Imaging techniques and histology in the evaluation of liver fibrosis in hepatosplenic schistosomiasis mansoni in Brazil: a comparative study

Few publications have compared ultrasound (US) to histology in diagnosing schistosomiasis-induced liver fibrosis (LF); none has used magnetic resonance (MR). The aim of this study was to evaluate schistosomal LF using these three methods. Fourteen patients with hepatosplenic schistosomiasis admitted to hospital for surgical treatment of variceal bleeding were investigated. They were submitted to upper digestive endoscopy, US, MR and wedge liver biopsy. The World Health Organization protocol for US in schistosomiasis was used. Hepatic fibrosis was classified as absent, slight, moderate or intense. Histology and MR confirmed Symmers' fibrosis in all cases. US failed to detect it in one patient. Moderate agreement was found comparing US to MR; poor agreement was found when US or MR were compared to histology. Re-classifying LF as only slight or intense created moderate agreement between imaging techniques and histology. Histomorphometry did not separate slight from intense LF. Two patients with advanced hepatosplenic schistosomiasis presented slight LF. Our data suggest that the presence of the characteristic periportal fibrosis, diagnosed by US, MR or histology, associated with a sign of portal hypertension, defines the severity of the disease. We conclude that imaging techniques are reliable to define the presence of LF but fail in grading its intensity

Avaliação dos marcadores séricos - ácido hialurônico (AH), YKL40 e fator de crescimento e transformação 1 (TGF-1) - no diagnóstico da esquistossomose mansônica hepatoesplênica

Exportado OPUSMade available in DSpace on 2019-08-12T07:59:56Z (GMT). No. of bitstreams: 1 tese_izabella___17_12_2012_final.pdf: 1973429 bytes, checksum: 8c40908492e80c6467b244ee1f4a6ddf (MD5) Previous issue date: 2Introdução: Biomarcadores séricos têm sido usados no diagnóstico e avaliação da intensidade da fibrose na esquistossomose hepatoesplênica com resultados variados. Poucos estudos usaram a biópsia hepática na confirmação da presença de fibrose de Symmers e mais frequentemente utilizaram-se métodos de imagem como padrão ouro. Objetivo: Avaliamos neste estudo o papel do ácido hialurônico (AH), do YKL40 e do fator de crescimento e transformação 1 (TGF-1) no diagnóstico da esquistossomose mansônica hepatoesplênica e na avaliação da intensidade da fibrose hepática utilizando métodos de imagem e biópsia hepática cirúrgica. Metodologia: Sessenta pacientes com esquistossomose mansônica foram selecionados para o estudo. Trinta (Grupo 1) tinham esquistossomose hepatoesplênica e frequentavam o ambulatório de Doenças Infecciosas e Parasitárias da UFMG (estes pacientes não tinham evidência de infecção ativa pelo S. mansoni); 23 eram homens (76,7%), com média de idade de 39,2 anos (± 9,7). Outros 30 pacientes tinham esquistossomose hepatointestinal (Grupo 2) e eram provenientes de área endêmica de esquistossomose (ovos viáveis nas fezes); 15 eram homens (50%), com média de idade de 35,5 anos (±12,7). Todos foram submetidos a exame clínico, ultrassonografia abdominal e coleta de sangue para a realização dos marcadores séricos de fibrose. Os hepatoesplênicos (Grupo 1) submeteram-se a outros exames, como: marcadores sorológicos de hepatites B e C, endoscopia digestiva alta, ressonância magnética do abdome e biópsia hepática em cunha durante o ato cirúrgico para tratamento de hipertensão porta. Os marcadores séricos foram dosados pelo método de ELISA utilizando kits comerciais. Para a ultrassonografia usou-se o aparelho ALOKA SSD 1700 Dynaview e para a ressonância magnética o aparelho da General Eletric (GE) 1.5 tesla. Os fragmentos de fígado obtidos durante a cirurgia foram conservados em formol a 10% e a seguir emblocados em parafina. Os cortes de 5m (micrômetros) corados pela HE foram analisados à microscopia de luz. Para a histomorfometria usou-se o corante picrossírius vermelho e as áreas examinadas foram quantificadas usando-se o software Image-Pro-Plus. Os dados obtidos foram armazenados no programa EpiData 3.0 e analisados pelo software R Project for Statistical Computing, versão 2.14.0. Resultados: O ácido hialurônico (AH) e o YKL40 não tiveram valor no diagnóstico da fibrose hepática da esquistossomose (não separaram os hepatoesplênicos dos hepatointestinais), quando comparados aos métodos de imagem. A distribuição dos valores de TGF-1 foi maior no grupo de pacientes com esquistossomose hepatointestinal (p= 0,0001). A classificação da intensidade da fibrose hepática na histologia não coincidiu com os valores séricos dos marcadores avaliados neste estudo. Observou-se correlação moderada dos níveis séricos de AH com a histomorfometria (p= 0,006). Houve boa concordância entre os métodos de imagem e a biópsia hepática na classificação da intensidade da fibrose. Conclusões: O ácido hialurônico e o YKL40 não separaram os pacientes com fibrose dos pacientes sem fibrose hepática. O TGF-1 não teve importância como marcador de fibrose hepática nos hepatoesplênicos, mas apresentou níveis séricos significativamente mais elevados nos pacientes com esquistossomose hepatointestinal. Isso sugere que ele seja marcador de infecção ativa pelo S. mansoni. Os marcadores usados neste estudo não foram importantes na classificação da intensidade da fibrose hepática esquistossomótica.Introduction: Serum biomarkers have been used as a tool in the diagnosis and evaluation of liver fibrosis intensity in hepatosplenic schistosomiasis with variable results. Few studies have used liver biopsy in the confirmation of Symmers' fibrosis and more frequently physicians rely upon imaging techniques as gold standard in the evaluation of liver fibrosis severity. Objective: Herein we evaluated the importance of hyaluronic acid (HA), YKL-40 and transforming growth factor Beta1 (TGF-1) in the diagnosis of hepatosplenic schistosomiasis and in the evaluation of liver fibrosis intensity using imaging techniques and surgical wedge liver biopsy. Methodology: Sixty patients with schistosomiasis mansoni were selected for this study. Thirty (Group 1) had hepatosplenic schistosomiasis and they were attending the Centro de Treinamento e Referência em Doenças Infecciosas e Parasitárias, UFMG (patients, in this group, had no evidence of active Schistosoma mansoni infection); 23 were male (76.7%) in the mean age of 39.2 years (±9.7). Another 30 patients had hepatointestinal schistosomiasis (Group 2) and they came from endemic areas of Minas Gerais (with viable eggs in the stool); 15 were male (50.0%), mean age of 35.5 years (±12.7). All patients were submitted to clinical examination and abdominal ultrasound; a blood sample was collected and stored for further analysis. The hepatosplenic group was submitted to other tests, such as: serology for hepatitides B and C, upper digestive endoscopy, abdominal magnetic resonance and surgical liver wedge biopsy. The serum markers of fibrosis were measured using commercial kits. For ultrasound an ALOKA SSD 1700 Dynaview apparatus was used and for magnetic resonance a GE 1.5 tesla instrument. Liver fragments obtained during surgery were fixed in 10% buffered formalin and afterwards embedded in paraffin wax. Five m (micrometers) slices were stained using Hematoxylin-Eosin and examined under light microscopy. Other fragments were stained with Picrosirius red and portal tracts were selected by the examiner and quantified by the software Image-Pro-Plus. Collected data were stored in EpiData 3.1 and the software R Project for Statistical Computing, 2.14.0 version was used for statistical analysis. Results: Both hyaluronic acid and YKL40 had no value in the diagnosis of liver fibrosis (they did not separate patients with hepatosplenic from hepatointestinal schistosomiasis) when imaging techniques were used for liver fibrosis identification. Serum levels of TGF-B1 were higher in the sera of patients with hepatointestinal schistosomiasis compared to patients with the hepatosplenic form of the disease. Intensity of liver fibrosis classified by histology did not coincide with serum levels of the biomarkers evaluated in this study. There was moderate correlation between serum levels of hyaluronic acid when it was compared to histomorphometry (p=0.006). There was a good concordance between imaging techniques and liver biopsy in the classification of liver fibrosis intensity. Conclusions: Hyaluronic acid and YKL40 were not useful as a marker of liver fibrosis in our study. TGF- 1, also, was not a good marker of liver fibrosis but its serum levels were significantly higher in patients with hepatointestinal schistosomiasis as compared to hepatosplenics. Therefore, TGF-1 may be a marker of active S. mansoni infection. The biomarkers used in the present study were not important in classifying schistosomiasis liver fibrosis severity