Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

Hepatitis E seroprevalence and associated risk factors in Croatian liver transplant recipients

Abstract INTRODUCTION Solid-organ transplant recipients are at risk of hepatitis E virus (HEV) infection. We analyzed the seroprevalence/risk factors of HEV in Croatian liver transplant recipients. METHODS Two hundred forty-two serum samples were tested for HEV immunoglobuline IgG/IgM and HEV RNA. Sociodemographic data and risk factors were collected using a questionnaire. RESULTS HEV IgG seroprevalence rate was 24.4%. Positive/equivocal HEV IgM were found in two patients. HEV RNA was not detected. Logistic regression showed that older age, female gender, rural area/farm, water well, and septic tank were associated with HEV seropositivity. CONCLUSIONS This study revealed a high exposure rate to HEV in Croatian liver recipients.

South-South Cooperation: Brazilian experiences in South America and Africa / Cooperação Sul-Sul: experiências brasileiras na América do Sul e na África

Over recent years Brazil has played an increasingly active role internationally, the result of its model of integration and its foreign policy directives. The health sector is a valuable and strategic area for Brazilian technical cooperation to achieve various objectives, including its development goals. This article describes the main directives of Brazilian foreign policy, conceptually defining and characterizing South-South Cooperation, illustrated through an analysis of two Brazilian technical cooperation initiatives in healthcare: one in South America, the other in Africa. The study concludes that, irrespective of the interests and power asymmetries existing in South-South Cooperation, the objectives of this cooperation were achieved through the technical work.

Nos últimos anos, o Brasil foi ativo no âmbito internacional, tanto por seu modelo de inserção como pelas diretrizes de política externa. O setor saúde é uma ferramenta valiosa e estratégica utilizada pela cooperação técnica brasileira para lograr seus objetivos de desenvolvimento. Este artigo descreve as principais diretrizes de política externa brasileira, conceitua e caracteriza a Cooperação Sul-Sul, ilustrada mediante análise de duas iniciativas de cooperação técnica em saúde do Brasil: na América do Sul e na África. O estudo conclui que, independentemente dos interesses e das assimetrias de poder que existem na Cooperação Sul-Sul, os objetivos dessa cooperação foram alcançados por meio do trabalho técnico.

Social and immunological differences among uninfected Brazilians exposed or unexposed to human immunodeficiency virus-infected partners

Understanding the social conditions and immunological characteristics that allow some human immunodeficiency virus (HIV)-exposed patients to remain uninfected represents an on-going challenge. In this study, the socio-demographic and sexual behaviour characteristics and immune activation profiles of uninfected individuals exposed to HIV-infected partners were investigated. A confidential and detailed questionnaire was administered and venous blood was tested using HIV-1/enzyme immunoassays, plasma HIV-1 RNA levels/bDNA and immunophenotyping/flow cytometry to determine the frequencies of CD4 and CD8 T cells expressing activation markers. The data analysis showed significant differences (p < 0.05) for immune parameters in individuals who were uninfected, albeit exposed to HIV-infected partners, compared with unexposed individuals. In particular, the exposed, uninfected individuals had a higher frequency (median, minimum-maximum) of CD4+HLA-DR+ (4.2, 1.8-6.1), CD8+HLA-DR+ (4.6, 0.9-13.7), CD4+CD45RO+ (27.5, 14.2-46.6), CD4+CD45RO+CD62L+ (46.7, 33.9-67.1), CD8+CD45RA+HLA-DR+ (12.1, 3.4-35.8) and CD8+CD45RO+HLA-DR+ (9.0, 3.2-14.8) cells, a decreased percentage of CD8+CD28+ cells (11.7, 4.5-24.0) and a lower cell-surface expression of Fcγ-R/CD16 on monocytes (56.5, 22.0-130.0). The plasma HIV-1 RNA levels demonstrated detectable RNA virus loads in 57% of the HIV-1+ female partners. These findings demonstrate an activation profile in both CD4 and CD8 peripheral T cells from HIV-1 exposed seronegative individuals of serodiscordant couples from a referral centre in Belo Horizonte, state of Minas Gerais.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

Hepatitis B and C virus infection among Brazilian Amazon riparians / Infecção pelo virus da hepatite B e C em ribeirinhos da Amazônia brasileira

INTRODUCTION: Viral hepatitis is a major public health concern in Brazil. There are few past studies on this issue, especially among riparian communities. This study aims at determining the seroprevalence of viral hepatitis B and C in the riparian community of Pacuí Island, within the Cametá municipality of Pará State, Brazil. Moreover, this study aims to investigate the principal risk factors that this community is exposed to. METHODS: The current study has accessed blood samples from 181 volunteers who have answered an epidemiological questionnaire. Analyses on serological markers have been tested with commercial ELISA kits for detecting HBsAg, total anti-HBc, anti-HBs, and anti-HCV. Within seroreactive patients for HCV, RT-PCR and line probe assay have been performed to identify the viral genotype. RESULTS: In the serological marker analysis for hepatitis B, no reactivity for HBsAg, rate of 1.1 percent for total anti-HBc, and rate of 19.3 percent for anti-HBs have been observed. On hepatitis C, 8.8 percent seroprevalence has been found, in which 62.5 percent have gotten viral RNA. Among the risk factors studied, the following have been highlighted: non-use of condoms, sharing of cutting instruments, use of illicit drugs, and reports of family disease with HBV or HCV. CONCLUSIONS: The vaccination coverage against HBV is low, and the high prevalence of HCV within this community has been observed.

INTRODUÇÃO: As hepatites virais constituem um importante problema de saúde pública no mundo. No Brasil existem poucos estudos sobre esta questão, especialmente entre as comunidades ribeirinhas. O objetivo deste estudo foi determinar a soroprevalência das hepatites B e C virais na comunidade ribeirinha da Ilha do Pacuí, no Estado do Pará, Brasil, e investigar os principais fatores de risco principal a que está comunidade está exposta. MÉTODOS: O presente estudo avaliou amostras de sangue de 181 voluntários que responderam a um questionário epidemiológico. Análises de marcadores sorológicos foram testados com kits comerciais de ELISA para detecção de HBsAg, anti-HBc total, anti-HBs e anti-VHC. Nos pacientes reagentes para VHC, RT-PCR e um line probe assay foi realizado para identificar o genótipo viral. RESULTADOS: Na análise dos marcadores sorológicos para hepatite B, observou-se taxas de 1,1 por cento para anti-HBc total e 19,3 por cento para anti-HBs, o marcador sorológico HBsAg não foi encontrado nesta população. Para a hepatite C foi encontrada um soroprevalência de 8,8 por cento, destes 62,5 por cento tinham RNA viral. Entre os fatores de risco estudados se destacaram: a não-utilização de preservativos, o compartilhamento de instrumentos cortantes, uso de drogas ilícitas e relatos de doença na família com VHB ou VHC. CONCLUSÕES: Observamos que a cobertura de vacinação contra o VHB é baixa e uma alta prevalência da hepatite C nesta comunidade.

Analysis of the sustained virological response in patients with chronic hepatitis C and liver steatosis / Análise da resposta virológica sustentada em pacientes com hepatite crônica pelo vírus da hepatite C e esteatose hepática

CONTEXT: Chronic hepatitis C as well as non-alcoholic fatty liver disease are recognized as the main cause of liver disease in Western countries. It is common to see the concomitance of the diseases and the influence of steatosis in the sustained virological response of patients with hepatitis C virus. OBJECTIVE: Assess the sustained virological response in chronic hepatitis C patients according to the presence of liver steatosis. METHODS: One hundred sixty patients with chronic hepatitis C were retrospectively evaluated. Demographic data such as gender, age, body mass index, presence of diabetes mellitus and systemic arterial hypertension, virus genotype and use of pegylated interferon were analyzed, as was the staging of fibrosis and the presence of steatosis at histology. RESULTS: Most patients were male (57.5 percent), with a mean age of 48 ± 9.7 years. The most frequent genotype observed was 3 (56.9 percent) and, in the histological evaluation, steatosis was observed in 65 percent of the patients (104/160). Sustained virological response in patients with steatosis occurred in 38.5 percent, and in 32.1 percent in patients without steatosis (P = 0.54). When we analyzed possible factors associated with the presence of steatosis, only body mass index and systemic arterial hypertension revealed a significant association. When the factors that influenced sustained virological response were evaluated in a logistic regression, genotype and use of pegylated interferon proved to be independent factors associated to the response. CONCLUSION: In the evaluated patients the presence of liver steatosis did not influence the sustained virological response of patients with chronic hepatitis C treated with interferon and ribavirin.

CONTEXTO: Tanto a hepatite crônica pelo vírus C quanto a doença hepática gordurosa não-alcoólica são reconhecidas como causas frequentes de doença hepática nos países ocidentais. É comum observar a concomitância das duas doenças e a influência da esteatose na resposta virológica sustentada dos pacientes com hepatite crônica pelo vírus C. OBJETIVO: Avaliar a resposta virológica sustentada nos pacientes com hepatite crônica pelo vírus C de acordo com a presença de esteatose. MÉTODOS: Foram avaliados, retrospectivamente, 160 pacientes com hepatite crônica C. Dados demográficos, como sexo, idade, índice de massa corpórea, presença de diabetes mellitus e hipertensão arterial sistêmica, genótipo do vírus e uso de interferon peguilado foram analisados, bem como o estadiamento e a presença de esteatose, quando da histologia. RESULTADOS: A maioria dos pacientes era masculina (57,5 por cento), com média de idade de 48 anos ± 9,7. O genótipo mais frequente foi o 3 (56,9 por cento) e, na avaliação histológica, foi observada esteatose em 65 por cento dos pacientes (104/160). A resposta virológica sustentada nos pacientes com esteatose foi de 38,5 por cento, sendo de 32,1 por cento nos pacientes sem esteatose (P = 0,54). Quando se analisaram possíveis fatores associados à presença de esteatose, somente índice de massa corpórea e hipertensão arterial sistêmica estiveram associados de forma significativa. Quando se avaliaram em regressão logística os fatores que influenciaram a resposta virológica sustentada, genótipo e uso de interferon peguilado mostraram-se fatores independentes associados à resposta. CONCLUSÃO: A presença de esteatose hepática não influenciou a resposta virológica sustentada de pacientes com hepatite crônica pelo vírus C tratados com interferon e ribavirina.

Soluble inflammatory markers as predictors of virological response in patients with chronic hepatitis C virus infection treated with interferon-α plus ribavirin

The host immune response plays an important role in viral clearance in patients who are chronically infected with hepatitis C virus (HCV) and are treated with interferon and ribavirin. Activation of the immune system involves the release of pro and anti-inflammatory molecules that can be measured in plasma samples. The present study aimed to evaluate the association between pretreatment plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNF-R) and the virological response in treated patients with chronic hepatitis C infection. Forty-one chronically-infected HCV patients that were being treated with interferon-α (IFN-α) plus ribavirin were included in the study. Socio-demographic, clinical and laboratory data were collected and pretreatment plasma levels of chemokine CCL2, CCL3, CCL11, CCL24, chemokine CXCL9, CXCL10, sTNF-R1 and sTNF-R2 were measured. The virological response was assessed at treatment week 12, at the end of treatment and 24 weeks after treatment. Pretreatment CXCL10 levels were significantly higher in patients without an early virological response (EVR) or sustained virological response (SVR) compared to responders [512.9 pg/mL vs. 179.1 pg/mL (p = 0.011) and 289.9 pg/mL vs. 142.7 pg/mL (p = 0.045), respectively]. The accuracy of CXCL10 as a predictor of the absence of EVR and SVR was 0.79 [confidence interval (CI) 95 percent: 0.59-0.99] and 0.69 (CI 95 percent: 0.51-0.87), respectively. Pretreatment plasma levels of the other soluble inflammatory markers evaluated were not associated with a treatment response. Pretreatment CXCL10 levels were predictive of both EVR and SVR to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy.

Hepatitis C seroprevalence and correlation between viral load and viral genotype among primary care clients in Mexico

OBJECTIVE: To measure hepatitis C virus (HCV) sero-prevalence, prevalence, hepatitis risk characteristics frequency, and genotype correlation with viral load among clients attending health care clinics. MATERIAL AND METHODS: Venous blood samples from l12 226 consecutive consenting adults were collected from January 2006 through December 2009. HCV antibodies were detected by immunoassay. HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA test. RESULTS: The HCV seroprevalence observed was l.5 percent (C.I. 95 percent l.3-l.7), from seropositive individuals 60.9 percent reported previous blood transfusion, 28.3 percent declared to have relatives with cirrhosis, 25.2 percent had tattoos or piercings, and 6.9 percent referred to have used drugs. Male gender and transfusion (p<0.00l) were the most frequent hepatitis risk characteristics in the HCV seropositive group. Among seropositive subjects 48.3 percent presented HCV RNA.The most frequent genotype detected in all geographic areas of Mexico was l (subtype lA, 33 percent; subtype lB, 21.4 percent) followed by genotype 2 (subtype 2A, 8.50 percent). Subjects with genotype 1 had a significant correlation with the highest viral load. CONCLUSIONS: Our results show that nearly half of seropositive individuals are chronically infected. HCV infection has been shown in this study to be an emerging health problem in Mexico.

OBJETIVO: Medir la seroprevalencia y prevalencia del virus de hepatitis C (VHC), la frecuencia de caracteristicas de riesgo y la correlacion genotipica con la carga viral en sujetos asistentes a clinicas de medicina familiar. MATERIAL Y METODOS: muestras de sangre venosa se colectaron de l12 226 adultos, previo consentimiento informado, de enero 2006 hasta diciembre 2009, para la deteccion de anticuerpos contra VHC por ELISA. La deteccion de RNA-VHC y el genotipo viral se realizo mediante qRT-PCR. RESULTADOS: La seroprevalencia de VHC fue l.5 por ciento (C.I. 95 por ciento l.3-l.7), 60.9 por ciento reportaron transfusion sanguinea previa, 28.3 por ciento dijo tener familiares cercanos con cirrosis, 25.2 por ciento tenian tatuajes o piercing y 6.9 por ciento refirio ser usuario de drogas intravenosas. El ser hombre, el antecedente de transfusiones y el uso de drogas (p<0.00l), fueron los factores con mayor frecuencia en el grupo VHC seropositivo. La prevalencia del RNA-VHC en seropositivos fue de 48.3 por ciento. El genotipo mas frecuente en todas las areas geograficas de Mexico fue el l (subtipo lA, 33 por ciento; subtipo lB, 21.4 por ciento) seguido por el genotipo 2 (subtipo 2A, 8.50 por ciento). Se observó una correlación positiva de 51 por ciento con la carga viral más alta y el genotipo viral 1A. CONCLUSIONES: Nuestros resultados muestran que cerca de la mitad de individuos seropositivos están infectados crónicamente. Esta infección debe considerarse como un problema emergente de salud pública en México.

Resposta virológica sustentada em pacientes com co-infecção pelos genótipos 1 e 2 do vírus da hepatite C, com apenas nove semanas de terapêutica antiviral: relato de caso / Sustained virological response in patients with coinfection by hepatitis C virus genotypes 1 and 2, after just nine weeks of antiviral therapy: case report

Relata-se um paciente do sexo masculino com 67 anos e sorologia positiva para o vírus da hepatite C (HCV). Exames moleculares revelaram a presença do RNA do HCV, com carga viral de 2.000 cópias/mL e genótipos 1 e 2. O tratamento foi com alfapeginterferon-2a, 180mcg/semana e ribavirina, 1.000mg/dia. Na quarta semana de tratamento, a carga viral para o HCV era indetectável. Na nona semana, o paciente apresentou hematêmese, piora do quadro de astenia, inapetência e comprometimento do estado geral, quando o tratamento foi descontinuado. O PCR foi negativo após 6 meses e permaneceu assim após um ano. O paciente encontra-se assintomático.

A report of a 67 year-old male patient with positive serology for HCV. PCR revealed the presence of HCV RNA, viral load of 2,000 copies/mL and genotypes 1 and 2. The pacient was treated with peginterferon alfa-2a at 180mcg/week and ribavirin at 1,000mg/day. In week four of treatment, HCV viral load was undetectable. In week nine, the patient developed hematemesis, worsening of asthenia, anorexia and impaired general condition, so the treatment was discontinued. The PCR was negative six months and one year after the cessation of treatment. The patient remains asymptomatic.

Long-term follow-up of patients with chronic hepatitis C with sustained virologic response to interferon

BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73 percent) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1 percent of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0 percent) received one treatment course, 29 (16.7 percent) received two courses, and 11 (6.3 percent) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2 percent), genotype 3 (40.8 percent) and genotype 2 (10.3 percent). Genotype was undetermined in 8.7 percent of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.

Hepatitis C in hemodialysis: the contribution of injection drug use

BACKGROUND: Hepatitis C virus (HCV) infection is the most common cause of acute or chronic hepatitis in patients on hemodialysis (HD). The purpose of this study was to describe the prevalence of positive HCV RNA and investigate injection drug use as an emerging risk factor in patients with chronic renal disease on HD. METHODS: This was a multicenter cross-sectional study with 325 patients with chronic renal disease on HD in the period between August 1, 2005 to August 30, 2006, receiving care at four institutions in the city of Porto Alegre, Southern Brazil. Epidemiological data were collected by means of a structured questionnaire. The following laboratory tests were performed: alanine aminotransferase (ALT), anti-hepatitis C virus antibodies (anti-HCV), and qualitative polymerase chain reaction (PCR). RESULTS: Of 325 patients, 68 had positive HCV RNA results. The comparison between patients with positive and negative PCR results revealed significant differences in duration of HD (mean = 71 versus 52.4 months; p = 0.02); previous blood transfusion (92 percent versus 72 percent; p < 0.01); injection drug use (13 percent versus 0.7 percent; p < 0.01); anti-HCV positivity at start of HD therapy (60 percent versus 4 percent; p < 0.01); and mean ALT value (39 versus 26.5; p < 0.01). Logistic regression analysis showed a positive HCV RNA independently associated to being on HD for more than five years [OR: 2.1 (95 percent CI 1.2 -3.8)]; previous blood transfusion [OR: 3.7 (95 percent CI 1.4 - 9.5)]; and injection drug use [OR: 22.6 (95 percent CI 4.2 - 119.6)]. CONCLUSION: Injection drug use was an independent risk factor for HCV infection among chronic renal disease patients on HD.

Infecção pelo vírus da hepatite c em pacientes em hemodiálise: prevalência e fatores de risco

CONTEXTO: Doentes com doença renal crônica em tratamento hemodialítico apresentam risco aumentado de aquisição do vírus da hepatite C (VHC). Elevadas taxas de prevalência têm sido detectadas em unidades de diálise do mundo inteiro. Estudos recentes têm demonstrado que a infecção pelo VHC interfere de forma negativa na sobrevida dos pacientes em hemodiálise e naqueles submetidos ao transplante renal. OBJETIVOS: Determinar a prevalência e os fatores de risco da infecção pelo VHC em pacientes submetidos a hemodiálise. MÉTODOS: Realizou-se estudo transversal entre janeiro e dezembro de 2007. Neste período, 236 pacientes em hemodiálise foram testados pelo ELISA de terceira geração. Os casos positivos foram submetidos a pesquisa qualitativa do HCV-RNA pelo método de PCR. Consideraram-se como portadores de infecção pelo VHC aqueles pacientes com anti-VHC e HCV-RNA positivos. Dosagens mensais de ALT e a média do valor de 12 meses foram obtidas em 195 pacientes. Do total de pacientes, 208 (88,1 por cento) responderam ao questionário padronizado visando a identificação de fatores de risco associados à infecção pelo VHC. RESULTADOS: A prevalência de pacientes anti-VHC positivos encontrada entre os 236 testados foi de 14,8 por cento (35/236); destes, a pesquisa do HCV-RNA foi positiva em 71,6 por cento (25/35). Portanto, a prevalência da infecção crônica pelo VHC foi de 10,6 por cento (25/236) dos pacientes. Pela análise bivariada, os principais fatores de risco associados à infecção pelo VHC foram o tempo de hemodiálise, o número de transfusões de sangue, a realização prévia de diálise peritonial e história de doença sexualmente transmissível. Contudo, após análise multivariada, somente o tempo de hemodiálise e história de doença sexualmente transmissível foram significativamente associados à infecção pelo VHC. Pacientes com mais de 10 anos de hemodiálise apresentaram risco de aquisição do VHC 73,9 (IC de 17,5 a 311,8) vezes maior quando comparados ...

CONTEXT: Chronic renal disease patients on hemodialysis are at increased risk of infection by hepatitis C virus (HCV). High prevalence rates have been reported from dialysis units worldwide. Recent studies have shown an inverse relation between HCV infection and life expectancy of patients on hemodialysis and those undergoing renal transplant. OBJECTIVES: Assess the prevalence of and risk factors for HCV infection in patients undergoing hemodialysis. METHODS: A cross-sectional study was undertaken from January to December, 2007. During this period, 236 patients were tested for anti-HCV antibodies with third generation ELISA. Those who tested positive further underwent qualitative PCR testing for HCV-RNA. A subject was considered HCV-infected if both tests (anti-HCV and HCV-RNA) were positive. Monthly serum ALT and the mean for the 12-month period were obtained from 195 patients. Two hundred eight (88.1 percent) patients answered a standardized questionnaire aiming to identify risk factors for HCV infection. RESULTS: Of the 236 subjects studied, 14.8 percent (35/236) tested positive for anti-HCV antibodies. Of these, 71.6 percent (25/35) tested positive for HCV-RNA. Chronic HCV infection was thus prevalent in 10.6 percent (25/236). Bivariate analysis showed time on hemodialysis, number of blood transfusions, previous peritoneal dialysis and previous sexually transmitted diseases to be the main risk factors for HCV infection. Yet multivariate analysis showed that just time on hemodialysis and previous sexually transmitted diseases were significantly associated with HCV infection. Patients on hemodialysis for over 10 years were 73.9 (CI 17.5-311.8) times as likely to have acquired HCV, compared with those on hemodialysis for up to 5 years. Patients with previous sexually transmitted diseases had a 4.8 times higher risk of HCV infection compared with those without previous sexually transmitted diseases. Mean serum ALT was significantly higher ...

Comparison of the effectiveness of initial combined antiretroviral therapy with nelfinavir or efavirenz at a university-based outpatient service in Brazil

Since there are some concerns about the effectiveness of highly active antiretroviral therapy in developing countries, we compared the initial combination antiretroviral therapy with zidovudine and lamivudine plus either nelfinavir or efavirenz at a university-based outpatient service in Brazil. This was a retrospective comparative cohort study carried out in a tertiary level hospital. A total of 194 patients receiving either nelfinavir or efavirenz were identified through our electronic database search, but only 126 patients met the inclusion criteria. Patients were included if they were older than 18 years old, naive for antiretroviral therapy, and had at least 1 follow-up visit after starting the antiretroviral regimen. Fifty-one of the included patients were receiving a nelfinavir-based regimen and 75 an efavirenz-based regimen as outpatients. Antiretroviral therapy was prescribed to all patients according to current guidelines. By intention-to-treat (missing/switch = failure), after a 12-month period, 65 percent of the patients in the efavirenz group reached a viral load <400 copies/mL compared to 41 percent of the patients in the nelfinavir group (P = 0.01). The mean CD4 cell count increase after a 12-month period was also greater in the efavirenz group (195 x 10(6) cells/L) than in the nelfinavir group (119 x 10(6) cells/L; P = 0.002). The efavirenz-based regimen was superior compared to the nelfinavir-based regimen. The low response rate in the nelfinavir group might be partially explained by the difficulty of using a regimen requiring a higher patient compliance (12 vs 3 pills a day) in a developing country.

Weight-based combination therapy with peginterferon alpha-2b and ribavirin for Naïve, relapser and non-responder patients with chronic hepatitis C

Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54 percent for naïve, 62 percent for relapser and 38 percent for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67 percent) compared to those with genotype 1 (45 percent). In relapsers and non-responders, SVR was, respectively, 69 percent and 24 percent in patients with genotype 1 and 43 percent and 73 percent in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (< 65 kg, 65-85 kg and > 85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78 percent, 81 percent and 58 percent of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63 percent, 67 percent and 61 percent, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13 percent of the patients, due to loss to follow-up, hematological abnormalities or depression.

Hepatitis C en Chile: Magnitud del problema / Hepatitis C in Chile: Burden of the disease

Hepatitis C virus-associated chronic hepatitis is one of the most important causes of liver-related mortality and morbidity worldwide. This review analysis the available clinical and epidemiological information about this disease in Chile and compares it with data available from Latin America and other countries. Chronic hepatitis C seroprevalence in the general Chilean population is 1.15% by ELISA III and 0.85% by recombinant immunoblot assay (RIBA). Mortality due to cirrhosis (all causes) in Chile is one of the highest in the world. We show indirect evidence that chronic hepatitis C may account for a significant proportion of these deaths. The disease is the most common cause for liver transplantation in adults. Based on the available information, we conclude that chronic hepatitis C is an important cause of disease and mortality in Chile.