Redução da resistência à insulina após resposta virológica sustentada com agentes antivirais diretos: nem toda população melhora / Insulin resistance reduction after sustained virological response with direct acting antiviral: not every population improves

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is a serious public health problem, that affects approximately 170 million people worldwide. Chronic HCV infection is associated with hepatic insulin resistance and an increased risk of diabetes HCV-infected patients has been well documented. OBJECTIVE: To assess the homeostasis model assessment of insulin resistance (HOMA-IR) index in patients treated with direct acting antiviral (DAAs) medication in the sustained virological response (SVR), categorized by the presence or absence of cirrhosis. METHODS: A prospective study was conducted. Data were collected at the beginning of treatment (t-base) and in the twelfth week after the completion of treatment (t-SVR12). The inclusion criteria were presence of: HCV infection (RNA-HCV positive), age ≥18 years, completion of DAAs' therapy, and presence of diabetes with use of oral hypoglycemic agents. All samples were collected during the study period. The exclusion criteria were: presence of HBV/HIV co-infection, hepatocellular carcinoma at baseline, diabetic patients taking insulin and transplanted patients (liver/kidney). Fibrosis was assessed by hepatic elastography or biopsy (METAVIR). Cirrhosis was determined by clinical results or imaging. HOMA-IR was calculated as fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5) The patients were divided into two groups: the general study population (all patients, including the diabetic patients) and the special population (patients with normal values of HOMA-IR, which is >2.5, and without diabetes). The delta HOMA-IR value was calculated as: HOMA-IR at t-base - HOMA-IR at t-SVR12. For the descriptive statistical analysis, the paired t-test and generalized linear model assuming the log binding function were performed. A P value of < 0.05 was considered significant. RESULTS: We included 150 patients, and 75 were cirrhotic. The mean age was 55.3±9.97 and body mass index was 27.4±5.18. Twenty-two (14.67%) were diabetic patients using oral hypoglycemic agents, and 17 (11%) were cirrhotic. In the general study population, the mean glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. Delta HOMA-IR was negative at t-SVR12, but there was no significant difference. Excluding diabetic patients and those with normal HOMA-IR values (<2.5), mean glucose, insulin and HOMA-IR decreased at t-SVR12. Delta HOMA-IR decreased significantly at t-SVR12 (P: 0.02). CONCLUSION: In the general population, glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. In the special population, glucose, insulin, HOMA-IR and Delta HOMA-IR decreased at t-SVR12.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (VHC) é um grave problema de saúde pública, que afeta aproximadamente 170 milhões de pessoas no mundo. A infecção crônica pelo VHC está associada à resistência à insulina hepática e a um risco aumentado de diabetes. Os doentes infetados pelo VHC foram bem documentados. OBJETIVO: Avaliar o modelo de avaliação da homeostase do índice de resistência à insulina (HOMA-IR) em pacientes tratados com medicação antiviral de ação direta na resposta virológica sustentada (RVS), categorizada pela presença ou ausência de cirrose. MÉTODOS: Foi realizado um estudo prospectivo. Os dados foram coletados no início do tratamento (t-base) e na décima segunda semana após o término do tratamento (t-RVS12). Os critérios de inclusão foram presença de: infecção pelo VHC (RNA-VHC positivo), idade ≥18 anos, conclusão da terapia de antivirais de ação direta e presença de diabetes com uso de hipoglicemiantes orais. Todas as amostras foram coletadas durante o período do estudo. Os critérios de exclusão foram: presença de coinfecção VHB/HIV, carcinoma hepatocelular no início do estudo, pacientes diabéticos em uso de insulina e pacientes transplantados (fígado/rim). A fibrose foi avaliada por elastografia hepática ou biópsia (METAVIR). A cirrose foi determinada por resultados clínicos ou exames de imagem. O HOMA-IR foi calculado como insulinemia de jejum (μU/mL) x glicemia de jejum (mmol/L) /22,5). Os pacientes foram divididos em dois grupos: a população geral do estudo (todos os pacientes, incluindo os diabéticos) e a população especial (pacientes com valores normais de HOMA-IR, que é <2,5 e sem diabetes). O valor do delta HOMA-IR foi calculado como: HOMA-IR no t-base - HOMA-IR no t-RVS12. Para a análise estatística descritiva, foram utilizados o teste t pareado e o modelo linear generalizado, assumindo a função de ligação logarítmica. Um valor de P<0,05 foi considerado significativo. RESULTADOS: Foram incluídos 150 pacientes e 75 eram cirróticos. A idade média foi de 55,3±9,97 e o índice de massa corpórea foi de 27,4±5,18. Vinte e dois (14,67%) eram pacientes diabéticos em uso de hipoglicemiantes orais e 17 (11%) eram cirróticos. Na população geral do estudo, os valores médios de glicose e HOMA-IR aumentaram na t-SVR12, mas a insulina diminuiu. O delta HOMA-IR foi negativo em t-SVR12, mas não houve diferença significativa. Excluindo pacientes diabéticos e aqueles com valores normais de HOMA-IR (<2,5), a média de glicose, insulina e HOMA-IR diminuiu no t-RVS12. O delta HOMA-IR diminuiu significativamente em t-RVS12 (P: 0,02). CONCLUSÃO: Na população geral, os valores de glicose e HOMA-IR aumentaram no t-RVS12, mas a insulina diminuiu. Na população especial, glicose, insulina, HOMA-IR e delta HOMA-IR diminuíram no t-RVS12.

Nuevos progresos en el enfrentamiento a la hepatitis C / New progresses in hepatitis C management

RESUMEN El virus de la hepatitis C es la principal infección trasmitida por los derivados de la sangre en los Estados Unidos, con 3.2 millones de individuos infectados. El alfa interferón inyectable ha sido históricamente la piedra angular en la terapia del virus de hepatitis C. Se revisaron las publicaciones los trabajos publicados en Medline, Scielo, PubMed, e Hinari, hasta comienzos del año 2016. Las principales palabras clave utilizadas fueron virus de la hepatitis C, hepatitis C crónica, Interferón, antivirales. Recientes adelantos han llevado a la disponibilidad de nuevos medicamentos antivirales, que con el desarrollo de nuevas terapias orales libres de interferón han convertido la terapia del virus de la hepatitis C más eficaz además de simplificar los regímenes del tratamiento. Aunque estos regímenes de tratamiento aún permanecen complicados, las nuevas recomendaciones y guías evolucionan rápidamente. El rápido desarrollo de nuevas terapias para la hepatitis C, han logrado métodos más eficaces con menos reacciones adversas que optimizan el tratamiento de estos enfermos (AU).

ABSTRACT The hepatitis C virus is the main infection transmitted by blood products in the United States, with 3.2 million of infected individuals. The injected alpha interferon has historically been the key stone in the therapy of the hepatitis C virus. The works published in Medline, Scielo, PubMed and Hinary until the beginning of 2016 were reviewed. The main used key words were HVC, cronic hepatitis C, interferon, antivirals. Recent advances have led to the availability on new antiviral drugs, developing new interferon-free oral therapies that make the therapy of hepatitis C virus more efficacious and make easier the treatment regimens. Although these treatment regimens are still complicated, the new recommendations and guidelines evolve quickly. The fast development of new therapies against hepatitis C has led to more efficacious methods with less adverse reactions, optimizing the treatment of these patients (AU).

To determine correlation between biochemical parameters of nutritional status with disease severity in HCV related liver cirrhosis

Objective: To identify correlation between biochemical parameters of nutritional status with disease severity in HCV related liver cirrhosis in patients attending tertiary care hospital

Methods: Total 259 HCV related liver cirrhosis patients who attended the outpatient department of KRL Hospital, Islamabad from June 2016 to January 2018 were included in this crosssectional study. HCV status was confirmed with PCR. Cirrhosis was preestablished by ultrasound, while cirrhosis severity was gauged by CTP score. Biochemical parameters for nutrition status included serum albumin, creatinine, cholesterol, LDL, HDL, triglycerides, hemoglobin, ferritin, sodium, potassium, magnesium and calcium. Other demographic and clinical data were also recorded

Results: The mean age of patients was 58.73 +/- 6.04 years with 57.1% being males. The average BMI was 22.72 +/- 1.69 kg/m[2]. Majority patients i.e. 123 [47.5%] belonged to CTP-A, 67 [25.9%] were in CTP-B and 69 [26.6%] in CTP-C groups. Significant negative correlations of cirrhosis severity were established with BMI, albumin, creatinine, cholesterol, LDL, TG, HDL, hemoglobin, sodium and magnesium indicative of malnutrition. Analysis of biochemical parameters amongst individual cirrhosis groups revealed significant negative correlation across the same factors in group CTP-C, while CTP-A correlated positively with these parameters. The only significant correlation found in CTP-B was with albumin, HDL, hemoglobin, sodium and magnesium

Conclusion: Considering limitations of standard ways alone to assess malnutrition in liver cirrhosis, biochemical parameters are valid to aid in diagnosing malnutrition

Distribution of hepatitis C virus genotypes in patients with major beta-thalassemia in Mashhad, Northeast Iran

Background: Hepatitis C virus [HCV] is considered to be the major cause of post-transfusion hepatitis in patients with thalassemia. We aimed to determine the HCV prevalence, genotypes, and viral load among patients with major beta-thalassemia in Mashhad, Iran

Methods: Medical records of all 550 patients with major beta-thalassemia who referred to Thalassemia-Hemophilia Center of Mashhad [Sarvar Clinic] were reviewed from October to November 2011. Plasma samples of the patients were tested for the presence of anti-HCV antibodies by enzyme linked immunosorbent assay. Real-time polymerase chain reaction [PCR] was used to determine viral genotype and HCV RNA titer

Results: HCV antibodies were detected in 37 individuals [6.73%] including 17 men and 20 women with mean age of 25.2 +/- 8.4 years. The PCR analysis was performed for 27 patients, of whom HCV RNA was detected in 17 patients [63.0%]. Viral titers were investigated in 14 subjects and a high viral load more than 600000 copies/mL was observed in 6 patients [42.9%]. The most prevalent genotypes were 3a [50.0%] followed by 1a [37.5%]. No significant correlation was found between genotype and age, sex, serum ferritin, liver tests, and HCV RNA titer

Conclusion: HCV infection among patients with thalassemia is more common than general population in Mashhad, northeast Iran. The dominant HCV subtype is 3a followed by 1a. These findings could help health authorities to provide preventive measures, and practitioners to choose the right protocol of treatment for the patients

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.

Coinfección virus de inmunodeficiencia humana-virus de la Hepatitis C: hacia un nuevo escenario terapéutico / Human Immunodeficiency Virus-Hepatitis C virus coinfection: towards a new therapeutic scenario

Introducción: Las terapias contra el virus de la Hepatitis C han evolucionado vertiginosamente con el desarrollo de los antivirales de acción directa (AADs). Los nuevos regímenes han conseguido igualar las tasas de respuesta al tratamiento en los monoinfectados y los coinfectados con VIH, una población tradicionalmente difícil de tratar debido a la elevada morbimortalidad hepática y sistémica, reacciones adversas e interacciones medicamentosas. Objetivo: Analizar las opciones farmacoterapéuticas más modernas disponibles para los pacientes coinfectados con VIH y VHC, con énfasis en los nuevos antivirales de acción directa, a fin de ofrecer una herramienta útil en el abordaje terapéutico en estos pacientes. Material y métodos: Se revisaron artículos originales, ensayos clínicos y revisiones sistemáticas hasta septiembre de 2016, bases de datos internacionales de interacciones medicamentosas y Guías de Práctica Clínica actualizadas. Desarrollo: Las terapias contra el virus de la Hepatitis C (VHC) han evolucionado vertiginosamente con el desarrollo de los antivirales de acción directa (AADs). Los nuevos regímenes han conseguido igualar las tasas de respuesta al tratamiento en los monoinfectados y los coinfectados con VIH, una población tradicionalmente difícil de tratar que, además, asociaba una elevada morbimortalidad hepática y sistémica, más reacciones adversas y complejas interacciones medicamentosas. Conclusiones: En este nuevo escenario es fundamental dedicar esfuerzos a identificar el elevado porcentaje de infectados no diagnosticados, potenciales interacciones, especialmente con fármacos para patologías asociadas al envejecimiento de los pacientes, reacciones adversas a medio-largo plazos y desarrollo de resistencias, además de garantizar la cobertura universal en todos los contextos clínicos(AU)

Introduction:Therapies for hepatitis C virus (HCV) have rapidly evolved with the development of direct-acting antiviral agents. New regimens, achieve an equate response rates to treatment in cases of HCV mono-infected and HIV/HCV co-infected; a population traditionally difficult to treat due to a high hepatic and systemic morbidity-mortality, adverse reactions and drug interactions. Objective: To analyse the current Pharma-therapeutic options available for co-infected HIV-HCV patients, with emphasis I the new direct-acting antiviral agents, in order to offer a useful tool for the therapeutic approach in these patients. Material and Methods: Original articles, clinical studies and systematic reviews until September 2016 were carried out, as well as international drug interactions databases and updated Practical Guidelines. Development: Therapies for hepatitis C virus (HCV) have rapidly evolved with the development of direct-acting antiviral agents. New regimens achieve an equate response rates to treatment in HCV mono-infected and HIV/HCV co-infected; a population traditionally difficult to treat, which also associate a high hepatic and systemic morbidity-mortality, adverse reactions and complex drug interactions. Conclusions: In this new scenario efforts must be addressed to identify the high percentage of undiagnosed patients; potential interactions, especially with drugs related with patient aging; medium and long-term adverse reactions and development of drug resistances, as well as to guarantee universal coverage in all clinical contexts(AU)

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Correlation between hepatitis C viral load and hepatitis C Core antigenaemia among Egyptians

Hepatitis C virus [HCV] infection is widespread in Egypt. This study compared HCV RNA with HCVcAg for the detection and quantification of viraemia among a sample of Egyptians. Sera from 80 suspected HCV-positive individuals were tested simultaneously for HCV-RNA load using real-time polymerase chain reaction [PCR] and HCVcAg level using ELISA. Of the 80 samples, 25% were HCV-RNA-negative. HCVcAg was detected in all samples: range 0.4-2462 ng/mL, mean 460 [SD 506] ng/mL. The sensitivity and specificity of HCVcAg were 96.7% and 90.9%, respectively. There was a significant correlation between serum HCV-RNA and HCVcAg levels [r = 0.4, P < 0.0001]. HCV-RNA remains the gold standard for diagnosis of active HCV infection but HCVcAg can be used where PCR is not available

Evaluation of serum levels and significance of soluble CD40 ligand in screening patients with hepatitis C virus-related hepatocellular carcinoma

The study's objective was to evaluate the clinical significance of sCD40L in HCV- associated hepatocellular carcinoma [HCV-HCC] patients. Sera concentration of circulating sCD40L and IL-10 were assayed using ELISA in 30 HCV positive patients with HCC, 30 HCV-positive patients with liver cirrhosis and 30 age-matched healthy volunteers with negative anti-HCV-Ab as a control group. Serum sCD40Lshowed statistically-significant high levels in HCV-HCC patients compared to HCV-cirrhotic patients and normal controls [P < 0.001]. Serum sCD40L had higher diagnostic value in HCC patients compared with serum AFP. High sensitivity and specificity of sCD40L was observed compared to AFP [90%, 86.7% and 83% and 80% respectively]. Significant positive correlation was detected between serum sCD40L and IL-10[r = 0.85 P < 0.001], AFP [r = 0.62 P < 0.05] and tumour staging [r = 0.5 P < 0.05]. The study concluded that sCD40L is a valuable diagnostic tool in early diagnosis and screening for HCV and HCC as well as routine follow up of HCV cirrhosis patients. Assessment of serum IL-10 levels in HCV patients may provide a possible predictive marker for disease progression

Prevalence and correlates of hepatitis C virus infection among inmates at two New York State correctional facilities

Previous studies have reported decreasing hepatitis C virus [HCV] infection rates in the general population. However, differential susceptibility in institutionalized populations suggest that HCV infection is even more prevalent in prison populations than previously reported yet, routine screening for HCV infection among prisoners is not generally available. We estimated the HCV prevalence and identified associated exposures at two maximum-security prisons using data obtained from 2788 inmates from the Risk Factors for Spread of Staphylococcus aureus in Prisons Study in New York, which recruited participants from January 2009 and January 2013. HCV prevalence was 10.1% [n = 295]; injection drug use, injection drug use sex partners, and HIV diagnosis exhibited the strongest associations with HCV infection in multivariable models, adjusting for covariates. Taken together, the findings of the present study provide an updated estimate of HCV prevalence and suggest that incarcerated populations represent a declining yet significant portion of the hepatitis epidemic

CD8+T cell activation associated with viral replication in chronic infection

PD-1 expression is controlled during T-cell activation. PD-1 has an important role in regulating immune response as well as tolerance. During chronic hepatitis C virus [HCV] infection there is high level of PD-1 expression on exhausted CD8+T cells. There is also reduced expression of T-bet. T-bet is identified as a transcriptional repressor of Pdcd1. The study will attempt to find out the level of expression of PD-1 on peripheral CD8 + T-cells, associated with chronic HCV infection. Fifty patients with chronic hepatitis C virus infection [CHCV], whose age ranged between [16-59] years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before Interferon and ribavirin therapy, and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations. CBCs and analysis of the expression of surface markers on CD8+T cells and PD-1. Our results suggested that increased expression of PD-1 cells was an additional inhibitory mechanism that contributed to virus-specific CD8 + T cell exhaustion in chronic hepatitis C virus [CHCV] infected patients. Our study concluded that there's significant increase in PD-1 expression of circulating HCV-specific CD8 + T cells in CHCV patients. The blockade of the inhibitory receptors [PD-1] programmed cell death is considered as a novel strategy for the treatment of chronic HCV infection

Aspectos clínicos y epidemiológicos de pacientes con carcinoma hepatocelular en dos centros de referencia de Venezuela / Clinical and epidemiological aspects of patients with hepatocellular carcinoma in two reference centers Venezuela

El carcinoma hepatocelular (CHC) es la neoplasia primaria del hígado más frecuente, constituyendo un problema mundial de salud pública por su alta prevalencia y tasa de mortalidad. Evaluar las características clínicas y epidemiológicas de los pacientes con carcinoma hepatocelular. Estudio de casos consecutivos con revisión retrospectiva de los registros médicos de pacientes con diagnóstico de CHC que acudieron a la consulta de hepatología de dos centros caraqueños entre 1997 y 2011. Se evaluaron características clínicas, epidemiológicas y de estadiaje según Barcelona Clinic Liver Cancer, BCLC. Se incluyó 116 pacientes con diagnóstico de CHC. La edad media fue 61,34 ± 12,02 años, 75% eran hombres y 89,7% de los pacientes tenían cirrosis hepática subyacente, siendo confirmada histológicamente en 33,7%. El 70,7% de los pacientes tenían alguna complicación asociada a hipertensión portal. El virus de la hepatitis C (VHC) constituyó la principal etiología de enfermedad hepática (31%), alcohol (21,6%), virus de la hepatitis B, VHB (14,7%) y enfermedad hepática grasa no alcohólica (14,7%). El hepatocarcinoma fue diagnosticado más frecuentemente en pacientes con cirrosis por HBV 15,56%. El 56% de los casos tenían niveles de alfafetoproteína mayores de 300 ng/ml. El lóbulo derecho fue la localización más frecuente (64,7%) y 79,3% de las lesiones mostraron patrón vascular típico en los estudios radiológicos. El estadio tumoral según los criterios de Barcelona Clinic Liver Cancer (BCLC) fueron estadio C (37,9%) D (25,9%), B (24,1%), A (7,8%) y 0 (2,6%). La infección por HCV es la etiología más frecuente de cirrosis hepática en pacientes con CHC, pero la infección por VHB tiene mayor impacto en términos relativos. El diagnóstico se hace en forma tardía (estadios intermedios o avanzados), siendo necesario intensificar medidas de pesquisa en estos pacientes

The hepatocellular carcinoma (HCC) is the main primary liver neoplasia and is a public health problem in the world due to high prevalence and mortality. Evaluate clinical and epidemiological characteristics in patients with Hepatocellular carcinoma. A retrospective analysis of a prospectively maintained database of 116 patients with diagnosis of HCC in two centers of Caracas between 1997 and 2011 was conducted. We evaluated epidemiological, clinical, biochemical and tumor aspects according to Barcelona Clínic Liver Cancer in patients with HCC. Mean age was 61.34 ± 12.02 years, 75% were male and 89.7% of patients had liver cirrhosis. Portal hypertension complications (ascites, hepatic encephalopathy, esophageal varices) were present in 70.7% of patients. Hepatitis C virus (HCV) was the main etiology of hepatic disease (31%) followed by alcohol (21.6%), hepatitis B virus (14.7%) and non alcoholic steatohepatitis (14.7%). HCC was more frequent in patients with cirrhosis associated to HBV infection. The 56% of patients had alpha-fetoprotein levels higher than 300 ng/ml. The 64.7% of tumors were localized in the right lobe of liver and 79.3% of tumor lesions demonstrated typical pattern in radiologic studies. The most patients had advanced disease according to Barcelona Clinic Liver Cancer (BCLC) staging classification (Stage C, 37.9%; stage D, 25.9%; stage B, 24.1%; stage A, 7.8% and stage 0, 2.6%). HCV infection was main cause of cirrhosis in patients with HCC, but HBV infection had higher impact in these patients. Our study showed that the diagnosis of these patients undergo late and is very important intensify screening measures in patients with liver cirrhosis

Avaliação da presença de mutações de resistência no gene da NS5B e do prognóstico da infecção pelo HCV através da IL-28B em pacientes monoinfectados com HCV no RJ / Evaluation of resistance mutations presence in the NS5B gene and prognosis of HCV infection throught IL-28B in HCV monoinfected patients of RJ

Estima-se que a prevalência global da população mundial com hepatite C é de 3%. Pouco se sabe sobre a resposta ao tratamento com respeito à resistência viral. Algumas mutações no fragmento de 109 aminoácidos da NS5B são associadas com resistência ao interferon (IFN) e ribavirina (RBV). Estudos moleculares e clínicos identificaram fatores associados com o hospedeiro e vírus relacionados associada com a resposta ao tratamento, tal como o gene que codifica a IL-28B. Este estudo foi dividido em duas fases, cujos objetivos foram caracterizar a frequência de mutações que conferem resistência ao HCV e avaliar a relevância das mutações em pacientes Respondedores (R) ou Não Respondedores (NR) ao tratamento e caracterizar geneticamente as populações sobre polimorfismos genéticos nos SNPs da IL-28B em relação ao prognóstico da resposta ao tratamento. As amostras dos pacientes foram submetidas a testes de genotipagem e carga viral. As sequências geradas foram comparadas no BLAST e no banco de dados Los Alamos HCV. Realizamos o alinhamento das sequências homólogas e as mutações identificadas. Com base no genótipo e carga viral determinamos a classificação dos pacientes de acordo com a resposta à terapia. O DNA genômico foi isolado a partir de sangue periférico para a realização da tipagem de SNPs de IL-28B. A metodologia utilizada foi de PCR em tempo real utilizando sondas TaqMan SNP específico. A análise dos dados foi realizada utilizando GraphPad Prism com qui-quadrado, risco relativo (RR), Odds Ratio (OR) e intervalo de confiança de 95%, com um nível de significância de P <0,05. Foi encontrado na primeira fase deste estudo uma taxa significativa mutações associadas ao tratamento nas amostras estudadas. A prevalência de mutações associadas à resistência ao IFN e RBV bem como a novos medicamentos antivirais localizados no fragmento de 109 aminoácidos da NS5B foi examinado em 69 indivíduos infectados naïve no Rio de Janeiro, Brasil. Na segunda fase, as mutações foram ...

It is estimated that the overall prevalence of the average world population with hepatitis C is 3%. Little is known about the treatment response with respect to viral resistance. Some mutations in the 109-aminoacid fragment of NS5B are associated to Interferon (IFN) and Ribavirin (RBV) resistance. Molecular and clinical studies have identified factors associated with the host and related viruses associated with response to treatment, as the gene encoding IL-28B. This study was divided into two phases whose objectives were to characterize the frequency of mutations conferring resistance to HCV viral evaluating the relevance of these in Responders (R) or Non-Responders (NR) patients to treatment and to characterize genetically the populations regarding genetic polymorphisms SNPs IL-28B in relation to prognosis of response to treatment for HCV. Patient samples were subjected to tests for genotyping and viral load. The sequences generated were compared in the BLAST and the Los Alamos database HCV. We conducted the alignment of homologous sequences and mutations identified. Based on virological parameters genotype and viral load determined the classification of patients according to response to therapy. Genomic DNA was isolated from peripheral blood for carrying out the typing of SNPs of IL-28B. The methodology used was real-time PCR using TaqMan probes specific SNPs. Data analysis was performed using GraphPad Prism with chi-square, relative risk (RR), Odds Ratio (OR) and confidence interval of 95% with a significance level of P <0.05. To study these biological parameters we associated the responsive patients, non-responders, the viral load, genotype, and IL-28B polymorphism to treatment outcome. We found in the first phase of this study a significant rate of treatment-associated mutations in the samples studied. The prevalence of mutations associated to resistance to interferon and ribavirin (IFN/RBV) as well new antiviral drugs located in the 109 aminoacid ...

Influência do polimorfismo genético de citocinas na hepatite C crônica em uma população do Rio de Janeiro / Influence of cytokine genetic polymorphism on chronic hepatitis C in a population of Rio de Janeiro

A infecção pelo vírus da hepatite C (VHC) é uma das mais comuns infecções ao redor do mundo. Aproximadamente, 20% dos pacientes infectados eliminam espontaneamente o vírus, porém a maioria dos indivíduos infectados desenvolve infecção crônica com amplo espectro de lesões hepáticas, desde inflamação leve até cirrose. A resposta imune do hospedeiro exerce grande influência sobre o desfecho da infecção pelo VHC. O objetivo deste trabalho foi analisar a influência dos polimorfismos genéticos de citocinas na susceptibilidade ou persistência da infecção por VHC e no clareamento espontâneo em uma amostra de pacientes da população do Rio de Janeiro (Brasil). Os polimorfismos genéticos das citocinas TNFA (-308), TGFB1 (codon 10 e 25), IL10 (-1082, -592), IL6 (-174) e IFNG (+874) foram analisados por PCR-SSP em 245 pacientes com hepatite C crônica (HCC), 41 pacientes que alcançaram o clareamento viral espontâneo e 189 indivíduos controle saudáveis. Além disso, os polimorfismos próximos ao gene da citocina IL28B (rs12979860, rs12980275 e rs8099917) foram analisados por PCR em tempo real em todos os grupos...

Hepatitis C virus infection is one of the most common blood-borne infections worldwide. Approximately, 20% of infected patients successfully eliminate the virus, whereas the majority of patients develop chronic infection with a wide spectrum of liver lesions, ranging from a minimal inflammation to cirrhosis. The host's immune response is an important correlate of HCV infection outcome and disease progression. The aim of this study was to explore the possibility of the inheritance of cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV clearance in a sample of Rio de Janeiro (Brazil) population. Genetic polymorphisms in the cytokines TNFA (-308), TGFB1 (codon 10 and 25), IL10 (-1082, -592), IL6 (-174) and IFNG (+874) were analyzed by polymerase chain reaction-sequence-specific primer (SSP) in 245 chronic hepatitis C (HCC) patients, 41 spontaneous recovery (SR) patients and 189 healthy volunteers. Further, IL28B (rs12979860, rs12980275 and rs8099917) were assessed by real-time PCR in all groups...

Análise de quasiespécies do vírus da hepatite C (HCV) e implicação na transmissão intrauterina / Analysis of quasispecies of the hepatitis C virus (HCV) and involvement in transmitting utero

A transmissão materno-infantil (TMI) é a causa mais comum de infecção pelo vírus da hepatite C (HCV) entre as crianças. Objetivo: Esse estudo teve como objetivo avaliar fatores virais implicados na TMI do HCV. Materiais e métodos: Quatro gestantes e um par mãe-recém-nascido (RN), todos infectados pelo HCV, foram incluídos neste estudo. Sequências das regiões 5’UTR, E1, HVR1, E2 e NS5B foram obtidas através de sequenciamento direto do produto do PCR e clonagem. A diversidade quasiespécie foi analisada utilizando-se diferentes parâmetros (taxa de clonotipos, frequência de mutações, Pn e entropia de Shannon normalizada), comparando (1) grupos TMI+ e TMI-, e (2) par mãe-RN. Um framework foi usado para avaliar a associação entre a frequência dos nucleotídeos e a TMI. Resultados: Dois casos de TMI foram identificados, mas apenas a amostra de um RN estava disponível. As cargas virais de todos os sujeitos estavam acima do limite de quantificação. Ambos os casos de TMI pertenciam ao genótipo 1a apenas este subtipo foi analisado subsequentemente. O sequenciamento direto dos produtos de PCR não representou, de maneira confiável, a complexidade quasiespécie e não foi utilizado. Não houve clonotipos coincidentes entre os grupos TMI+ e TMI-, exceto pela região 5’UTR. Em nível de aminoácido, mãe e RN compartilharam apenas do clonotipo predominante. Todos os clonotipos minoritários foram exclusivos. Foi observada maior diversidade quasiespécie nas regiões E2 e NS5B. A HVR1 apresentou a menor diversidade dentro da região codificante. A diversidade quasiespécie do grupo TMI+ foi sempre maior do que aquela vista no grupo TMI-; no entanto, não houve significância estatística. Trinta e cinco mutações na região codificante foram associadas significativamente com a TMI. Dados do par mãe-RN sugerem que a transmissão intrauterina ocorreu em um momento inicial da gestação e que o vírus provavelmente atravessou o tecido placentário, levando a um gargalo de garrafa. Conclusões: A diversidade quasiespécie não foi associada à TMI, mas a presença de mutações ao longo da região codificante sugere que o genoma completo contribui para a capacidade de transmissão intrauterina. São necessários estudos adicionais para determinar se essas variantes podem ser úteis para predizer a TMI.

Tratamiento antirretroviral en pacientes coinfectados por HIV/HCV / Antiretroviral treatment for HIV/HCV co-infected patients

La hepatotoxicidad asociada al tratamiento antirretroviral complica el manejo de los pacientes coinfectados por HIV y HCV. Existen diferentes patrones de toxicidad hepática asociadas a las drogas antirretrovirales que deben ser reconocidos por los médicos tratantes, como así también las interacciones con las drogas utilizadas para el tratamiento de la infección por HCV. En la presente revisión se describen la toxicidad hepática de las drogas antirretrovirales, incluyendo las incorporadas recientemente, y las indicaciones de tratamiento y esquemas más convenientes para esta población de personas viviendo con HIV/sida

Antiretroviral therapy-related hepatotoxicity complicates the management of HIV/HCV co-infected patients. There are different patterns of antiretroviral associated liver toxicity, which should be recognized by the physicians. Updated information regarding antiretroviral related hepatotoxicity (including the most recently licensed), treatment indication and the most convenient drugs combination for HIV/HCV patients are presented in this review

Prevalência de infecção pelo vírus da hepatite C (VHC)em gestantes e transmissão materno-infantil / Prevalence of infection with hepatitis C virus (HCV) in pregnant women and mother-child transmission

A transmissão materno-infantil (TMI) do vírus da hepatite C (VHC) ocorre em 4%-13% das gestações quando a mãe é infectada, e poucos estudos de prevalência foram realizados em gestantes no Brasil. O objetivo desta pesquisa foi determinar a prevalência de infecção e fatores associados à presença de infecção pelo VHC em gestantes, e determinar a taxa de TMI do VHC. O estudo foi realizado em Salvador, no período entre Maio de 2009 e Abril de 2011, na Maternidade Referência Professor José Maria Magalhães Netto. Todas as voluntárias que assinaram ao TCLE, tiveram seus prontuários revisados e tiveram amostra de soro coletada para a realização do teste rápido anti-VHC (Bioeasy), ELISA 3ª geração (Artech), e detecção do VHC-RNA Qualitativo e Quantitativo (AMPLICOR HCV TESTE, ROCHE versão 2.0). Em uma subamostra de gestantes selecionada aleatoriamente, realizouse entrevista para analisar fatores sócio-demográficos e de exposição ao VHC não disponíveis nos prontuários. A análise estatística descritiva e de associação foram realizadas utilizando o programa EPI Info 3.5.3 (CDC, Atlanta, GE, EUA). Foram incluídas no estudo 3.049 gestantes, sendo que 8 (0,26%; IC 95%: 0,12%-0,50%)foram soropositivos para o anti-VHC pelo ELISA e 6 (0,20%; IC 95%: 0,08%-0,41%) confirmaram viremia. Todos os VHC genotipados pertenceram ao genótipo 1, 1a ou 1b. Os principais fatores associados à infecção materna pelo VHC foram uso de drogas, tatuagem, e infecção por HIV (p < 0,05). Das 6 gestantes com HCV positivo, 2 (33,3%; IC 95%: 6,0%-73,8%) transmitiram o HCV para seus filhos. Em um dos casos de TMI, a mãe relatou ter feito uso de drogas injetáveis e inaláveis durante a gestação, possuía tatuagem e era portadora do HIV sob tratamento antiretroviral. O recém-nascido (RN) nasceu com idade gestacional (IG) de 38 semanas através de parto cesariano eletivo. No outro caso, a mãe relatou uso de drogas injetáveis e inaláveis, possuía piercing e tatuagem, mas não foi portadora de HIV. O RN nasceu com IG de 39 semanas, através de parto normal, com tempo de ruptura da bolsa de 15 horas. Concluímos que a prevalência de infecção pelo VHC entre gestantes é baixa quando comparada à da população em geral na mesma localidade, sendo associado a uso de drogas e tatuagem. A taxa de TMI do VHC encontrada foi maior do que o esperado. Assim, estudos mais amplos serão necessários.

A Case of Acute Disseminated Encephalomyelitis Associated with Hepatitis C Virus Infection

Acute disseminated encephalomyelitis (ADEM) is a monophasic autoimmune demyelinating disease of the central nervous system, which typically follows acute viral or bacterial infection or vaccination. We report a case of ADEM associated with hepatitis C virus (HCV) infection with positive serum and cerebrospinal fluid (CSF) anti-HCV antibody. After steroid treatment, neurologic symptoms were improved. Virus triggers autoimmunity or direct viral invasion plays a part in the genesis of ADEM. This is the first reported case of ADEM with anti-HCV antibody in the CSF.