Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil.

INTRODUCTION AND OBJECTIVES: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. MATERIALS AND METHODS: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). RESULTS: 3939 patients (60% males, mean age 58±10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. CONCLUSION: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.

RECOMMENDATIONS OF THE BRAZILIAN SOCIETY OF HEPATOLOGY FOR THE MANAGEMENT OF ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS.

Acute kidney injury is a common complication of cirrhosis, occurring in up to 20% of patients hospitalized with cirrhosis. This field is rapidly changing, with significant advances in classification, biomarkers and therapy over the last few years. On the behalf of the Brazilian Society of Hepatology, a panel of experts in Hepatology and Nephrology reviewed published evidence to integrate findings and develop the recommendations presented in this manuscript.

GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature.

BACKGROUND: The standard treatment of chronic hepatitis C is the administration of pegylated interferon α2a or α2b in combination with ribavirin, but adverse effects can be observed, as well as the high cost of this therapy. Therefore, there is interest in understanding the predictors of sustained virologic response, as the gamma glutamyltransferase. OBJECTIVE: To evaluate the serum levels of gamma glutamyltransferase as a predictor of response to treatment with pegylated interferon α and ribavirin in chronic hepatitis C. METHODS: This is a systematic review of literature, conducted by consulting PUBMED, LILACS, MEDLINE, SCOPUS, Cochrane electronic databases, and active search of articles selected between January 2000 and April 2013. RESULTS: A total of 4,785 titles were identified. Out of those material, following inclusion and exclusion criteria, 273 abstracts were selected, by two independent researchers. After reading those texts, the reviewers consensually included ten studies for systematization and classification, according to the criteria of the Oxford Scale. 1B studies are predominant (prospective cohort study - six studies). Rapid virologic response and early virological response were considered as estimates for the sustained virological response. The frequency of virologic response was identified in three studies and early virological response in two, with a total of 392 and 413 patients, respectively; sustained virologic response was reported in nine articles corresponding to 3,787 patients (76.5 %). CONCLUSION: Gamma glutamyltransferase is a predictor of sustained virologic response in the treatment of chronic hepatitis C with pegylated interferon α2a or α2b associated with ribavirin.

GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature / Impacto da gama glutamiltransferase na resposta terapêutica da hepatite C crônica: revisão sistemática da literatura

BackgroundThe standard treatment of chronic hepatitis C is the administration of pegylated interferon α2a or α2b in combination with ribavirin, but adverse effects can be observed, as well as the high cost of this therapy. Therefore, there is interest in understanding the predictors of sustained virologic response, as the gamma glutamyltransferase.ObjectiveTo evaluate the serum levels of gamma glutamyltransferase as a predictor of response to treatment with pegylated interferon α and ribavirin in chronic hepatitis C.MethodsThis is a systematic review of literature, conducted by consulting PUBMED, LILACS, MEDLINE, SCOPUS, Cochrane electronic databases, and active search of articles selected between January 2000 and April 2013.ResultsA total of 4,785 titles were iden tified. Out of those material, following inclusion and exclusion criteria, 273 abstracts were selected, by two independent researchers. After reading those texts, the reviewers consensually included ten studies for systematization and classification, according to the criteria of the Oxford Scale. 1B studies are predominant (prospective cohort study - six studies). Rapid virologic response and early virological response were considered as estimates for the sustained virological response. The frequency of virologic response was identified in three studies and early virological response in two, with a total of 392 and 413 patients, respectively; sustained virologic response was reported in nine articles corresponding to 3,787 patients (76.5 %).ConclusionGamma glutamyltransferase is a predictor of sustained virologic response in the treatment of chronic hepatitis C with pegylated interferon α2a or α2b associated with ribavirin.

ContextoO tratamento padrão da hepatite C crônica consiste na administração de interferon peguilado α2a ou α2b associado à ribavirina. Contudo, podem ser observados efeitos adversos além do alto custo desta terapêutica. Por isso há interesse no conhecimento dos fatores preditivos de resposta virológica sustentada como a gama glutamiltransferase.ObjetivoAvaliar os níveis séricos da gama glutamiltransferase como fator preditivo de resposta terapêutica com interferon peguilado α e ribavirina na hepatite C crônica.MétodosTrata-se de uma revisão sistemática da literatura, conduzida através de consulta às bases eletrônicas de dados PUBMED, LILACS, MEDLINE, SCOPUS e COCHRANE, e busca ativa das referências dos artigos selecionados, no período de janeiro de 2000 a abril de 2013.ResultadosForam identificados 4.785 títulos. Destes, seguindo os critérios de inclusão e exclusão, foram selecionados 273 resumos para a leitura por dois pesquisadores independentes. Após a leitura dos artigos, na íntegra e em consenso, os revisores incluíram dez estudos, para sistematização e qualificação, segundo os critérios da Escala de Oxford. Predominaram os estudos 1B A (Coorte prospectivo - seis estudos), publicações da Alemanha. A frequência de resposta virológica rápida foi identificada em três estudos e resposta virológica precoce em dois estudos, com um total de 392 e 413 pacientes respectivamente; a resposta virológica sustentada foi registrada em nove artigos correspondendo a 3.787 pacientes (76,5%).ConclusãoO nível sérico da gama glutamiltransferase é um fator preditivo de resposta virológica sustentada no tratamento da hepatite C crônica com interferon peguilado α2a ou α2b associado à ribavirina.

Metabolic syndrome and risk factors for non-alcoholic fatty liver disease.

CONTEXT: Non-alcoholic fatty liver disease (NAFLD), hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS) to non-alcoholic steatohepatitis (NASH). The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1) recognize patients with metabolic syndrome at high risk for NAFLD, 2) elucidate pathways common to other co-morbidities, 3) determine risk factors associated with a worse prognosis, 4) develop therapeutic strategies with goal of reducing risk factors, 5) apply acquired knowledge in public health policies focusing on preventive strategies.

Metabolic syndrome and risk factors for non-alcoholic fatty liver disease / Síndrome metabólica e fatores de risco para a doença hepática gordurosa não-alcoólica

CONTEXT: Non-alcoholic fatty liver disease (NAFLD), hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS) to non-alcoholic steatohepatitis (NASH). The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1) recognize patients with metabolic syndrome at high risk for NAFLD, 2) elucidate pathways common to other co-morbidities, 3) determine risk factors associated with a worse prognosis, 4) develop therapeutic strategies with goal of reducing risk factors, 5) apply acquired knowledge in public health policies focusing on preventive strategies.

CONTEXTO: A doença hepática gordurosa não alcoólica (DHGNA) vem sendo considerada a manifestação hepática da síndrome metabólica e a hepatopatia mais frequente da atualidade, sendo também a causa mais frequente de aumento das transaminases e de cirrose criptogênica. O maior aporte de ácidos graxos ao fígado e consequente aumento da beta-oxidação concorrem para formação de radicais livres, liberação de citocinas inflamatórias e graus variáveis de agressão hepatocítica, cuja expressão histológica pode variar da esteatose hepática (EH) à esteatohepatite não-alcoólica (EHNA), cuja diferenciação se faz necessária pelo risco potencial de progressão para cirrose e desenvolvimento do carcinoma hepatocelular. OBJETIVO: Revisar a literatura sobre os principais fatores de risco para a DHGNA no contexto da síndrome metabólica, com foco nos mecanismos subjacentes e nas estratégias de prevenção. MÉTODO: Foi realizada pesquisa bibliográfica no PubMed para identificar estudos que descrevessem a associação entre os fatores de risco para síndrome metabólica e a DHGNA, utilizando-se a combinação de descritores: "Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, metabolic syndrome and risk factors". Foram selecionados 96 estudos clínicos, experimentais, de cohort, metanálises e revisões sistemáticas de maior impacto e relevância científica para o tema. RESULTADOS: A análise das informações consolidou a obesidade central, diabetes melitus tipo 2, dislipidemia e hipertensão como os fatores de risco mais bem relacionados à DHGNA. Entretanto, outros fatores foram destacados, como diferenças entre gêneros, etnia, fatores genéticos e o papel da imunidade inata, como estes fatores adicionais que podem estar implicados na instalação, progressão e prognóstico da doença. CONCLUSÃO: O conhecimento dos fatores de risco para a DHGNA no contexto da síndrome metabólica amplia os caminhos para: 1) reconhecer pacientes com risco elevado para a doença; 2) elucidar vias comuns a outras comorbidades; 3) determinar fatores de risco relacionados a pior prognóstico; 4) desenvolver estratégias terapêuticas com o objetivo de reduzir fatores de risco; 4) aplicar os conhecimentos adquiridos nas políticas públicas de saúde com foco em estratégias preventivas.

Sequencing of E2 and NS5A regions of HCV genotype 3a in Brazilian patients with chronic hepatitis.

Hepatitis C virus (HCV) is a major cause of liver disease throughout the world. The NS5A and E2 proteins of HCV genotype 1 were reported to inhibit the double-stranded (ds) RNA-dependent protein kinase (PKR), which is involved in the cellular antiviral response induced by interferon (IFN). The response to IFN therapy is quite different between genotypes, with response rates among patients infected with types 2 and 3 that are two-three-fold higher than in patients infected with type 1. Interestingly, a significant percentage of HCV genotype 3-infected patients do not respond to treatment at all. The aim of this paper was to analyse the sequences of fragments of the E2 and NS5A regions from 33 outpatients infected with genotype 3a, including patients that have responded (SVR) or not responded (NR) to treatment. HCV RNA was extracted and amplified with specific primers for the NS5A and E2 regions and the PCR products were then sequenced. The sequences obtained covered amino acids (aa) 636-708 in E2 and in NS5A [including the IFN sensitivity determining region (ISDR), PKR-binding domain and extended V3 region)]. In the E2 and NS5A regions, we did observe aa changes among patients, but these changes were not statistically significant between the SVR and NR groups. In conclusion, our results suggest that the ISDR domain is not predictive of treatment success in patients infected with HCV genotype 3a.

Sequencing of E2 and NS5A regions of HCV genotype 3a in Brazilian patients with chronic hepatitis

Hepatitis C virus (HCV) is a major cause of liver disease throughout the world. The NS5A and E2 proteins of HCV genotype 1 were reported to inhibit the double-stranded (ds) RNA-dependent protein kinase (PKR), which is involved in the cellular antiviral response induced by interferon (IFN). The response to IFN therapy is quite different between genotypes, with response rates among patients infected with types 2 and 3 that are two-three-fold higher than in patients infected with type 1. Interestingly, a significant percentage of HCV genotype 3-infected patients do not respond to treatment at all. The aim of this paper was to analyse the sequences of fragments of the E2 and NS5A regions from 33 outpatients infected with genotype 3a, including patients that have responded (SVR) or not responded (NR) to treatment. HCV RNA was extracted and amplified with specific primers for the NS5A and E2 regions and the PCR products were then sequenced. The sequences obtained covered amino acids (aa) 636-708 in E2 and in NS5A [including the IFN sensitivity determining region (ISDR), PKR-binding domain and extended V3 region)]. In the E2 and NS5A regions, we did observe aa changes among patients, but these changes were not statistically significant between the SVR and NR groups. In conclusion, our results suggest that the ISDR domain is not predictive of treatment success in patients infected with HCV genotype 3a.

Síndrome de Kartagener: estudo de novos casos / Kartagener's syndrome: study of new cases

Os autores apresentam dez indivíduos afetados pela síndrome de Kartagener (bronquiectasia, dextrocardia ou situs inversus totalis e sinusopatia), pertencentes a duas famílias dos municípios de Sao José de Piranhas e Cajazeiras, na Paraíba, unidas entre si por um ancestral comum na sexta geraçao. Foi observada elevada incidência de casamentos consangüíneos (dezoito): sete entre primos em primeiro grau, dez em segundo e um em terceiro grau, sendo três de consangüinidade dupla. Sao abordados aspectos históricos, etiopatogênicos, genético-epidemiológicos e clínicos, bem como a casuística estudada, a terapêutica instituída e o seguimento obtido.