sterilized at home; shared use of razors at home, sharing of disposable razors in barbershops, beauty salons etc.; and sharing manicure and pedicure material. The models of HCV infection associated with sharing perforating and cutting instruments should be taken into account by local and regional health authorities and by those of other countries with similar cultural practices, in order to provide useful information to guide political and public strategies to control HCV transmission.

Este estudo avaliou fatores epidemiológicos para infecção pelo HCV associados ao compartilhamento de instrumentos cortantes e perfurantes em candidatos à doação de sangue (CDS) na cidade de Belém, Pará, Amazônia Brasileira. Duas definições de infecção pelo HCV foram utilizadas: positividade por anti-HCV detectada por EIA, e HCV-RNA detectado por PCR. CDS infectados e não-infectados preencheram questionário sobre possíveis fatores de risco associados com o compartilhamento de instrumentos cortantes e perfurantes. As informações foram avaliadas usando regressão logística simples e múltipla. Entre maio e novembro de 2010, 146 (1,1%) indivíduos com anticorpos anti-HCV e 106 (0,8%) com HCV-RNA foram detectadas entre 13.772 CDS em Belém. Os fatores de risco associados à infecção pelo HCV baseado em resultados de EIA (modelo 1) e PCR (modelo 2) foram: uso de agulhas e seringas esterilizadas em casa, uso compartilhado de lâminas em casa, compartilhamento de lâminas em barbearias, salões de beleza, etc., e compartilhamento de material de manicure e pedicure. Os modelos de infecção pelo HCV associados com o compartilhamento de instrumentos cortantes e perfurantes devem ser considerados pelas autoridades de saúde local e regional e de países com práticas culturais semelhantes, a fim de fornecer informações uteis para direcionar estratégias e políticas públicas de controle da transmissão do HCV.

Success of antiviral therapy in chronic hepatitis C infection relates to functional status of myeloid dendritic cells.

Chronic hepatitis C infection poses a major global health predicament and appears to be potent threat to mankind. The treatment in wide use is interferon/ribavirin combination therapy which is generally effective in about 60-70 per cent of patients carrying genotype 3 and causes significant morbidity. The response to therapy is largely guided by limited number of factors such as genotype of virus, rapid virological response, ethnicity, pre-therapy viral load, etc. While involvement of host genetic factors has been a major focus of research in playing an important role in the outcome of disease, the role of immune system cannot be marginalized. Poor cellular trafficking and suboptimal T cell responses in liver, the hall marks of chronic hepatitis C virus infection, might be attributed to defective antigen presentation. Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease. Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy. In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

Effects of chronic HCV infection and spontaneously resolved HCV infection on serum trace elements and their relationships with serum albumin and circulating HCV RNA load / 中华微生物学和免疫学杂志

Objective To comparatively analyze serum levels of zinc , iron, magnesium, calcium, copper and phosphorus and their relationships with serum albumin and circulating HCV viral load in patients with chronic HCV infection , subjects with spontaneously resolved HCV infection and healthy subjects . Methods Serum levels of the six trace elements in patients with chronic HCV infection (n=59), subjects with spontaneously resolved HCV infection (n=65) and healthy subjects (n=48) were measured by a flame atomic absorption spectrophotometer and then a comparative analysis was performed to analyze the differences among the three groups .The relationships of the six trace elements with serum albumin and HCV viral load were analyzed among patients with chronic HCV infection .Results Compared with healthy subjects , the levels of serum zinc were significantly decreased , but serum levels of iron , copper , phosphorus were signifi-cantly increased in patients with chronic HCV infection .There was a significant positive correlation between the levels of zinc(r=0.4022, P=0.0016)and albumin in patients with chronic HCV infection with ALT no less than 40 IU/L, whereas negative correlations were presented between trace elements of iron ( r=-0.3001, P=0.0209), copper (r=-0.3856, P=0.0036), phosphorus (r=-0.3600, P=0.0075) and serum albumin.The circulating HCV viral load was negatively correlated with serum zinc (r=-0.4367, P=0.0005), but positively correlated with serum copper (r=0.3328, P=0.0139).The serum levels of six trace elements showed no significant differences between healthy subjects and spontaneous resolvers of HCV infection.Moreover, no significant differences of serum calcium and magnesium were found among the three groups.Conclusion Chronic HCV infection can induce abnormal serum levels of zinc , iron, copper and phosphorus and the abnormal serum levels of trace elements were closely related with liver function and HCV viral load.With the spontaneous clearance of HCV infection , the serum levels of trace elements could restore to normal .

Risk factors for hepatitis C disease in Tando Allahyar, Pakistan: a case-control study.

Objective: Present study was undertaken to explore the epidemiological and dietary risk factors for hepatitis C disease in Tando Allahyar during June to December 2007. Materials and methods: 140 Hepatitis C patients and 149 controls (age, sex and locality matched with no personal or family history of hepatitis C) were randomly selected from the Tando Allahyar population during June 2007 to December 2007. A standard questionnaire specially developed for that purpose, was distributed among patients and controls. Accurate rapid card test was performed to confirm Hepatitis C virus (HCV) positive or negative patients and controls. O.R with 95% confidence interval was computed and p values were calculated by chi square test. Results: Over all findings showed that among 140 HCV patients 64% were females and 36% males (mean age range was 20-48 years). Our results showed strong positive association of sedentary life style (OR=4, 95% CI, 1.48-10.6, p=0.005), marital status, +ve family history, B+ve blood group, piercing, syringe use (70%), multiple pregnancies (OR=4.72, 95% CI, 1.47-15.15, p=0.008), blood transfusion (OR=4.4, 95% CI, 1.2-14.95, p=0.017), take out food debris by office pins (NS), shave at barber’s shop (NS), dental procedures (NS), medicines used in past (OR=3.08, 95% CI, 1.2-7.71, P=0.016), G.I.T diseases (OR =8.66, 95% CI, 1.28-55.58, p=0.023), stones of kidney or gallbladder, jaundice, Tuberculosis and psychological problems (OR =2.5, 95% CI, 1.04-6.13, P=0.04) with hepatitis C disease. We did not find any association of surgery, BMI, ENT, diseases, meat consumption and smoking with the disease. Vegetables OR =0.842, 95% CI, 0.361-1.964, P=0.694), pulses, tomatoes (OR =0.31, 95% CI, 0.041-2.53, P=0.31), and tea (OR =0.598, 95% CI, 0.251-1.431, P=0.25) were found to be the protective factors for Hepatitis C disease. Conclusion: Sedentary life style, multiple pregnancies, blood transfusion, medicines used in past, G.I.T diseases, and psychological problems are significantly positively associated with Hepatitis C disease.

Severe form of psoriasis occurring after peginterferon plus ribavirin treatment, and frequent resort to filgrastim rescue, in a woman treated for a chronic HCV infection

Associated treatment with pegylated interferon plus specific antiviral compounds significantly improved the prognosis of chronic hepatitis C and B, although antiviral drugs (especially interferon and its derivatives) tend to be myelotoxic and also some rescue treatments, like human recombinant granulocyte colony-stimulating factors (which are extensively administered in order to correct neutropenia induced by antiviral therapy), may alsobe involved in prompting or exacerbating cutaneous psoriasis and its systemic complications. A representative case report of a woman with a chronic, progressive, hepatitis C, who underwent long-term treatment with combined pegylated interferon plus ribavirin, and resorted to multiple cycles of filgrastim to recover a severe, recurring granuloytopenia caused by antiviral therapy itself, and to maintain an effective dosage of anti-HCV antivirals, developed an extensive and severe cutaneous psoriasis, which improved only after specific cyclosporin treatment. From a pathogenetic point of view, in our case it remains extremely difficult to distinguish the role of pegylated interferon from that of the accompanying ribavirin, from that of the frequently administered granulocyte growth factor (filgrastim), since all mentioned drugs were administered concurrently during many months, and according to the existing literature evidences, all of them have a potential to induce psoriasis as a potential untoward effect in subjects suffering from chronic hepatitis. Cyclosporin treatment obtained a stable remission of this last severe cutaneous complication, but the efforts to contain the progression of the underlying evolutive hepatitis C were blunted by the difficult-to-treat genotype 1 HCV infection, and the frequent need to lower drug dosages and/or to interrupt antiviral therapy, because of myelotoxic and later cutaneous complications prompted by anti-HCV therapy itself

Transverse myelitis associated to HCV infection

Complications involving the central nervous system in patients suffering from hepatitis C virus (HCV) infectionhave been rare. Among them, it appears the transverse myelitis, which has already been reported in likely association with HCV. This paper presents the case study of a 65-year-old woman who developed cervical transverse myelitis linked to chronic HCV infection and anti-HCV antibodies in the spinal fluid, being excluded other etiologies for transverse myelitis. Current evidence has reinforced the likely association between chronic HCV infection and transverse myelitis, especially as recurrent manifestations of the disease. These findings reveal the need for more searching to establish the causal relationship between transverse myelitis and hepatitis C.

Factors Predictive of Response to Interferon Therapy in Chronic HCV Infection / 대한간학회지

BACKGROUND/AIMS: Although interferon-a(IFNa) is currently the most effective antiviral agent for treating patients with chronic hepatitis C, its efficacy is not always reliable. Factors suggested to infruence outcome of IFN-a therapy for chronic hepatitis C are histological activity, level of viremia and HCV genotype, etc. The aim of this study was to determine the relationship between several pretreatment factors and response to IFN-a therapy in patients with chronic HCV infection. METHODS: Fifty-four patients with chronic HCV infection(47 with chronic hepatitis and 7 with liver cirrhosis) who received IFN-a(2a or 2b) therapy(3 6 MU, three times a week, for 3 12 months) were included. Level of serum HCV RNA(50 patients), HCV genotype(27 patients) and IgM anti- HCV(21 patients) during pretreatment period were assayed. RESULTS: Overall, 19(35%) subjects achieved sustained response(SR), 12(22%) had transient response(TR) and 23(43%) did not respond (nonresponse;NR). Mean age of patients with SR, TR and NR was 46+ 10, 51+ 7.5 and 54+ 9.7 years, respectively(p<0.05 between SR and NR). Among 30 patients with biopsy-proven chronic hepatitis, 13(43%) achieved SR;but only one(14%) in 7 patients with liver cirrhosis. Mean serum HCV RNA level(X10' copies/ml) was higher in nonresponders(7,7+ 13.0) compared with SR(2.3+ 2. 7) or TR(3.1+ 4.9), although statistically insignificant HCV genotyping in 27 patients revealed type la in 5(18.5%), 1b in 14(52%), 2a in 5(18.5%), 2b in 1(3.7%) and 4 in 2(7%), respectively. In non-1b patients, SR rate was significantly higher than 1b patients(69.2% vs. 21.4%, p=0.03). Although IgM anti-HCV was positive in 12(57%) among 21 patients studied, the positive rate and the titer of IgM anti-HCV was not significantly different in three groups. CONCLUSION: Our results suggest that in patients with chronic hepatitis C, infection with genotype 1b, old age, high serum HCV RNA level and the presence of cirrhosis would predict poor response to IFN therapy.