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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
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.
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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.
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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
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.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Brasil , Carcinoma Hepatocelular/cirurgia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
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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
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.
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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
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
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Humanos , Masculino , Feminino , Hepatite C/tratamento farmacológico , Terapia Antirretroviral de Alta AtividadeRESUMO
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.
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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
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.
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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
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.