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.

Acute abdomen in intensive care unit: etiology, comorbidity and severity of 1,523 patients / Abdome agudo em unidade de terapia intensiva: etiologia, comorbidades e severidade de 1.523 pacientes

ABSTRACT BACKGROUND: Clinical features and outcomes of patients admitted to the intensive care unit due to acute abdomen are important to be investigated. AIMS: To evaluate the outcomes of critically ill subjects with acute abdomen according to etiology, comorbidity and severity. METHODS: Outcomes of 1,523 patients (878 women, mean age 66±18 years) consecutively admitted to a specialized gastrointestinal intensive care unit with different causes of acute abdomen from January 2012 to December 2019, were retrospectively evaluated according to etiology, comorbidity and severity. RESULTS: The most common causes of acute abdomen were obstructive and inflammatory, particularly large bowel obstruction (27%), small bowel obstruction (18%) and acute pancreatitis (17%). Overall mortality was 13%. Surgery was required in 34% of patients. Median length of stay in the hospital was 9 [1-101] days. On univariate analysis mortality was significantly associated with age, APACHE II, Charlson comorbidity index, requirement for surgery and malignancy (p<0.0001), but only APACHE II, Charlson comorbidity index and surgical interventional remained significant on multivariate analysis. CONCLUSIONS: Critically ill patients admitted to the intensive care unit with acute abdomen constitute a heterogeneous group of subjects with different prognosis. Mortality is more related to the severity of the disease, comorbidity and need for surgery than to the etiology of the acute abdomen.

RESUMO RACIONAL: As características clínicas e os desfechos dos pacientes internados na unidade de terapia intensiva devido ao abdômen agudo são importantes serem investigados. OBJETIVOS: Avaliar os desfechos de indivíduos gravemente doentes com abdômen agudo de acordo com etiologia, gravidade e comorbidade. MÉTODOS: Os desfechos de 1.523 pacientes (878 mulheres, média de idade 66±18 anos) que foram previamente admitidos em uma unidade de terapia intensiva especializada em doenças gastrointestinais, com diferentes causas de abdômen agudo entre janeiro de 2012 e dezembro de 2019, foram avaliados retrospectivamente segundo etiologia, comorbidade e gravidade. RESULTADOS: As causas mais comuns de abdômen agudo foram obstrutivas e inflamatórias, com destaque para obstrução em colon (27%), em intestino delgado (18%) e pancreatite aguda (17%). A mortalidade geral foi de 13%. A cirurgia foi necessária em 34%. A média de permanência no hospital foi de 9 [1-101] dias. Na análise univariada a mortalidade foi significativamente associada à idade, APACHE II, índice de comorbidade de Charlson, necessidade de abordagem cirúrgica e presença de malignidade (p<0,0001), mas apenas APACHE II, índice de comorbidade de Charlson e intervenção cirúrgica permaneceram significativos na análise multivariada. CONCLUSÕES: Pacientes internados na unidade de terapia intensiva com abdômen agudo constituem um grupo heterogêneo de indivíduos com prognóstico diferente. A mortalidade está mais relacionada com a gravidade da doença, comorbidade e necessidade de cirurgia do que com a etiologia do abdome agudo.

Frequência e gravidade do envolvimento hepático em transtornos hipertensivos da gravidez / Frequency and severity of liver involvement in hypertensive disorders of pregnancy

ABSTRACT Background: Pre-eclampsia (PE) and eclampsia (E) are among the leading causes of maternal and fetal morbidity and mortality. Both are associated with an evolving spectrum of liver disorders. Objective: The aim of this study was to evaluate the frequency and severity of liver involvement in pregnant women admitted to an intensive care unit with PE/E and to assess its influence on adverse maternal and fetal outcomes. Methods: All subjects, hospitalized between January 2012 and March 2019, were retrospectively evaluated for clinical and biochemical liver-related abnormalities and their frequencies were subsequently correlated with maternal-fetal outcomes. Results: A total of 210 women (mean age 31±6.4 years, mean gestational age 33.8±4.1 weeks) with PE/E were included in the study. Most of them had severe hypertension (n=184) and symptoms of abdominal pain (48%) and headache (40%). Liver enzymes abnormalities were seen in 49% of the subjects, usually less than five times the upper limit of normal. Subcapsular hemorrhage and spontaneous hepatic rupture were identified in one woman who died. No patient had definitive diagnosis for acute fatty liver of pregnancy, neither acute liver failure. A total of 62% of deliveries occurred before 37 weeks. Fetal mortality was observed in 6 (3%) cases. There was no correlation between mean levels of liver enzymes and maternal and fetal outcomes. Conclusion: Biochemical abnormalities of liver enzymes are frequently seen in women with PE/E, but outside the spectrum of HELLP syndrome, they are not associated with adverse maternal and fetal outcomes. Liver-related complications are rare but can be life-threatening.

RESUMO Contexto Pré-eclâmpsia (PE) e eclâmpsia (E) estão entre as principais causas de morbimortalidade materna e fetal. Ambas estão associadas a comprometimento hepático com diferentes formas de evolução. Objetivo O objetivo deste estudo foi avaliar a frequência e a gravidade do envolvimento hepático em gestantes internadas em uma unidade de terapia intensiva (UTI) com PE/E e avaliar sua influência em desfechos maternos e fetais adversos. Métodos: Pacientes hospitalizados entre janeiro 2012 e março 2019 com PE/E foram avaliados retrospectivamente quanto às anormalidades clínicas e bioquímicas relacionadas ao fígado e suas frequências foram posteriormente correlacionadas com os resultados materno-fetais. Resultados: Um total de 210 mulheres (idade média 31±6,4 anos, idade gestacional média 33,8±4,1 semanas) com PE/E foram incluídas no estudo. A maioria delas apresentava hipertensão grave (n=184), sintomas de dor abdominal (48%) e cefaleia (40%). Anormalidades das enzimas hepáticas foram observadas em 49% dos indivíduos, geralmente menos de cinco vezes o limite superior do normal. Hemorragia subcapsular e ruptura hepática espontânea foram identificadas em uma mulher que faleceu. Nenhuma paciente teve diagnóstico definitivo de esteatose hepática aguda da gravidez, nem insuficiência hepática aguda grave. Um total de 62% dos partos ocorreu antes de 37 semanas. A mortalidade fetal foi observada em 6 (3%) casos. Não houve correlação entre os níveis médios de enzimas hepáticas e os resultados maternos e fetais. Conclusão Anormalidades bioquímicas hepáticas são frequentemente vistas em mulheres com PE/E, mas fora do contexto da síndrome HELLP, não estão associadas a resultados maternos e fetais adversos. As complicações relacionadas ao fígado são raras, mas podem ser fatais.

Análise das infecções relacionadas aos cuidados de saúde e hospitalares nos pacientes cirróticos críticos / Analysis of healthcare associated and hospital acquired infections in critically ill patients with cirrhosis

ABSTRACT Background Bacterial infections occur in 43—59% of cirrhotic patients admitted to the intensive care unit with impact in morbidity and mortality. An increase in the frequency of multidrug-resistant (MDRO) and extensively drug-resistant (XDRO) organisms has been described in bacterial infections in cirrhotic patients with an adverse impact on survival. Objective To characterize community-acquired (CA), healthcare-associated (HCA), and hospital-acquired (HA) infections in cirrhotic patients and their impact in the occurrence of adverse outcomes. Methods This study included all cirrhotic patients admitted in an intensive care unit specialized in liver and gastrointestinal diseases in Brazil between January 2012 and June 2018. Frequency and topography of infections were retrospectively evaluated, as well as the frequency of MDRO and XDRO organisms, and their impact in occurrence of acute kidney injury, hepatorenal syndrome, acute-on-chronic liver failure, sepsis and mortality. Results A total of 374 infections were observed and classified as CA (22%), HCA (34%) and hospital-acquired (44%). Eighty-nine (54%) episodes of hospital-acquired infections were second infections. Spontaneous bacterial peritonitis (32%) and urinary tract infection (23%) were the most common infections. Culture-proven infections were positive in 61% of the cases, mainly gram-negative bacteria (73%). Acute kidney injury, hepatorenal syndrome and sepsis were observed, respectively, in 48%, 15% and 53% of the cases. MDRO and XDRO were seen, respectively, in 35% and 16%, mainly in HCA (48% vs 26% in CA infections, P=0.02) and hospital-acquired (58% vs 26% in CA infections, P=0.0009). Adverse outcomes were more frequently observed in subjects with hospital-acquired infections when compared to HCA and CA infections. Hospital-acquired, HCA and second infections were independently associated with in-hospital mortality. Conclusion Hospital-acquired, HCA and second infections are increasingly associated with either MDRO and/or XDRO and are independent predictors of in-hospital mortality. Their recognition and proper selection of appropriate empiric antibiotic regimens are important measures to reduce in-hospital mortality.

RESUMO Contexto As infecções bacterianas ocorrem em 43—59% dos pacientes cirróticos internados em unidade de terapia intensiva com impacto na morbimortalidade. Um aumento na frequência de bactérias multirresistentes e com resistência estendida foi descrito em infecções bacterianas em pacientes cirróticos, com um impacto adverso na sobrevida. Objetivo Caracterizar as infecções adquiridas na comunidade, relacionadas aos cuidados de saúde (RCS) e hospitalares em pacientes cirróticos e seu impacto na ocorrência de desfechos adversos. Métodos Este estudo incluiu todos os pacientes cirróticos internados em uma unidade de terapia intensiva especializada em doenças hepáticas e gastrointestinais no Brasil entre janeiro de 2012 e junho de 2018. A frequência e topografia das infecções foram avaliadas retrospectivamente, bem como a frequência de bactérias multirresistentes e resistência estendida, e seu impacto na ocorrência de lesão renal aguda, síndrome hepatorrenal, insuficiência hepática crônica agudizada, sepse e mortalidade. Resultados Um total de 374 infecções foram observadas e classificadas como infecções adquiridas na comunidade (22%), RCS (34%) e infecções hospitalares (44%). Oitenta e nove (54%) episódios de infecções hospitalares foram identificadas como segunda infecção. Peritonite bacteriana espontânea (32%) e infecção do trato urinário (23%) foram as infecções mais comuns. As infecções comprovadas por cultura foram positivas em 61% dos casos, principalmente ocasionadas por bactérias gram-negativas (73%). Lesão renal aguda, síndrome hepatorrenal e sepse foram observados respectivamente, em 48%, 15% e 53% dos casos. Bactérias multirresistentes e resistência estendida foram observadas respectivamente, em 35% e 16%, principalmente nos RCS (48% vs 26% em infecções adquiridas na comunidade, P=0,02) e infecções hospitalares (58% vs 26% em infecções adquiridas na comunidade, P=0,0009). Os resultados adversos foram observados com mais frequência em indivíduos com infecções nosocomiais em comparação com infecções relacionadas aos cuidados de saúde e comunitárias. Infecções hospitalares, RCS e ocorrência de uma segunda infecção foram independentemente associadas à mortalidade intra-hospitalar. Conclusão Infecções hospitalares, relacionadas aos cuidados de saúde e reinfecções estão cada vez mais associadas a bactérias multirresistentes e/ou resistência estendida e são preditores independentes de mortalidade intra-hospitalar. Seu reconhecimento e seleção adequada de regimes antibióticos empíricos apropriados são medidas importantes para reduzir a mortalidade intra-hospitalar.

Brazilian registry for the elimination of hepatitis C in dialysis units: a call to action for Nephrology / Registro brasileiro para eliminação da hepatite C nas unidades de diálise: um chamado para a Nefrologia

Abstract Infection by the hepatitis C virus is more prevalent in patients on dialysis than in the general population in Brazil, and has been associated with worse outcomes. Current therapy for hepatitis C is highly effective, safe, and widely available in Brazil, with coverage provided to dialysis patients with chronic kidney disease, which makes the elimination of hepatitis C a viable target. The Brazilian Society of Nephrology, the Brazilian Society of Hepatology, and the Brazilian Liver Institute developed the "Brazilian Registry for the Elimination of Hepatitis C in Dialysis Units". This project aims to identify, treat, and monitor the response to treatment of patients on chronic dialysis infected with the hepatitis C virus in Brazil. This article presents the issue and invites Brazilian nephrologists to rally around the achievement of a significant goal.

Resumo A infecção pelo vírus da hepatite C é mais prevalente em pacientes em diálise do que na população geral no Brasil e implica um pior prognóstico. O tratamento atual para hepatite C é altamente eficaz, seguro e disponível no país, inclusive para a população de pacientes crônicos em diálise, o que torna a eliminação do vírus da hepatite C uma meta viável. A Sociedade Brasileira de Nefrologia, a Sociedade Brasileira de Hepatologia e o Instituto Brasileiro do Fígado desenvolveram o "Registro Brasileiro para Eliminação da Hepatite C nas Unidades de Diálise". O projeto visa identificar pacientes em diálise crônica com vírus da hepatite C no Brasil, além de tratar e monitorar a resposta virológica após o tratamento. Este breve artigo apresenta o problema e convida os nefrologistas brasileiros a unirem forças nesse objetivo comum.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

ABSTRACT Background and aims: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methods: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. Results: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. Conclusion: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Perception of Brazilian medical students toward organ donation

SUMMARY OBJECTIVE: Brazil ranks second in gross numbers of kidney and liver transplantations, but deceased organ donation is still far below the national demand for organs. Apart from a high family refusal rate, another significant barrier is healthcare workers' inappropriate knowledge concerning organ donation and transplantation. Since most of them have recently graduated from university, this study aimed to evaluate the awareness and attitudes of medical students concerning organ donation. METHODS: Between August and September 2021, a web-based survey with 10 overlapping questions was sent to medical students from several Brazilian universities after advertisements on social media. RESULTS: A total of 391 (60% female, mean age: 23 [17-41] years) students answered the survey. Most of them (91%) would like to donate organs in case of death, and 75% have already notified their family. The main reasons for not becoming a donor were fear of body manipulation (n=3) or family reaction (n=2) and religious reasons (n=2). When inquired, 54% were unaware of brain death criteria, and half of them claimed to have never discussed the topic in medical classes. Except for Glasgow coma scale (97%), pupillary (72%), and corneal (53%) reflexes, less than 25% knew other reflexes required for brain death diagnosis. CONCLUSION: Most medical students declared themselves as organ donors, and most informed their families. However, many students have never learned about crucial steps toward organ donation, which may impact their adequate recognition of potential organ donors later in life.

Leukocyte ratios are useful early predictors for adverse outcomes of COVID-19 infection

ABSTRACT Leukocyte biomarkers, including the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte-(MLR), platelet-to-lymphocyte (PLR) ratios and systemic immune-inflammation index (SII) have been associated with severity and mortality of patients with COVID-19. The purpose of this study was to evaluate the association of baseline leukocyte biomarkers calculated in the emergency department (ED) with the disease severity and mortality. This was a retrospective cohort study that evaluated 1,535 (mean age 57+18 years) patients with SARS-CoV-2 infection in the ED of a single reference center. Outcomes were severity, defined as intensive care unit (ICU) admission requirement, and in-hospital mortality. All leukocyte biomarkers were calculated in the ED before the hospital admission. Their ability to predict the severity and mortality was measured using receiver operating characteristic (ROC) curves. Severity and mortality were observed in 30.9% and 12.6% of the patients, respectively, and were significantly correlated with NLR, MLR, PLR and SII, but only NLR was independently associated with both outcomes on multivariate analysis. Analysis of ROC curves revealed that NLR (0.78 for severity and 0.80 for mortality) and SII (0.77 for severity and 0.75 for mortality) had the best ability to predict mortality, when compared to other ratios. The highest AUC was observed for NLR, employing cut-off points of 5.4 for severity and 5.5 for mortality. Leukocyte biomarkers, particularly NLR, are capable of predicting the severity and mortality of patients with SARS-CoV-2 infection and could be important adjunct tools to identify patients in the ED that are more prone to develop adverse outcomes.

Microbiota intestinal, prebióticos, probióticos e simbióticos em doenças gastrointestinais e hepáticas: procedimentos de reunião conjunta da Sociedade Brasileira de Hepatologia (SBH), Núcleo Brasileiro de Estudos do Helicobacter pylori e Microbiota (NBEHPM) e Federação Brasileira de Gastroenterologia (FBG) / Gut microbiota, prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases: proceedings of a joint meeting of the brazilian society of hepatology (sbh), brazilian nucleus for the study of helicobacter pylori and microbiota (nbehpm), and brazilian federation of gastroenterology (fbg)

ABSTRACT Over the last years, there is growing evidence that microorganisms are involved in the maintenance of our health and are related to various diseases, both intestinal and extraintestinal. Changes in the gut microbiota appears to be a key element in the pathogenesis of hepatic and gastrointestinal disorders, including non-alcoholic fatty liver disease, alcoholic liver disease, liver cirrhosis, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile - associated diarrhea. In 2019, the Brazilian Society of Hepatology (SBH) in cooperation with the Brazilian Nucleus for the Study of Helicobacter Pylori and Microbiota (NBEHPM), and Brazilian Federation of Gastroenterology (FBG) sponsored a joint meeting on gut microbiota and the use of prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to provide practical information about this topic, addressing the latest discoveries and indicating areas for future studies.

RESUMO Nos últimos anos, um volume crescente de evidências indica que os microrganismos estão envolvidos na manutenção da saúde humana e também estão relacionados a várias doenças, tanto intestinais quanto extraintestinais. Alterações na microbiota intestinal parecem ser um elemento chave na patogênese de doenças hepáticas e gastrointestinais, incluindo doença hepática gordurosa não-alcoólica, doença hepática alcoólica, cirrose hepática, doenças inflamatórias intestinais, síndrome do intestino irritável e diarreia associada ao Clostridium difficile. Em 2019, a Sociedade Brasileira de Hepatologia (SBH) em colaboração com o Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM) e a Federação Brasileira de Gastroenterologia (FBG) realizaram um encontro exclusivamente voltado para a discussão sobre microbiota e uso de prebióticos, probióticos e simbióticos em doenças hepáticas e gastrointestinais. Este texto resume os principais pontos discutidos durante o evento, e tem a intenção de fornecer informações práticas sobre o assunto, abordando as descobertas mais recentes e indicando áreas para estudos futuros.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil / Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil

RESUMO Objetivo: Definir o perfil epidemiológico e os principais determinantes de morbimortalidade dos pacientes cirúrgicos não cardíacos de alto risco no Brasil. Métodos: Estudo prospectivo, observacional e multicêntrico. Todos os pacientes cirúrgicos não cardíacos admitidos nas unidades de terapia intensiva, ou seja, considerados de alto risco, no período de 1 mês, foram avaliados e acompanhados diariamente por, no máximo, 7 dias na unidade de terapia intensiva, para determinação de complicações. As taxas de mortalidade em 28 dias de pós-operatório, na unidade de terapia intensiva e hospitalar foram avaliadas. Resultados: Participaram 29 unidades de terapia intensiva onde foram realizadas cirurgias em 25.500 pacientes, dos quais 904 (3,5%) de alto risco (intervalo de confiança de 95% - IC95% 3,3% - 3,8%), tendo sido incluídos no estudo. Dos pacientes envolvidos, 48,3% eram de unidades de terapia intensiva privadas e 51,7% de públicas. O tempo de internação na unidade de terapia intensiva foi de 2,0 (1,0 - 4,0) dias e hospitalar de 9,5 (5,4 - 18,6) dias. As taxas de complicações foram 29,9% (IC95% 26,4 - 33,7) e mortalidade em 28 dias pós-cirurgia 9,6% (IC95% 7,4 - 12,1). Os fatores independentes de risco para complicações foram Simplified Acute Physiology Score 3 (SAPS 3; razão de chance − RC = 1,02; IC95% 1,01 - 1,03) e Sequential Organ Failure Assessment Score (SOFA) da admissão na unidade de terapia intensiva (RC =1,17; IC95% 1,09 - 1,25), tempo de cirurgia (RC = 1,001; IC95% 1,000 - 1,002) e cirurgias de emergências (RC = 1,93; IC95% 1,10 - 3,38). Em adição, foram associados com mortalidade em 28 dias idade (RC = 1,032; IC95% 1,011 - 1,052) SAPS 3 (RC = 1,041; IC95% 1,107 - 1,279), SOFA (RC = 1,175; IC95% 1,069 - 1,292) e cirurgias emergenciais (RC = 2,509; IC95% 1,040 - 6,051). Conclusão: Pacientes com escores prognósticos mais elevados, idosos, tempo cirúrgico e cirurgias emergenciais estiveram fortemente associados a maior mortalidade em 28 dias e mais complicações durante permanência em unidade de terapia intensiva.

ABSTRACT Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

Atualização das recomendações da Sociedade Brasileira de Hepatologia para o diagnóstico e tratamento do carcinoma hepatocellular / Brazilian society of hepatology updated recommendations for diagnosis and treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

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 2015 suas primeiras recomendações sobre a abordagem do CHC. Desde então, novas evidências sobre o diagnóstico e tratamento do CHC foram relatadas na literatura médica, levando a diretoria da SBH a promover uma reunião monotemática sobre câncer primário de fígado em agosto de 2018 com o intuito de atualizar as recomendações sobre o manejo da neoplasia. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização baseada em evidências científicas visando que pudesse nortear a prática clínica multidisciplinar do CHC. O texto resultante foi submetido a avaliação e aprovação de todos membros da SBH através de sua homepage. O documento atual é a versão final que contêm as recomendações atualizadas e revisadas da SBH.

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

RESUMO Para definir as recomendações baseadas em evidências científicas sobre o diagnóstico e tratamento das doenças autoimnus do fígado, a Sociedade Brasileira de Hepatologia organizou em Outubro de 2014, encontro monotemático em São Paulo. Um Comitê organizador de sete investigadores foi selecionado pela Diretoria da Sociedade para organizar a agenda científica, assim como para selecionar vinte debatedores para fazer uma revisão sistemática e apresentar tópicos relacionados à hepatite autoimune, colangite esclerosante primária, cirrose biliar primária e suas síndromes de superposição (overlap). O texto inicial do submetidoo a apreciação e aprovação da Sociedade Brasileira de Hepatologia através de consulta a todos associados através da home page da Sociedade, O trabalho apresentado representa a versão final do trabalho original, devidamente revisado e organizado em tópicos, segundo as recomendações da Sociedade Brasileira de Hepatologia.

Intensive care management of patients with liver disease: proceedings of a single-topic conference sponsored by the Brazilian Society of Hepatology

ABSTRACT Survival rates of critically ill patients with liver disease has sharply increased in recent years due to several improvements in the management of decompensated cirrhosis and acute liver failure. This is ascribed to the incorporation of evidence-based strategies from clinical trials aiming to reduce mortality. In order to discuss the cutting-edge evidence regarding critical care of patients with liver disease, a joint single topic conference was recently sponsored by the Brazilian Society of Hepatology in cooperation with the Brazilian Society of Intensive Care Medicine and the Brazilian Association for Organ Transplantation. This paper summarizes the proceedings of the aforementioned meeting and it is intended to guide intensive care physicians, gastroenterologists and hepatologists in the care management of patients with liver disease.

RESUMO A sobrevida de pacientes cirróticos críticos aumentou significantemente nos últimos anos devido a inúmeros avanços obtidos no manejo do paciente com cirrose descompensada e com insuficiência hepática aguda grave, particularmente após a incorporação na prática clínica de uma série de estratégias baseadas em evidencias com impacto reconhecido na redução de mortalidade. Com o intuito de discutir as principais evidencias disponíveis na literatura médica sobre o assunto, a Sociedade Brasileira de Hepatologia, em conjunto com a Associação de Medicina Intensiva Brasileira e a Associação Brasileira de Transplantes de Órgãos promoveu uma reunião monotemática sobre o manejo do paciente hepatopata crítico, que ocorreu em 21 de maio de 2014 na cidade do Rio de Janeiro. O relatório da reunião foi resumido no presente manuscrito com o objetivo de nortear a prática clínica de intensivistas, gastroenterologistas e hepatologistas no manejo do paciente hepatopata em ambiente de terapia intensiva.

Encefalopatia hepática: relatório da 1ª reunião monotemática da Sociedade Brasileira de Hepatologia / Hepatic encephalopathy: report 1st monothematic meeting of the Brazilian Society

A encefalopatia hepática (EH) é um distúrbio funcional do sistema nervoso central (SNC) associado à insufi ciência hepática, de fisiopatologia multifatorial e complexa. Devido aos avanços no conhecimento sobre o manejo da EH na cirrose e na insuficiência hepática aguda (IHA), a diretoria da Sociedade Brasileira de Hepatologia (SBH) promoveu uma reunião monotemática acerca da fi siopatologia, diagnóstico e tratamento da EH, abordando aspectos controversos relacionados ao tema. Com a utilização de sistemática da medicina baseada em evidências, foram abordados o manejo da EH e da hipertensão intracraniana na IHA, o manejo da EH episódica na cirrose, as controvérsias no manejo da EH e a abordagem da EH mínima. O objetivo desta revisão é resumir os principais tópicos discutidos na reunião monotemática e apresentar recomendações sobre o manejo da síndrome votadas pelo painel de expertos da SBH.

Hepatic encephalopathy (HE) is a functional disorder of the central nervous system (CNS) associated with liver failure, either end-stage chronic liver disease or fulminant hepatic failure. Its pathogenesis remains complex and poorly understood. In view of recent advances in the management of HE, the Brazilian Society of Hepatology endorsed a monothematic meetingregarding HE in order to gather experts in the to discuss related data and to draw evidence-based recommendations concerning: management of HE and intracranial hypertension in FHF, treatment of episodic HE in cirrhosis, controversies in the management of EH including difficult to treat cases and diagnostic and treatment challenges for minimal HE. The purpose of this review is to summarize the lectures and recommendations made by the panel of experts of the Brazilian Society of Hepatology.

Reunião com expertos em hepatotoxicidade da Sociedade Brasileira de Hepatologia: analgésicos, antitérmicos, insumos vegetais, fitoterápicos, homeopáticos e AINEs / Meeting with Society's Hepatotoxic Experts Brazilian Institute of Hepatology: Analgesics, Antipyretics, Vegetable, Phytotherapic, Homeopathic and AINS

No dia 05 de agosto de 2010, no Hotel Blue Tree, no bairro do Morumbi em São Paulo, a Sociedade Brasileira de Hepatologia realizou uma reunião de expertos para discutir alguns assuntos importantes referentes à toxicidade hepática. Esta reunião foi de responsabilidade exclusiva da Sociedade Brasileira de Hepatologia (SBH), sem interferência de agências ou da indústria farmacêutica. Dentre os assuntos discutidos, três deles mereceram destaque pelo volume de solicitações de esclarecimentos encaminhadas diretamente à Sociedade Brasileira de Hepatologia. O site da SBH recebe com frequência tais solicitações de outras sociedades ou diretamente de colegas, assim como do público não-médico, por questões pertinentes a estes assuntos: 1. papel do acetaminofen/paracetamol nas alterações hepáticas da dengue; 2. eficácia e segurança da medicina alternativa (homeopatia, medicina natural, fitoterápicos); 3. alterações hepáticas induzidas por analgésicos, antitérmicos e anti-inflamatórios não-esteroides com foco no seu uso na dengue.Dentro deste contexto, a Sociedade Brasileira de Hepatologia organizou uma sessão durante todo o dia 05 de agosto para discutir unicamente estes temas.

Variceal bleeding: consensus meeting report from the Brazilian Society of Hepatology / Hemorragia digestiva alta varicosa: relatório do 1º Consenso da Sociedade Brasileira de Hepatologia

In the last decades, several improvements in the management of variceal bleeding have resulted in a significant decrease in morbidity and mortality of patients with cirrhosis and bleeding varices. Progress in the multidisciplinary approach to these patients has led to a better management of this disease by critical care physicians, hepatologists, gastroenterologists, endoscopists, radiologists and surgeons. In this respect, the Brazilian Society of Hepatology has, recently, sponsored a consensus meeting in order to draw evidence-based recommendations on the management of these difficult-to-treat subjects. An organizing committee comprised of four people was elected by the Governing Board and was responsible to invite 27 researchers from distinct regions of the country to make a systematic review of the subject and to present topics related to variceal bleeding, including prevention, diagnosis, management and treatment, according to evidence-based medicine. After the meeting, all participants met together for discussion of the topics and the elaboration of the aforementioned recommendations. The organizing committee was responsible for writing the final document. The meeting was held at Salvador, May 6th, 2009 and the present manuscript is the summary of the systematic review that was presented during the meeting, organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

Vários avanços científicos obtidos nas últimas duas décadas foram incorporados no manejo da hemorragia digestiva alta varicosa, levando a uma redução significante da sua morbimortalidade, atribuída à abordagem multidisciplinar do sangramento varicoso por paramédicos, emergencistas, intensivistas, gastroenterologistas, hepatologistas, endoscopistas, radiologistas intervencionistas e cirurgiões. Recentemente, a Sociedade Brasileira de Hepatologia patrocinou uma reunião de consenso, visando o estabelecimento de recomendações nacionais, sobre o manejo da hemorragia digestiva alta varicosa, incluindo sua prevenção, diagnóstico e tratamento, de acordo com a melhor evidência científica disponível. A diretoria da Sociedade Brasileira de Hepatologia elegeu quatro membros para a comissão organizadora que, por sua vez, convidou 27 pesquisadores de diferentes regiões do país, para realizar uma revisão sistemática sobre tópicos relacionados ao manejo hemorragia digestiva alta varicosa. A reunião de consenso ocorreu em Salvador, BA, em 6 de março de 2009. Após o encontro, todos os participantes se reuniram para elaboração das recomendações, cuja redação ficou sob a responsabilidade da comissão organizadora. O presente artigo descreve as recomendações da Sociedade Brasileira de Hepatologia sobre o manejo do sangramento associado à hipertensão portal, divididas em módulos e precedidas por resumo das apresentações realizadas na reunião de consenso.

Poor outcomes with treatment of hepatorenal syndrome type 1 with splancnic vasoconstrictors and albumin: report of seven cases and review of the literature / Resultados adversos com o emprego de vasoconstritores esplâncnicos e albumina para tratamento da síndrome hepatorrenal do tipo 1: relato de sete casos e revisão da literatura

CONTEXT: Treatment of hepatorenal syndrome type 1 (HRS-1) with splancnic vasoconstrictors and high-dose albumin has been associated with reversal of renal failure in approximately 60 percent to 80 percent of the cases in pilot or uncontrolled studies. OBJECTIVE: To evaluate the results of treatment of HRS-1 with terlipressin and high-dose albumin. METHODS: All patients with HRS-1 that underwent treatment with terlipressin and high-dose albumin at our unit were retrospectively reviewed. Outcomes including reversal of renal failure and death were recorded and compared to baseline clinical and laboratory parameters. RESULTS: Seven subjects (median age 64 [47-69] years, 5 males) with median Child-Pugh and MELD scores of 12 [10-15] and 22 [17-38], respectively, hospitalized with decompensated chronic liver disease secondary to tense ascitis and infections, who exhibited criteria for HRS-1, were submitted to therapy with terlipressin and high-dose albumin according to a predefined standard protocol. Baseline creatinine levels were 2.9 [2.3-4.0] mg/mL. None of the patients achieved reversal of HRS-1 and five subjects died on-treatment due to sudden-death (n = 1), multiple organ dysfunction associated with end-stage liver failure (n = 2) and sepsis (n = 2). CONCLUSIONS: Treatment of HRS-1 with terlipressin and high-dose albumin was not associated with reversal of renal failure, but most of the treated subjects had severe end-stage liver disease with high MELD scores as well as high baseline creatinine values, parameters previously associated with bad outcomes.

CONTEXTO: O tratamento da síndrome hepatorrenal do tipo 1 (SHR-1) com vasoconstritores esplâncnicos e albumina intravenosa tem se associado, em relatos de caso e estudos piloto não-controlados, à reversão da insuficiência renal em 60 por cento-80 por cento dos pacientes tratados. OBJETIVO: Avaliar os resultados do tratamento da SHR-1 com terlipressina e albumina. MÉTODOS: Foram avaliados, retrospectivamente, todos os pacientes hospitalizados com o diagnóstico de SHR-1 que se submeteram a tratamento com terlipressina associada à albumina em altas doses. As frequências de reversão de insuficiência renal e óbito foram comparados com parâmetros clínicos e laboratoriais pré-tratamento. RESULTADOS: Sete pacientes (5 homens, idade mediana 64 [47-69] anos) com mediana de pontuação Child-Pugh e MELD respectivamente de 12 [10-15] e 22 [17-38], admitidos na unidade de terapia intensiva por desconforto respiratório secundário à ascite tensa ou por infecções, que apresentaram critérios para SHR-1 e eligibilidade para o transplante de fígado foram submetidos a tratamento com terlipressina e albumina, de acordo com protocolo pré-definido. Níveis de creatinina prévios ao tratamento foram de 2.9 [2.3-4.0] mg/mL. Nenhum paciente apresentou reversão da SHR-1 e cinco faleceram por morte súbita (n = 1), disfunção de múltiplos órgãos associada a falência hepática (n = 2) e sepse (n = 2), a maioria antes de completar o tratamento. CONCLUSÕES: O tratamento da SHR-1 com terlipressina e albumina, em altas doses, não foi associado à reversão da insuficiência renal em nenhum dos pacientes tratados, mas a maioria dos pacientes apresentava doença hepática em fase avançada, com altos valores de MELD, e níveis elevados de creatinina pré-tratamento, parâmetros previamente associados com pior resposta e prognóstico mais reservado.

Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis

BACKGROUND: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). AIMS: To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our cohort, nine (47 percent) patients were homozygous for the C282Y mutation, two (11 percent) were heterozygous for the H63D mutation, and one each (5 percent) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. CONCLUSIONS: One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.