RESUMO
INTRODUCTION AND OBJECTIVES: The Choosing Wisely (CW) initiative aims to improve daily practice supported by evidence concerning unnecessary medical tests, procedures, and treatments. This philosophy is essential in managing viral hepatitis (VH), which primary care physicians increasingly carry out. It is also essential to achieving disease elimination. Thus, the aim of our study was to propose evidence-based CW recommendations in VH. MATERIALS AND METHODS: The Brazilian Society of Hepatology (SBH) formed a panel of experts in VH who selected evidence-based CW recommendations, which were subsequently scrutinized and ranked by all members of SBH using a web-based approach. RESULTS: Five recommendations were chosen in order of importance: 1) do not order anti-HCV testing after achieving sustained virological response; 2) do not request serial HCV viral load to evaluate HCV progression, 3) do not add ribavirin to direct-acting antivirals in non-cirrhotic, naïve HCV patients; 4) do not screen for hepatocellular carcinoma in HCV patients with none to moderate fibrosis (≤ F2); 5) do not request anti-HBs after HBV vaccination, except for children born to HBV-infected mothers, hemodialysis patients, healthcare professionals, people who have had sexual contact with chronic HBV carriers, HIV-positive persons and immunocompromised individuals (hematopoietic stem-cell transplant recipients or persons receiving chemotherapy). CONCLUSIONS: CW recommendations may help general practitioners adopt a more rational and cost-effective approach in managing patients with VH in Brazil and Latin America, leading to lesser waste or harm to patients.
Assuntos
Gastroenterologia , Hepatite C Crônica , Hepatite Viral Humana , Neoplasias Hepáticas , Criança , Humanos , Antivirais/efeitos adversos , Brasil , América Latina , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite Viral Humana/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Cirrose Hepática/patologia , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Idoso , Brasil , Carbamatos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Pirrolidinas , Fatores Sexuais , Resposta Viral Sustentada , Valina/análogos & derivadosRESUMO
Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.
Assuntos
Anemia/induzido quimicamente , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Pirofosfatases/genética , Ribavirina/uso terapêutico , Anemia/genética , Antivirais/efeitos adversos , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Hepatite C Crônica/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Ribavirina/efeitos adversos , Inosina TrifosfataseRESUMO
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
Assuntos
Carcinoma Hepatocelular , Gastroenterologia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Brasil , Sociedades MédicasRESUMO
Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been associated with a sustained virological response (SVR) in interferon-ribavirin (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European and African populations. In this study, the genotype frequency of two IL28B SNPs (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in Brazil was evaluated and the SNP sufficient to predict the treatment response outcome was determined. A total of 66 naïve genotype-1 chronic HCV-infected patients were genotyped and the associated viral kinetics and SVR were assessed. The overall SVR was 38%. Both the viral kinetics and SVR were associated with rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However, rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG = 18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860, successfully predicts SVR in the IFN-RBV treatment of HCV.
Assuntos
Hepatite C Crônica/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único/genética , Antivirais/uso terapêutico , Brasil , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Interferons , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , RNA Viral/genética , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Resultado do Tratamento , Carga ViralRESUMO
Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.
Assuntos
DNA Viral/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Cirrose Hepática/virologia , Adolescente , Adulto , Idoso , Alanina Transaminase/análise , Brasil , Criança , Estudos Transversais , Feminino , Fibrose , Genótipo , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Hepatitis C virus (HCV) is a global public health problem. Second-generation direct-acting antivirals targeting non-structural regions on the viral genome are the cornerstone for treatment of chronic infection. However, resistance-associated variants (RAVs) have been reported to be associated with therapeutic failure. The aim of this study was to assess the frequency of variants, including RAVs, in the NS3, NS5A and NS5B regions at baseline in Brazilian patients with chronic hepatitis C with HCV genotypes 1a, 1b and 3a. METHODS: Serum samples from 13 patients were used to obtain viral RNA. Massively parallel sequencing was performed using genotype-specific amplicons and a panel of Ampliseq technology for all genotypes. RESULTS: Several non-synonymous substitutions were detected at baseline for 11 responders and pre-/post-treatment for two non-responders. HCV genotype 3a was found to have significantly more non-synonymous substitutions than HCV genotype 1 in the NS3 and NS5A regions. Analyses were conducted using quantitative and qualitative inter- and intrapatient comparisons. Variants that confer resistance to the treatment used by the patients were found in both responders and non-responders. CONCLUSIONS: A wide frequency distribution of RAVs was found at baseline, and this did not interfere with the achievement of a sustained response. Evaluation of the presence of RAVs requires additional study in order to determine clinical relevance.
Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/farmacologia , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Infecção Persistente , Proteínas não Estruturais Virais/genéticaRESUMO
The association of a bariatric operation during liver transplantation may benefit patients with liver failure and obesity and sleeve gastrectomy emerges as the procedure of choice. The aim of this study is to present our experience with combined liver transplantation and sleeve gastrectomy. During an 18-month period, seven patients were submitted to simultaneous liver transplant and sleeve gastrectomy (LTSG). There were four male and three female, and the mean recipient age was 60.5 years, mean BMI was 38.2 kg/m2, and mean MELD score was 25 points. The indication for liver transplantation was nonalcoholic steatohepatitis (NASH) with hepatocellular carcinoma (HCC) in four cases, hepatitis C with HCC in one case, pure NASH in one case and alcoholic cirrhosis with HCC in one case. Six patients are alive with normal allograft function. There were no biliary complications.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Brasil , Carcinoma Hepatocelular/cirurgia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Portomesenteric vein thrombosis (PMVT) is a potentially severe complication that can occur after bariatric surgery. PMVT has gained importance because of the increasing number of bariatric surgeries being performed. to report a rare and severe complication after bariatric surgery, which is difficult to manage. To try to identify common characteristics among the cases and discuss potential causes comparing our data to the available literature. METHODS: We describe six cases of PMVT in young women with different presentations. RESULTS: All six cases occurred in young women 29-41 years old with obesity - body mass index - BMI: 36-39) and weighing 105-121 kg. The patients had few comorbidities (all of which were related to metabolic syndrome) and moderate hepatic steatosis with no sign of cirrhosis. Five patients used oral contraceptives until a few days before the operation. One patient tested positive for thrombophilia. Five patients underwent a laparoscopic sleeve gastrectomy and one underwent a gastric bypass with no complications during the operation (median operating time: 61.3 min, range 52-91 min). The mean duration of follow-up after hospitalization was 12.3 months (range: 7-18 months) and to-date only one patient has had no recanalization. CONCLUSION: The frequency of PMVT appears to be increased in woman and after sleeve gastrectomy. Our findings indicate that patients with abdominal pain weeks after bariatric surgery must be investigated.
OBJETIVO: A trombose portomesentérica (TPM) é uma complicação potencialmente grave que pode ocorrer após a cirurgia bariátrica. A TPM ganhou importância devido ao crescente número de cirurgias bariátricas sendo realizadas. Relatar complicação rara após cirurgia bariátrica, porém grave e de difícil manejo. Tentar identificar algumas características comuns aos pacientes e discutir possíveis causas, comparando a pouca literatura disponível. MÉTODOS: Descrevemos seis casos de TPM em mulheres jovens com diferentes apresentações. RESULTADOS: Todos os seis casos ocorreram em mulheres jovens de 29 a 41 anos sem obesidade grave - índice de massa corporal - IMC: 36 a 39 e com peso que variou de 105 a 121 kg. As pacientes apresentavam poucas comorbidades (todas relacionadas à síndrome metabólica) e esteatose hepática moderada, sem sinais de cirrose. Cinco pacientes usavam contraceptivos orais até dias antes da cirurgia. Uma paciente apresentou resultado positivo para trombofilia. Cinco pacientes foram submetidas a gastrectomia vertical e apenas uma submetida ao bypass gástrico sem complicações durante a cirurgia (tempo médio de operação: 61,3 min, variando de 52 a 91 min). A duração média do seguimento após a hospitalização foi de 12,3 meses (variação: 7 a 18 meses) e até o momento apenas uma paciente não teve recanalização. CONCLUSÃO: A frequência da TPM parece ser maior em mulheres e após gastrectomia vertical. Nossos achados indicam que pacientes com dor abdominal semanas após a cirurgia bariátrica devem ser investigados.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Veias Mesentéricas/diagnóstico por imagem , Trombose Venosa/etiologia , Adulto , Feminino , Humanos , Masculino , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Trombose Venosa/diagnóstico por imagemRESUMO
AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBD patients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%).
Assuntos
Hepatite B/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Estudos Transversais , DNA Viral/sangue , Diagnóstico Precoce , Feminino , Hepatite B/diagnóstico , Hepatite B/etiologia , Hepatite B/transmissão , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Genotype 1 of hepatitis C virus (HCV) is the most prevalent worldwide. Pegylated-interferon and ribavirin therapy is still used in the developing world but has less efficiency in this genotype. Single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 (IL28B) and rs1800896, rs1800871, and rs1800872 (IL10) are related to treatment outcome, but previous studies clustered nonresponse and relapse patients. The aim of this study is to analyze the frequency of those SNPs in HCV genotype 1 for response, nonresponse, or relapse. Patients were classified according to treatment outcome. Genomic DNA was extracted by blood samples and SNPs were defined by PCR and sequencing. Data analysis was performed with R project. The frequency of rs12979860 CC was similar among responders (0.48) and relapsers (0.46) and lower among nonresponders (0.18). The same trend was observed for rs8099917 TT. rs12979860 CC showed a protective effect for relapsers compared to nonresponders (OR = 0.25) as it occurs with responders (OR = 0.17). Haplotypes 12979860/C rs8099917/T were associated with protection against the nonresponder phenotype compared to responders (OR = 0.27) or relapsers (OR = 0.37). Frequency of rs12979860 and rs8099917 is different between relapsers and nonresponders, but similar between relapsers and responders.
Assuntos
Hepacivirus/patogenicidade , Hepatite C Crônica/genética , Interleucina-10/genética , Interleucinas/genética , Adulto , Antivirais/administração & dosagem , Quimioterapia Combinada , Feminino , Genótipo , Haplótipos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/genética , Interferons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Recidiva , Carga Viral/genéticaRESUMO
ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.
RESUMO
BACKGROUND: Portal hypertension in patients with liver cirrhosis causes manifestations such as esophageal varices, ascites and edema. Some studies have been conducted about the role of esophageal varices in the development of esophageal motor disorders and abnormal gastroesophageal reflux in these patients. Ascites could be a factor promoting gastroesophageal reflux and it has been questioned whether reflux would favor the rupture of varices. However there are a few studies using ambulatory esophageal pH recording in the evaluation of these patients. AIMS: Evaluate gastroesophageal reflux by pH recording in cirrhotic patients with esophageal varices and possible predictors. METHODS: Fifty one patients (28 men, 23 women, mean age of 54 years) with liver cirrhosis, diagnosed by clinical, laboratorial, image and histological findings were prospectively evaluated. All patients had esophageal varices confirmed by endoscopy and were submitted to a questionnaire about typical gastroesophageal reflux disease symptoms (heartburn and or acid regurgitation). pH recording was performed with the probe placed 5 cm above the superior lower esophageal sphincter limit, as determined by manometry. Abnormal reflux (% total time with pH < 4 >4.5%) was related to the size of varices, congestive gastropathy, ascites, severity of cirrhosis and typical gastroesophageal reflux disease symptoms. RESULTS: The caliber of the varices was considered to be small in 30 patients (59%), medium in 17 (33%) and large in 4 (8%), 21 (41%) congestive gastropathy. Ascites was observed in 17 (33%), 32 patients (63%) were classified as Child-Pugh A, 17 (33%) Child-Pugh B and 2 (4%) Child-Pugh C. Twenty seven patients (53%) presented with typical gastroesophageal reflux disease symptoms. Abnormal reflux at pH recording was found in 19 patients (37%). One of them presented with erosive esophagitis at endoscopy. There was no relation between ascites, variceal size, congestive gastropathy and Child-Pugh score and abnormal reflux. There was a correlation between typical gastroesophageal reflux disease symptoms and abnormal reflux. CONCLUSION: Abnormal gastroesophageal reflux was found in 37% of the patients with hepatic cirrhosis and esophageal varices. Only typical gastroesophageal reflux disease symptoms predicted these findings.
Assuntos
Varizes Esofágicas e Gástricas/complicações , Refluxo Gastroesofágico/etiologia , Cirrose Hepática/complicações , Adolescente , Adulto , Idoso , Varizes Esofágicas e Gástricas/cirurgia , Feminino , Refluxo Gastroesofágico/diagnóstico , Humanos , Concentração de Íons de Hidrogênio , Masculino , Manometria , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
AIM: To evaluate the performance of FibroMeterVirus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC). METHODS: First generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C. RESULTS: Seven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeterVirus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3). CONCLUSION: The stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.
RESUMO
OBJECTIVE:: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS:: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS:: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION:: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.
Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/administração & dosagem , Idoso , Brasil , Estudos Transversais , Feminino , Genótipo , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Prolina/administração & dosagem , Prolina/análogos & derivados , RNA Viral/genética , Proteínas Recombinantes/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The hepatic cirrhosis has as one of the main morbid-mortality causes, the portal hypertension with the development of esophageal varices, the possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It is important to identify causal predictive or aggravating factors and if possible to prevent them. In the last years, it has been observed the association of esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients with esophageal varices. AIMS: To study the prevalence of the esophageal motility disorders and among them, the ineffective esophageal motility, in patients with hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic and the predictive factors. METHODS: Prospectively, it has been evaluate 74 patients suffering from liver cirrhosis and esophagic varices, without previous endoscopic treatment. All of them were submitted to a clinical protocol, esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry. RESULTS: Esophageal motility disorders have been found in 44 patients (60%). The most prevalent was the ineffective esophageal motility, observed in 28%. The abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients. There were no correlation between the manometrical abnormality in general and the ineffective esophageal motility in particular and the esophageal or gastroesophageal reflux disease symptoms, the abnormal reflux, the disease seriousness, the ascites presence and the gauge of the varices. CONCLUSIONS: The majority of cirrhotic patients with non-treated esophageal varices present esophageal motor disorders. No predictive factor was found. The clinical relevance of these findings need more researches in the scope to define the real meaning of theses abnormalities.
Assuntos
Transtornos da Motilidade Esofágica/etiologia , Varizes Esofágicas e Gástricas/complicações , Cirrose Hepática/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Motilidade Esofágica/diagnóstico , Esofagoscopia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Manometria , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents.
RESUMO
BACKGROUND: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective. METHODS: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2). RESULTS: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n=325,900) and decompensated (n=45,000) cirrhosis; hepatocellular carcinoma (n=19,100); and liver-related deaths (n=16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively. CONCLUSIONS: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.