RESUMO
Yellow fever (YF) is a viral hemorrhagic fever that typically involves the liver. Brazil recently experienced its largest recorded YF outbreak, and the disease was fatal in more than a third of affected individuals, mostly because of acute liver failure. Affected individuals are generally treated only supportively, but during the recent Brazilian outbreak, selected patients were treated with liver transplant. We took advantage of this clinical experience to better characterize the clinical and pathological features of YF-induced liver failure and to examine the mechanism of hepatocellular injury in YF, to identify targets that would be amenable to therapeutic intervention in preventing progression to liver failure and death. Patients with YF liver failure rapidly developed massive transaminase elevations, with jaundice, coagulopathy, thrombocytopenia, and usually hepatic encephalopathy, along with pathological findings that included microvesicular steatosis and lytic necrosis. Hepatocytes began to express the type 3 isoform of the inositol trisphosphate receptor (ITPR3), an intracellular calcium (Ca2+) channel that is not normally expressed in hepatocytes. Experiments in an animal model, isolated hepatocytes, and liver-derived cell lines showed that this new expression of ITPR3 was associated with increased nuclear Ca2+ signaling and hepatocyte proliferation, and reduced steatosis and cell death induced by the YF virus. Conclusion: Yellow fever often induces liver failure characterized by massive hepatocellular damage plus steatosis. New expression of ITPR3 also occurs in YF-infected hepatocytes, which may represent an endogenous protective mechanism that could suggest approaches to treat affected individuals before they progress to liver failure, thereby decreasing the mortality of this disease in a way that does not rely on the costly and limited resource of liver transplantation.
RESUMO
Fundamento: O transplante hepático (TH) é cirurgia de grande porte indicada para tratamento de portadores de cirrose avançada e está associado a diversos riscos. Por esta razão, faz-se necessário estratificar o risco no período pré- transplante através da avaliação da função miocárdica e pesquisa de doença coronariana. Objetivo: Demonstrar a aplicabilidade da ressonância miocárdica cardíaca (RMC) na avaliação morfofuncional cardíaca, bem como seu uso na avaliação da isquemia miocárdica no pré-transplante. Método: Realizou-se estudo retrospectivo e descritivo, sendo avaliados dados de pacientes cirróticos encaminhados ao ambulatório de TH no período de Janeiro/2014 a Julho/2016 que se submeteram a RMC para avaliação cardíaca e como teste provocativo de isquemia miocárdica. Resultados: Foram encaminhados 135 pacientes; destes, 39 realizaram RMC. A idade média foi de 60 anos (50 a 71). Cerca de 87% (n = 34) eram do sexo masculino. Prevaleceu etiologia etanólica 56% (n = 22). A maioria era de pacientes CHILD C, MELD ≥ 18, (n = 26). A RMC evidenciou isquemia miocárdica em 03 pacientes (7,6%). A cineangiocoronariografia foi realizada nestes pacientes e a presença de doença arterial coronariana grave (obstrução > 70%) foi confirmada em todos, com consequente revascularização miocárdica. Em um seguimento de até 2 anos e 7 meses, a sobrevida dos transplantados foi de 87%, sem intercorrências cardiológicas. Conclusões: A realização da RMC na avaliação de cirróticos no pré-transplante mostrou-se estratégia segura ao evidenciar a presença de alterações morfofuncionais da cardiomiopatia do cirrótico e a presença de isquemia miocárdica. Entretanto, novos estudos devem ser realizados para padronização de métodos e critérios para avaliação cardiovascular em cirróticos
Background: Liver transplantation (LT) is a huge surgery performed to treat patients with advanced liver cirrhosis and is associated with several risks. For this reason, is necessary to stratify the risk in the pre-transplantation period through the evaluation of myocardial function and ischemia Objective: To demonstrate the applicability of cardiac magnetic resonance (CMR) in cardiac morphologic and functional evaluation, as well use in the evaluation of myocardial ischemia in pre-transplantation. Methods: Retrospective, descriptive study. Data from patients with cirrhosis referred to the liver transplant outpatient clinic from January 2014 to July 2016 were analyzed they underwent CMR for cardiac evaluation and as provocative test of myocardial ischemia. Results: 135 patients were referred of these, 39 performed CMR. The mean age was 60 (50 to 71). About 87% (n = 34) were males. Alcoholic etiology prevailed 56% (n = 22). Most were of CHILD C patients with MELD ≥ 18, (n = 26). CMR showed myocardial ischemia in 03 patients (7,6%). Coronary angiography was performed and presence of severe coronary artery disease (obstruction > 70%) was confirmed, with consequent myocardial revascularization. At a follow-up of 2 years and 7 months, the survival of transplanted patients was 87%, without cardiologic complications. Conclusions: The realization of CMR in the evaluation of cirrhotic patients in the pre-transplantation proved to be a safe strategy by showing presence of morphologic and functional changes of the cirrhotic cardiomyopathy and the presence of myocardial ischemia. However, more studies should be performed to standardize methods and criteria for cardiovascular evaluation in cirrhotic patients before the liver transplantation
