BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA.

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.

Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

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.

Safety and efficacy of HepaSphere 50-100 µm in the treatment of hepatocellular carcinoma.

AIM: To evaluate the effects of HepaSphere 50-100 µm (Merit Medical) as a doxorubicin carrier and embolization agent for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A prospective analysis of 18 patients recruited from a national cancer center was conducted. This analysis evaluated the efficacy and safety of HepaSphere, as expressed by the treatment response rate (measured by the modified Response Evaluation Criteria in Solid Tumors, mRECIST) and by the prevalence of treatment-related adverse events, respectively. RESULTS: The cohort was predominantly male, with a mean age of 69 years. The objective response rate (complete + partial response) was 53.3%. The variable most likely to be associated with objective response was Barcelona Clinic Liver Cancer (BCLC) staging. The most prevalent adverse events were nausea, vomiting and abdominal pain. CONCLUSION: HepaSphere chemoembolization yielded a substantial objective response rate with an acceptable toxicity profile and should be considered an option for HCC treatment.

A hiponatremia como fator preditivo da perda precoce do transplante hepático na modalidade intervivos / Hyponatremia as a predictor factor of early loss after living donor liver transplantation

INTRODUÇÃO: O transplante hepático intervivos representa alternativa para reduzir a falta de doação de órgãos. OBJETIVO: Analisar a influência da natremia como fator preditivo da perda precoce do transplante hepático nos três primeiros meses na modalidade intervivos. MÉTODO: Estudo retrospectivo, observacional e analítico de 78 doentes adultos submetidos ao transplante de fígado com doador vivo. A média etária foi 50,7±6,8 anos (18 a 65 anos) e dividiu-se os doentes transplantados em grupo I, com 62 (79,5%) pacientes com sobrevivência do enxerto superior a três meses, e grupo II com 16 (20,5%), que faleceram e/ou apresentaram falha do enxerto no prazo de até três meses após a realização do transplante hepático. Foram analisadas as seguintes variáveis: sexo, idade, etiologia da doença hepática e o nível sérico de sódio no momento do transplante. Foi considerada "perda precoce" a sobrevivência do enxerto hepático menor que três meses após a realização do transplante. Na avaliação dos fatores de risco para perda precoce do enxerto hepático foram utilizados o teste do χ2, o teste t de Student e a análise uni e multivariada. A análise de sobrevivência do enxerto foi realizada pelo modelo de Kaplan-Meier. RESULTADOS: Sexo (p=0,4) e idade (p=0,67) não apresentaram diferença significante. O nível sérico de sódio foi significantemente (p=0,01) maior no grupo I do que no grupo II. CONCLUSÃO: Os valores da natremia estão associados à maior probabilidade de sucesso no transplante hepático na modalidade intervivos.

INTRODUCTION: Living donor liver transplantation has become an appreciable and effective alternative to reduce the problem resulting from the lack of organ donation. OBJECTIVE: To analyze the influence of serum sodium as a predictor of early loss of liver transplantation in the first three months in living donor modality. METHOD: In this analytical study, 78 adults submitted to living donor liver transplantation were studied retrospectively. The mean age was 50.7±6.8 years (18 to 65 years). The transplant recipients were divided into two groups: group I consisted of 62 (79.5%) patients with graft survival longer than three months, and group II consisted of 16 (20.5%) patients who died and/or showed graft failure within three months after liver transplantation. The following variables were analyzed: gender, age, etiology of liver disease and serum sodium concentration at the time of transplantation. Liver graft survival of less than three months after transplantation was defined as "early loss". The χ2 test, Student's t-test and uni and multivariate analysis were used for the evaluation of risk factors for early graft loss. Graft survival was analyzed using the Kaplan-Meier model. RESULTS: No significant difference in gender (p=0.4) and age (p=0.67) was observed between the two groups. Serum sodium concentration was significantly (p=0.01) higher in group I than in group II. CONCLUSION: Serum sodium concentration is associated with a higher probability of graft failure after living donor liver transplantation.

Predictive factors of early graft loss in living donor liver transplantation.

CONTEXT: Living donor liver transplantation has become an alternative to reduce the lack of organ donation. OBJECTIVE: To identify factors predictive of early graft loss in the first 3 months after living donor liver transplantation. METHODS: Seventy-eight adults submitted to living donor liver transplantation were divided into group I with 62 (79.5%) patients with graft survival longer than 3 months, and group II with 16 (20.5%) patients who died and/or showed graft failure within 3 months after liver transplantation. The variables analyzed were gender, age, etiology of liver disease, Child-Pugh classification, model of end-stage liver disease (MELD score), pretransplantation serum sodium level, and graft weight-to-recipient body weight (GRBW) ratio. The GRBW ratio was categorized into < 0.8 and MELD score into >18. The chi-square test, Student t-test and uni- and multivariate analysis were used for the evaluation of risk factors for early graft loss. RESULTS: MELD score <18 (P<0.001) and serum sodium level > 135 mEq/L (P = 0.03) were higher in group II than in group I. In the multivariate analysis MELD scores > 18 (P<0.001) and GRBW ratios < 0.8 (P<0.04) were significant. CONCLUSIONS: MELD scores >18 and GRBW < 0.8 ratios are associated with higher probability of graft failure after living donor liver transplantation.

Predictive factors of early graft loss in living donor liver transplantation / Fatores preditivos da perda precoce do enxerto hepático em transplante hepático intervivos

CONTEXT: Living donor liver transplantation has become an alternative to reduce the lack of organ donation. OBJECTIVE: To identify factors predictive of early graft loss in the first 3 months after living donor liver transplantation. METHODS: Seventy-eight adults submitted to living donor liver transplantation were divided into group I with 62 (79.5%) patients with graft survival longer than 3 months, and group II with 16 (20.5%) patients who died and/or showed graft failure within 3 months after liver transplantation. The variables analyzed were gender, age, etiology of liver disease, Child-Pugh classification, model of end-stage liver disease (MELD score), pretransplantation serum sodium level, and graft weight-to-recipient body weight (GRBW) ratio. The GRBW ratio was categorized into < 0.8 and MELD score into >18. The chi-square test, Student t-test and uni- and multivariate analysis were used for the evaluation of risk factors for early graft loss. RESULTS: MELD score <18 (P<0.001) and serum sodium level > 135 mEq/L (P = 0.03) were higher in group II than in group I. In the multivariate analysis MELD scores > 18 (P<0.001) and GRBW ratios < 0.8 (P<0.04) were significant. CONCLUSIONS: MELD scores >18 and GRBW < 0.8 ratios are associated with higher probability of graft failure after living donor liver transplantation.

CONTEXTO: O transplante hepático intervivos constitui alternativa para amenizar a falta de doação de órgãos. OBJETIVO: Identificar os fatores preditivos da perda precoce do enxerto hepático nos 3 primeiros meses após transplante hepático intervivo. MÉTODOS: Setenta e oito adultos submetidos ao transplante de fígado intervivos foram divididos em grupo I com 62 (79,5%) doentes com sobrevivência do enxerto superior a 3 meses, e grupo II com 16 (20,5%) que faleceram e/ou apresentaram falha do enxerto até 3 meses após o transplante hepático. As variáveis analisadas foram: sexo, idade, origem da doença hepática, classificação de Child-Pugh, critério MELD, nível sérico de sódio pré-transplante e relação GRBW. O critério MELD foi categorizado em > 18 e a relação GRBW em < 0,8. Na avaliação dos fatores de risco para perda precoce do enxerto hepático foi utilizada a análise uni e multivariada. RESULTADOS: Critério MELD <18 (P = 0,001) e nível sérico de sódio >135 mEq/L (P = 0,03) foram maiores nos doentes do grupo II. A probabilidade de perda do enxerto no transplante hepático intervivos teve como variáveis independentes o índice MELD > 18 e a relação GRBW< 0,8. CONCLUSÃO: Os valores de MELD >18 e GRBW <0,8 estão associados com maior probabilidade de insucesso no transplante hepático intervivos.

Advanced hepatocellular carcinoma. Review of targeted molecular drugs.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world in terms of incidence, accounting for approximately 630 thousand new cases per year; in addition, HCC is the third most common cause of cancer death. Worldwide, the greatest risk factors for HCC are the infections caused by hepatitis B and C viruses, which increase the risk of developing the disease by about 20 times. The standard treatment in the early stages of the disease, such as surgical resection, local ablation and liver transplantation, are able to cure a proportion of patients, but most cases of HCC present in advanced stages, precluding the use of such treatments with curative intent. In these advanced stages, systemic treatments are commonly used. Unfortunately, chemotherapy with conventional cytotoxic agents is ineffective and does not seem to modify the natural history of disease. Treatment options for patients with advanced HCC are extremely limited, but the identification of signaling pathways, and the recognition of the role of these pathways in the pathogenesis of the disease resulted in the development of drugs directed at specific therapeutic targets. One such drug is Sorafenib, a kinase inhibitor with antiangiogenic and antiproliferative properties. In conclusion, Sorafenib has demonstrated survival benefits in patients with advanced HCC, thus representing a new standard reference for systemic treatment in these cases.

Severa hiponatremia induzida pela associação de fluoxetina, hidroclorotiazida e captopril em paciente jovem / Severe hyponatremia induced by the association of fluoxetine, hydrochlorothiazide and captopril in a young patient

Descrevemos um caso de hiponatremia grave, com um dos níveis séricos de sódio mais baixos da literatura, secundário ao uso de fluoxetina, captopril e hidroclorotiazida. Paciente do sexo feminino, 45 anos, portadora de hipertensão arterial , vinha assintomática em uso de hidroclorotiazida e captopril, quando, há um mês da internação. iniciou-se fluoxetina devido sintomas de depressão. Paciente foi internada por rebaixamento de nível de consciência, com tomografia computadorizada de crânio evidenciando edema cerebral...

We describe a case of severe hyponatremia, with some of the lowest levels of sodium in the literature, secondary to the use of fluoxetine, captropil and hydrochlorothiazide. A 45-year-old female patient suffering from arterial hypertension who was being treated with hydrochlorothiazide and captopril was asymptomatic until one month prior to hospitalization when treatment with fluoxetine was initiated due to depressive symptoms. The patient was hospitalized due to a lower level of consciousness. A CT scan of the skull revealed cerebral edema...