Impacto do Meld e da biópsia hepática pós-reperfusão nos resultados após transplante hepático cadavérico ortotópico
Resumo
Resumo: A evolucao dos pacientes apos transplante hepatico e complexa e caracterizar o risco para complicacoes nem sempre e facil. O MELD, um consagrado preditor de mortalidade em cirroticos, tem sido empregado com sucesso no pre-transplante. Contudo, sua utilidade no pos-transplante e menos clara. Nesse contexto, um instrumento adicional de analise e a biopsia hepatica pos-reperfusao, capaz de retratar alteracoes de importancia prognostica. Dos 377 transplantes ocorridos de 1996 a 2008 no HC-UFPR, 219 pacientes foram selecionados para estudo, sendo seus prontuarios revisados e registrados os seguintes desfechos clinicos: sobrevida em 1, 3, 6 e 12 meses, tempo de internacao, complicacoes biliares, vasculares, imunologicas e infecciosas, e disfuncao do enxerto em graus variados. Os pacientes foram categorizados de acordo com MELD-Admissional: 6-15; 16-20; 21-25; >25. As biopsias pos-reperfusao foram examinadas por um patologista sem conhecimento dos resultados. As seguintes variaveis histologicas foram avaliadas: alteracoes isquemicas, congestao, esteatose, exsudato neutrofilico, fibrose, infiltrado monomorfonuclear e necrose. Utilizou-se o teste de Qui-Quadrado para variaveis binomiais e o de Kruskal- Wallis para variaveis multinomiais. Aplicou-se o coeficiente de Spearman para correlacao das variaveis histologicas e o metodo de Kaplan-Meier para comparacao de sobrevida. Considerou-se estatisticamente significativo o valor de P.0,05. Verificou-se um aumento da mortalidade nos pacientes com MELD>25 em todos os periodos (P<0,05). A chance de sobrevida em 1 ano foi semelhante nas eras pre-MELD e pos- MELD. P ra a rejeicao, houve uma tendencia de reducao com o aumento do MELD, porem sem significancia estatistica e sem diferencas nos padroes de rejeicao. Quanto as complicacoes biliares, houve aumento significativo de estenose nos pacientes com MELD>25 (P<0,00001), mas nao de fistula. Para as complicacoes vasculares, os resultados foram menos consistentes. Com relacao as complicacoes infecciosas, o MELD>25 mostrou forte associacao com a sepse (P<0,00001) e com todas as modalidades infecciosas somadas (P=0,00003). Nao houve impacto do MELD sobre disfuncao ou falencia do enxerto e nem sobre o tempo em UTI. Contudo, o tempo de internacao hospitalar foi maior nos pacientes com MELD>25 (P=0,0215). Com respeito a biopsia, as variaveis que aumentaram a mortalidade foram: esteatose (P=0,02209), infiltrado monomorfonclear (P=0,03935) e necrose celular (P<0,00001). O exsudato neutrofilico reduziu a mortalidade (P=0,00659) e a rejeicao, havendo reducao da incidencia com o aumento do exsudato (P=0,00477). As outras variaveis nao apresentaram relacao solida com a rejeicao. As alteracoes isquemicas aumentaram a incidencia de fistula (P=0,04484), mas nao de estenose. A fibrose hepatica implicou aumento na incidencia de estenose (P<0,00001), mas nao de fistula. As outras variaveis nao apresentaram relacao solida com as complicacoes biliares. Com respeito as complicacoes vasculares, verificou-se uma forte correlacao da ongestao com a trombose portal (P<0,00001) e menor da esteatose (P=0,0015). As complicacoes infecciosas apresentaram correlacao menos clara com a biopsia. Os tempos de internacao hospitalar e em UTI nao sofreram influencia de nenhuma variavel estudada.
O nao-funcionamento primario mostrou uma associacao significativa (P<0,05) com a necrose, a esteatose e o infiltrado monomorfonuclear. Em suma, este estudo mostrou que o MELD e a biopsia pos-reperfusao sao ferramentas uteis para prever omplicacoes pos-transplante. Abstract: The outcome of the patients after liver transplant is complex and to characterize the risk for complications is not always easy. The MELD, a consecrated predictor of mortality in cirrhotic, have been used successfully in the pre-transplant. However, its utility in the post-transplant is unclear. In this context, an additional instrument of analysis is the hepatic post-reperfusion biopsy, capable of portraying alterations of prognostic importance. From the 377 transplants performed in 1996 to 2008 in the HC-UFPR, 219 patients were selected. Medical records were reviewed and the following clinical outcomes were registered: mortality in 1, 3, 6 and 12 months, hospital-stay, biliary, vascular, immunologic and infectious complications, and graft dysfunction in varied degrees. The patients were categorized by MELD strata: 6-15; 16-20; 21-25; >25. The post-reperfusion biopsies had been examined by a blinded pathologist for the outcomes. The following histological variables had been evaluated: ischemic alterations, congestion, steatosis, neutrophilic infiltration, fibrosis, monomorphonuclear infiltration and necrosis. Chi-Square test was used for qualitative and Kruskal-Wallis for quantitative variables. Spearman Ls rank coefficient was used for correlation of the histological variables and the Kaplan-Meier estimator for survival comparison. The value of P.0.05 was considered statistically significant. An increase of mortality was verified in patients with MELD> the 25 in all periods (P< 0.05). The 1-year-survival was similar in the preand post-MELD eras. For rejection, there was a trend of reduction with the increase of MELD, but with no significance or differences in rejection standards. Regarding biliary complications, there was a significant increase of strictures in the patients with MELD>25 (P< 0.00001), but not of fistula. For the vascular omplications, the results were less consistent. With regard to the infectious complications, MELD> 25 showed strong association with sepsis (P< 0.00001) and with all added infectious modalities (P=0.00003). MELD had neither impact on initial poor function or PNF nor on the CUstay. However, the hospital-stay was longer in the patients with MELD> 25 (P=0.0215). Concerning the biopsy, the variables associated with increased mortality were: esteatosis (P=0.02209), monomorphonuclear infiltration (P=0.03935) and necrosis (P<0.00001). The neutrophilic infiltration reduced mortality in this study (P=0.00659). This reduction with the increase of the neutrophilic infiltration was also observed for the rejection (P=0.00477). Other histological variables did not presented solid relation with the rejection. The ischemic alterations increased the incidence of biliary fistula (P=0.04484), but not of stenosis. Fibrosis implied increase in the incidence of stenosis (P<0.00001), but not of fistula. The other variables did not presented solid relation with the biliary complications. With regard to the vascular complications, it was verified a strong correlation between congestion and the portal thrombosis (P< 0.00001) and minor of esteatosis (P=0,0015). The infectious complications presented less clear correlation with the biopsy findings. The hospital and ICU-stay did not suffered influence from other studied variables. The primary nonfunction showed significant association (P< 0.05) with the necrosis, esteatosis and the monomorphonuclear infiltration. In short, this study demonstrated that MELD and ost-reperfusion biopsy are useful tools to foresee complications after liver transplant.
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