ABSTRACT This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the “rule of 5” for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the “rule of 4” for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH.

RESUMO Trata-se de uma revisão narrativa que visa discutir a importância dos métodos elastográficos na avaliação da hipertensão portal clinicamente significativa (HPCS) em pacientes cirróticos, onde os autores propõem um algoritmo para avaliação desses pacientes. Na doença hepática crônica avançada compensada, o objetivo é prevenir o desenvolvimento de HPCS, e naqueles já com HPCS prevenir o aparecimento de varizes gastroesofágicas (VGE) e outras complicações da hipertensão portal. Na cirrose compensada, a prevalência de VGE é de 30-40% e 10-20% são varizes com risco de sangramento, portanto o uso de métodos não invasivos dispensaria o paciente de endoscopia. A elastografia hepática é um método não invasivo, seguro e reprodutível, disponível através de várias técnicas: elastografia transitória (VCTE), onda de cisalhamento (SWE) e elastografia por ressonância magnética. O Baveno VII apresentou a “regra dos 5” para VCTE: medida da rigidez hepática (LSM) ≤15 kPa e plaquetas >150.000/mm3 excluem HPCS enquanto um LSM ≥25 kPa é altamente sugestivo de HPCS. Além disso, foi proposta a “regra dos 4” para SWE: pacientes com ≥17 kPa podem ser considerados como portadores de HPCS. Por fim, a medição da rigidez do baço (SSM) foi proposta como uma técnica mais específica para prever a presença de HPCS. Em conclusão, a elastografia ganhou prestígio na avaliação não invasiva de pacientes com doença hepática crônica avançada, ao permitir a adoção de medidas profiláticas ao sugerir a presença de HPCS.

Abstract Objective: To evaluate the degree of tumor necrosis after transarterial chemoembolization (TACE), used as a bridging therapy in patients awaiting liver transplantation, and its effect on survival. Materials and Methods: This was a retrospective cohort study involving 118 patients submitted to TACE prior to liver transplantation, after which the degree of tumor necrosis in the explant and post-transplant survival were evaluated. Results: Total necrosis of the neoplastic nodule in the explant was observed in 76 patients (64.4%). Of the patients with total necrosis in the explanted liver, 77.8% had presented a complete response on imaging examinations. Drug-eluting bead TACE (DEB-TACE), despite showing a lower rate of complications than conventional TACE, provided a lower degree of total necrosis, although there was no statistical difference between the two. By the end of the study period, 26 of the patients had died. Survival was longer among the patients with total necrosis than among those with partial or no necrosis (HR = 2.24 [95% CI: 0.91-5.53]; p = 0.078). Conclusion: In patients undergoing TACE as a bridging therapy, total tumor necrosis appears to be associated with improved patient survival.

Resumo Objetivo: Avaliar os resultados da necrose tumoral após quimioembolização transarterial (TACE) como terapia ponte e seu reflexo na sobrevida dos pacientes. Materiais e Métodos: Estudo de coorte retrospectivo, com 118 pacientes que realizaram TACE, em que foram avaliados o grau de necrose tumoral no explante e a sobrevida pós-transplante. Resultados: Necrose total do nódulo neoplásico no explante foi observada em 76 pacientes (64,4%). Observou-se que 77,8% dos pacientes com necrose total no explante hepático tinham apresentado resposta completa nos exames de imagem. A DEB-TACE, apesar de ter demonstrado menor taxa de intercorrências, proporcionou menor grau de necrose total em relação à TACE convencional, a despeito de não haver diferença estatística. Ao final do seguimento do estudo, o número de óbitos foi de 26. A sobrevida foi maior nos pacientes que tiveram necrose total quando comparada com grau de necrose parcial ou ausência de necrose [HR = 2,24 (IC 95%: 0,91-5,53); p = 0,078]. Conclusão: Necrose completa do tumor nos pacientes submetidos a TACE como terapia ponte parece estar associada com melhora da sobrevida.

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 Objetivo: Avaliar os resultados da necrose tumoral após quimioembolização transarterial (TACE) como terapia ponte e seu reflexo na sobrevida dos pacientes. Materiais e Métodos: Estudo de coorte retrospectivo, com 118 pacientes que realizaram TACE, em que foram avaliados o grau de necrose tumoral no explante e a sobrevida pós-transplante. Resultados: Necrose total do nódulo neoplásico no explante foi observada em 76 pacientes (64,4%). Observou-se que 77,8% dos pacientes com necrose total no explante hepático tinham apresentado resposta completa nos exames de imagem. A DEB-TACE, apesar de ter demonstrado menor taxa de intercorrências, proporcionou menor grau de necrose total em relação à TACE convencional, a despeito de não haver diferença estatística. Ao final do seguimento do estudo, o número de óbitos foi de 26. A sobrevida foi maior nos pacientes que tiveram necrose total quando comparada com grau de necrose parcial ou ausência de necrose [HR = 2,24 (IC 95%: 0,91-5,53); p = 0,078]. Conclusão: Necrose completa do tumor nos pacientes submetidos a TACE como terapia ponte parece estar associada com melhora da sobrevida.

Abstract Objective: To evaluate the degree of tumor necrosis after transarterial chemoembolization (TACE), used as a bridging therapy in patients awaiting liver transplantation, and its effect on survival. Materials and Methods: This was a retrospective cohort study involving 118 patients submitted to TACE prior to liver transplantation, after which the degree of tumor necrosis in the explant and post-transplant survival were evaluated. Results: Total necrosis of the neoplastic nodule in the explant was observed in 76 patients (64.4%). Of the patients with total necrosis in the explanted liver, 77.8% had presented a complete response on imaging examinations. Drug-eluting bead TACE (DEB-TACE), despite showing a lower rate of complications than conventional TACE, provided a lower degree of total necrosis, although there was no statistical difference between the two. By the end of the study period, 26 of the patients had died. Survival was longer among the patients with total necrosis than among those with partial or no necrosis (HR = 2.24 [95% CI: 0.91-5.53]; p = 0.078). Conclusion: In patients undergoing TACE as a bridging therapy, total tumor necrosis appears to be associated with improved patient survival.

ABSTRACT BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

RESUMO RACIONAL: O transplante hepático (TH) é o único tratamento a proporcionar sobrevida a longo prazo para pacientes com “acute-on-chronic liver failure” (ACLF). Vários estudos identificaram fatores prognósticos para pacientes em ACLF que não realizam TH, porém há poucos dados na literatura sobre fatores prognósticos nessa população transplantada. OBJETIVOS: Avaliar desfechos de pacientes ACLF submetidos a TH, e seus preditores de mortalidade. MÉTODOS: Foram avaliados pacientes em ACLF submetidos a TH entre janeiro de 2005 e abril de 2021. Variáveis como valores CLIF-C ACLF e pontuação no ACLF foram comparadas com os desfechos. RESULTADOS: A sobrevida de ACLF pós TH de pacientes (n=25) em 90 dias, 1, 3, 5 e 7 anos, foi de 80, 76, 59,5, 54,1 e 54,1% versus 86,3, 79,4, 72,6, 66,5 e 61,2% para pacientes submetidos a TH por outras indicações (n=344), (p=0,525). Não houve diferença estatística para mortalidade em 01 ano e 90 dias entre pacientes com os três graus de ACLF (ACLF-1 vs. ACLF-2 vs. ACLF-3), bem como quando comparados a pacientes não ACLF. O escore “chronic liver failure consortium” (CLIF-C) ACLF não se correlacionou com desfechos de óbito. Nenhuma das outras variáveis estudadas mostrou-se preditora independente de mortalidade em 90 dias, após um ano ou global. CONCLUSÕES: TH conferiu sobrevida em longo prazo à maioria dos pacientes transplantados, semelhante aos pacientes submetidos à TH por outras indicações. Nenhuma das variáveis estudadas mostrou-se fator prognóstico associado a desfechos de sobrevida pós-TH para pacientes com ACLF. Estudos adicionais são necessários para estabelecer fatores prognósticos pós-TH em pacientes com ACLF.

SUMMARY OBJECTIVE: The aim of the present study was to evaluate the outcomes of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. METHODS: A retrospective longitudinal observational study was carried out evaluating 38 cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. The outcomes were evaluated in an outpatient follow-up period of 3 months. The assumed significance level was 5%. RESULTS: The indications for transjugular intrahepatic portosystemic shunt were refractory ascites in 21 (55.3%), variceal hemorrhage in 13 (34.2%), and hydrothorax in 4 (10.5%) patients. There was development of hepatic encephalopathy in 10 (35.7%) patients after transjugular intrahepatic portosystemic shunt. From the 21 patients with refractory ascites, resolution was observed in 1 (3.1%) patient, and in 16 (50.0%) patients, there was ascites control. Regarding transjugular intrahepatic portosystemic shunt after variceal bleeding, 10 (76.9%) patients remained without new bleeding or hospitalizations in the follow-up period. The global survival in the follow-up period in patients with and without hepatic encephalopathy was 60 vs. 82%, respectively (p=0.032). CONCLUSION: Transjugular intrahepatic portosystemic shunt can be considered in decompensated cirrhotic patients; however, the development of hepatic encephalopathy which can shorten survival should be focused.

Abstract Every activity that involves exploitation of natural resources, such as fishing, needs to be organized and conducted based on information from monitoring programs to allow continuous evaluation. With the increasing fishing pressure in Brazil, the understanding of the importance of fisheries monitoring programs and how they can inform and assist in conservation decision-making remains limited. Based on the literature on fisheries and participatory conservation, we call attention to the need to generate information on the national fisheries sector in order to improve fisheries in the country. Given the context of the need to generate information on fishing stocks under exploitation, as well as to identify potential alternative fisheries and carry out various sectoral analyses in compliance with the 2030 Agenda for Sustainable Development, we present and discuss in the present paper the lack of a system of continuous fishing monitoring in Brazil and its effects on the fisheries sustainability in the country.

Resumo Toda atividade que atua envolvendo a exploração de recursos naturais, como a pesca, precisa ser organizada e conduzida com base nas informações dos programas de monitoramento para permitir uma avaliação contínua. Com o aumento da pressão pesqueira no Brasil, o entendimento da importância dos programas de monitoramento da pesca e como eles podem informar e auxiliar na tomada de decisões de conservação permanece limitado. Com base na literatura sobre pesca e conservação participativa, chamamos a atenção para a necessidade de gerar informações sobre o setor pesqueiro nacional para melhorar a pesca no país. Dado o contexto da necessidade de gerar informações sobre os estoques pesqueiros em exploração, bem como identificar potenciais alternativas de pesca e realizar diversas análises setoriais em conformidade com a Agenda 2030 para o Desenvolvimento Sustentável, é apresentada e discutida no presente trabalho a falta de um sistema de monitoramento contínuo da pesca no Brasil e seus efeitos na sustentabilidade da pesca no país.

Abstract Currently, gonadotropin products (follicle stimulating hormone, FSH, and luteinizing hormone, LH) used in animal reproduction are produced by extraction and purification from abattoir-derived pituitary glands. This method, relying on animal-derived materials, carries the potential risk of hormone contamination and pathogen transmission. Additionally, chorionic gonadotropins are extracted from the blood of pregnant mares (equine chorionic gonadotropin; eCG) or the urine of pregnant women (human chorionic gonadotropin; hCG). However, recent advancements have introduced recombinant gonadotropins for assisted animal reproduction therapies. The traditional use of FSH for superovulation has limitations, including labor requirements and variability in superovulation response, affecting the success of in vivo (SOV) and in vitro (OPU/IVEP) embryo production. FSH treatment for superstimulation before OPU can promote the growth of a homogenous follicular population and the recovery of competent oocytes suitable for IVEP procedures. At present, a single injection of a preparation of long-acting bovine recombinant FSH (rFSH) produced similar superovulation responses resulting in the production of good-quality in vivo and in vitro embryos. Furthermore, the treatment with eCG at FTAI protocol has demonstrated its efficacy in promoting follicular growth, ovulation, and P/AI, mainly in heifers and anestrous cows. Currently, treatment with recombinant glycoproteins with eCG-like activity (r-eCG) have shown promising results in increasing follicular growth, ovulation, and P/AI in cows submitted to P4/E2 -based protocols. Bovine somatotropin (bST) is a naturally occurring hormone found in cows. Recombinant bovine somatotropin (rbST), produced through genetic engineering techniques, has shown potential in enhancing reproductive outcomes in ruminants. Treatment with rbST has been found to improve P/IA, increase donor embryo production, and enhance P/ET in recipients. The use of recombinant hormones allows to produce non-animal-derived products, offering several advantages in assisted reproductive technologies for ruminants. This advancement opens up new possibilities for improving reproductive efficiency and success rates in the field of animal reproduction.

Abstract Methane emission from beef and dairy cattle combined contributes around 4.5-5.0% of total anthropogenic global methane. In addition to enteric methane (CH4) produced by the rumen, cattle production also contributes carbon dioxide (CO2) (feed), nitrous oxide (N2O) (feed production, manure) and other CH4 (manure) to the total greenhouse gas (GHG) budget of beef and dairy production systems. The relative contribution in standard dairy systems is typically enteric CH4 58%, feed 29% and manure 10%. Herds with low production efficiency can have an enteric CH4 contribution up to 90%. Digestibility of feed can impact CH4 emission intensity. Low fertility herds also have a greater enteric CH4 contribution. Animals with good feed conversion efficiency have a lower emission intensity of CH4/kg of meat or milk. Feed efficient heifers tend to be lean and have delayed puberty. Fertility is a major driver of profit in both beef and dairy cattle, and it is highly important to apply multi-trait selection when shifting herds towards improved efficiency and reduced CH4. Single nucleotide polymorphisms (SNPs) have been identified for feed efficiency in cattle and are used in genomic selection. SNPs can be utilized in artificial insemination and embryo transfer to increase the proportion of cattle that have the attributes of efficiency, fertility and reduced enteric CH4. Prepubertal heifers genomically selected for favourable traits can have oocytes recovered to produce IVF embryos. Reproductive technology is predicted to be increasingly adopted to reduce generation interval and accelerate the rate of genetic gain for efficiency, fertility and low CH4 in cattle. The relatively high contribution of cattle to anthropogenic global methane has focussed attention on strategies to reduce enteric CH4 without compromising efficiency and fertility. Assisted reproductive technology has an important role in achieving the goal of multiplying and distributing cattle that have good efficiency, fertility and low CH4.

SUMMARY OBJECTIVE: This study aimed to evaluate the correlation between Nonalcoholic fatty liver disease and cardiac abnormalities. METHODS: Patients with Nonalcoholic fatty liver disease who attended an outpatient clinic in Southern Brazil were prospectively evaluated. Patients should be older than 18 years and have steatosis. RESULTS: A total of 174 patients were evaluated. The mean age was 63±12 years, 65% were women, 71% white, 82.2% hypertensive, 52.3% diabetic, 56.3% obese, and 30% dyslipidemic. There was no association between Nonalcoholic fatty liver disease and cardiac abnormalities, even after adjusting for age, sex, and metabolic syndrome. CONCLUSIONS: The present study did not show a direct correlation between Nonalcoholic fatty liver disease and cardiac abnormalities, regardless of metabolic syndrome.

SUMMARY OBJECTIVE: Nonalcoholic fatty liver disease is the most prevalent cause of chronic liver disease worldwide. Nonalcoholic steatohepatitis is associated with increased mortality rates due to the liver and cardiovascular diseases. The gold standard for discriminating nonalcoholic fatty liver disease activity and staging is the anatomopathological examination, which is an invasive method. In this regard, noninvasive methods, such as scintigraphy, have been under investigation. This study investigated the role of scintigraphy in the diagnosis of nonalcoholic steatohepatitis in obese patients with nonalcoholic fatty liver disease undergoing bariatric surgery. METHODS: Patients undergoing bariatric surgery and liver biopsy were prospectively included. 99mTc-phytate scintigraphy was performed to assess liver/spleen, spleen/heart, and liver/heart uptake ratios, while 99mTc-isonitrile scintigraphy assessed liver/heart ratio. To evaluate the presence of nonalcoholic steatohepatitis, the results of 99mTc-phytate scintigraphy and 99mTc-isonitrile scintigraphy were compared with the anatomopathological examination. RESULTS: Sixty-one patients with nonalcoholic fatty liver disease were allocated into two groups, namely, nonalcoholic steatohepatitis (n=49) and non-nonalcoholic steatohepatitis (n=12). The results of scintigraphic images obtained after the infusion of radiopharmaceutical 99mTc-phytate in liver/spleen, spleen/heart, liver/heart ratios and 99mTc-isonitrile liver/heart ratio presented no difference between groups with and without nonalcoholic steatohepatitis with an accuracy of 47.5, 37.7, 50.8, and 52.5%, respectively. CONCLUSION: Scintigraphy was not proven to be a useful method to differentiate patients with and without nonalcoholic steatohepatitis.

RESUMO CONTEXTO: A doença hepática gordurosa não-alcoólica (DHGNA) é a doença hepática mais prevalente no mundo. Nos Estados Unidos, a DHGNA já é a segunda causa de transplante hepático. O espectro da doença abrange desde a esteatose simples, que apresenta curso benigno, até esteato-hepatite não-alcoólica (EHNA), que pode progredir para cirrose e suas complicações. O desenvolvimento de métodos não invasivos para o diagnóstico e estadiamento da EHNA e da fibrose hepática visa diminuir a necessidade de biópsia hepática, um procedimento invasivo e não raro associado a complicações. OBJETIVO: Analisar o desempenho do índice triglicerídeo-glicose (TyG Index) para o diagnóstico e estadiamento da DHGNA em pacientes obesos. MÉTODOS: Este é um estudo transversal retrospectivo. Foram analisados todos os prontuários de pacientes candidatos a cirurgia bariátrica em um hospital de referência do Sul do Brasil e calculado o TyG Index, um escore composto por dois exames laboratoriais (triglicerídeos e glicose de jejum), realizados previamente à cirurgia. O desempenho do TyG Index em relação aos achados anatomopatológicos hepáticos foi avaliado, e calculada a curva ROC para avaliação de esteatose simples, EHNA e fibrose hepática. O NAFLD Fibrosis Score (NFS) também foi avaliado. RESULTADOS: Foram avaliados 423 pacientes. O melhor ponto de corte do TyG Index para a exclusão de esteatose simples significativa (grau 2-3) foi de 8,76, com sensibilidade 67,6%, especificidade 65,1%, valor preditivo positivo (VPP) 46,3%, valor preditivo negativo (VPN) 81,8%, acurácia 65,8% e AUROC 0,66 (P=0,005). Na avaliação de EHNA significativa (grau 2-3), o melhor ponto de corte foi de 8,82 com sensibilidade 57,3%, especificidade 58,6%, VPP 33,7%, VPN 78,8%, acurácia 58,8% e AUROC 0,58 (P=0,022). Em relação à fibrose avançada (grau 3-4), o melhor ponto de corte do TyG Index foi de 8,91 com sensibilidade 61,8%, especificidade 62,5%, VPP 13,8%, VPN 94,4%, acurácia 62,4% e AUROC 0,69 (P<0,001). Ao analisarmos o desempenho do NFS no diagnóstico de fibrose avançada, o ponto de corte de <-1,455 excluiu fibrose avançada com sensibilidade 59,4%, especificidade 51%, VPP 11%, VPN 92,4% e acurácia 51,7%. Entretanto, o ponto de corte de 0,676 para fibrose avançada apresentou sensibilidade de 21,9%, especificidade 83%, VPP 11,7%, VPN 91,2% e acurácia 77,3%. A AUROC foi de 0,54 (P=0,480). CONCLUSÃO: O TyG Index não apresentou bom desempenho para o diagnóstico e estadiamento da esteatose simples e da EHNA. Entretanto, foi capaz de excluir fibrose avançada em pacientes obesos candidatos a cirurgia bariátrica.

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its prevalence is increasing alongside obesity. In United States, NAFLD is already the second leading cause of liver transplantation. The spectrum of the disease ranges from simple steatosis, which has a benign course, to steatohepatitis, which may progress to cirrhosis and its complications. The rising of noninvasive methods for diagnosing and staging non-alcoholic steatohepatitis (NASH) and fibrosis decreases the need of liver biopsy, as well as the costs and the occurrence of complications related to it. OBJECTIVE: To analyze the performance of the triglyceride-glucose index to evaluate steatosis, NASH and liver fibrosis in obese patients with NAFLD. METHODS: This is a retrospective cross-sectional study. Every medical record of patients who were candidates for bariatric surgery at a leading hospital in Southern Brazil were analyzed. The triglyceride-glucose index (TyG Index), a method composed only of two simple laboratory tests (serum triglycerides and fasting glucose levels), was performed prior to surgery. The TyG Index performance regarding the anatomopathological findings was evaluated, and the AUROC curve was calculated to evaluate the best cut-off point for diagnosing steatosis, non-alcoholic steatohepatitis and liver fibrosis grade. Also, the NAFLD fibrosis Score (NFS) was evaluated. RESULTS: A total of 423 patients were evaluated. The TyG Index with a cut-off point of 8.76 excluded significant simple steatosis (grade 2-3) in obese patients, with 67.6% sensitivity, 65.1% specificity, 46.3% positive predictive value (PPV), 81.8% negative predictive value (NPV), 65.8% accuracy and 0.66 AUROC (P=0.005). In the evaluation of NASH, the TyG Index with a cut-off point of 8.82 excluded significant NASH (grade 2-3) with 57.3% sensitivity, 58.6% specificity, 33.7% PPV, 78.8% NPV, 58.2% accuracy and 0.58 AUROC (P=0.022). When evaluating liver fibrosis, the TyG Index with a cut-off point of 8.91 showed a sensitivity of 61.8%, a specificity of 62.5%, a PPV of 13.8 and a NPV of 94.4% for exclusion of advanced fibrosis (F3-4), with a 62.4% accuracy and 0.69 AUROC (P<0.001). When analyzing the performance of NFS in the diagnosis of advanced fibrosis, the cut-off point <-1.455 excluded advanced fibrosis with sensitivity of 59.4%, specificity of 51%, PPV of 11%, NPV of 92.4% and accuracy of 51.7%. However, the cut-off point of 0.676 to diagnose advanced fibrosis presented sensitivity of 21.9%, specificity of 83%, PPV of 11.7%, NPV of 91.2% and 77.3% accuracy. The AUROC was 0.54 (P=0.480). CONCLUSION: TyG Index did not perform well in the diagnosis of significant steatosis and NASH. However, it was able to exclude advanced fibrosis in obese patients who are candidates for bariatric surgery.

RESUMO Neste trabalho introduzimos os conceitos de coloração total absolutamente equilibrada e composição de grafos. Provamos que para n , K ∈ ℕ, se k + 1 | n, existe um grafo k-regular conexo com n vértices que admite uma coloração total absolutamente equilibrada com no máximo Δ + 2 cores. Esse resultado mostra que existe uma relação entre a regularidade e o número de vértices do grafo que possibilita a construção de uma família de grafos regulares, denominados grafos harmônicos. Em seguida, mostramos que todo grafo harmônico de grau k pode ser obtido como composição sucessiva de grafos completos de grau k. Finalizamos, provando que os grafos harmônicos não possuem vértice de corte, fato que implica que todo grafo desta família possui conectividade de vértices κ G ≥ 2.

ABSTRACT In this work we introduce the concepts of absolute equitable total coloring and graph composition. We prove that for n , K ∈ ℕ, if k + 1 | n, there is a connected k regular graph with n vertices that admits a absolute equitable total coloring, with at most Delta + 2 colors. This result shows that there is a relationship between regularity and the number of vertices of the graph that makes it possible to build a family of regular graphs, called harmonic graphs. Then, we show that every harmonic graph of degree k can be obtained as successive composition of complete graphs of degree k. We conclude by proving that the harmonic graphs do not have a cut vertex, that implies that every graph of this family has vertex connectivity κ G ≥ 2.

RESUMO CONTEXTO: O carcinoma hepatocelular (CHC) é o câncer primário do fígado mais frequente e a cirrose é considerada uma doença pré-maligna. Nesse contexto, a sequência evolutiva do nódulo displásico de baixo grau e nódulo displásico de alto grau (NDAG) para CHC precoce e CHC avançado tem sido estudada. O diagnóstico diferencial entre NDAG e CHC precoce ainda é um desafio, principalmente em biópsias por agulha. OBJETIVO: Avaliar um painel de imunohistoquímica para diferenciar nódulos displásicos de CHC. MÉTODOS: Foram incluídos pacientes com cirrose submetidos à ressecção cirúrgica ou transplante de fígado. A sensibilidade, especificidade e acurácia para o diagnóstico da neoplasia foram analisadas avaliando cinco marcadores: proteína de choque térmico 70kDa, glipican 3, glutamina sintetase, clatrina de cadeia pesada e beta-catenina. P≤0,05 foi considerado estatisticamente significativo. RESULTADOS: Cento e cinquenta e seis nódulos foram incluídos; destes, 57 eram CHC, 14 NDAG, 18 nódulos displásicos de baixo grau e 67 macronódulos regenerativos. A sensibilidade do diagnóstico de CHC foi de 64,9% para glipican 3 e 77,2% para glutamina sintetase, enquanto a especificidade foi de 96,0% e 96,0%, respectivamente. Quando o painel de quatro marcadores foi considerado (excluindo beta catenina), a especificidade variou de 87,9% para um marcador positivo a 100% para pelo menos três marcadores. A melhor acurácia para o diagnóstico de CHC foi obtida com pelo menos dois marcadores positivos, o que foi associado a uma sensibilidade de 82,5% e especificidade de 99%. CONCLUSÃO: O diagnóstico diferencial de nódulos displásicos e CHC por critérios morfológicos pode ser desafiador. Imunomarcadores são úteis e devem ser usados para o diagnóstico diferencial entre CHC e NDAG.

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

Resumo Fundamento Na prática clínica, há evidências de falhas na prescrição de terapias baseadas em evidências para pacientes de alto risco cardiovascular. Entretanto, no Brasil, ainda são insuficientes os dados sobre a evolução ao longo de 1 ano desses pacientes. Objetivos Descrição no acompanhamento de 12 meses da utilização de terapias baseadas em evidência e da ocorrência de desfechos cardiovasculares maiores e seus principais preditores em um registro brasileiro multicêntrico de pacientes de alto risco cardiovascular. Métodos Estudo observacional prospectivo que documentou a prática clínica ambulatorial de indivíduos acima de 45 anos e de alto risco cardiovascular tanto em prevenção primária como secundária. Os pacientes foram seguidos por 1 ano e avaliou-se a prescrição de terapias baseadas em evidência e a ocorrência de eventos cardiovasculares maiores (infarto agudo do miocárdio [IAM], acidente vascular cerebral [AVC], parada cardíaca e mortalidade por causa cardiovascular). Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados De julho de 2010 até agosto de 2014, 5.076 indivíduos foram incluídos em 48 centros, sendo 91% dos 4.975 pacientes elegíveis acompanhados em centros de cardiologia e 68,6% em prevenção secundária. Em 1 ano, o uso concomitante de antiplaquetários, estatinas e inibidores da enzima conversora de angiotensina (IECA) reduziu de 28,3% para 24,2% (valor de p < 0,001). A taxa de eventos cardiovasculares maiores foi de 5,46%, e os preditores identificados foram: idade, pacientes em prevenção secundária e nefropatia diabética. Conclusões Neste grande registro nacional de pacientes de alto risco cardiovascular, foram identificados preditores de risco semelhantes aos registros internacionais, porém a adesão da prescrição médica a terapias baseadas em evidência esteve abaixo dos dados da literatura internacional e apresentou piora significativa em 1 ano. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background In clinical practice, there is evidence of failure to prescribe evidence-based therapies for patients at high cardiovascular risk. However, in Brazil, data on 1-year outcomes of these patients remain insufficient. Objectives To describe the use of evidence-based therapies and the occurrence of major cardiovascular outcomes and their major predictors in a 12-month follow-up of a Brazilian multicenter registry of patients at high cardiovascular risk. Methods This prospective observational study documented the outpatient clinical practice of managing patients over 45 years of age and of high cardiovascular risk in both primary and secondary prevention. Patients were followed-up for 1 year, and the prescription of evidence-based therapies and the occurrence of major cardiovascular events (myocardial infarction, stroke, cardiac arrest, and cardiovascular death) were assessed. P-values < 0.05 were considered statistically significant. Results From July 2010 to August 2014, a total of 5076 individuals were enrolled in 48 centers, 91% of the 4975 eligible patients were followed-up in cardiology centers, and 68.6% were in secondary prevention. At 1 year, the concomitant use of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors reduced from 28.3% to 24.2% (p < 0.001). Major cardiovascular event rate was 5.46%, and the identified predictors were age, patients in secondary prevention, and diabetic nephropathy. Conclusions In this large national registry of patients at high cardiovascular risk, risk predictors similar to those of international registries were identified, but medical prescription adherence to evidence-based therapies was inferior and significantly worsened at 1 year. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)