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- Severity of Ascites Is Associated with Increased Mortality in Patients with Cirrhosis Secondary to Biliary AtresiaPublication . Guedes, Renata R.; Kieling, Carlos; Santos, Jorge Luiz dos; Rocha, Carolina da; Schwengber, Fernando; Adami, Marina R.; Chedid, Marcio F.; Vieira, Sandra M. G.Background Very few prior studies have investigated the presence of ascites as a prognostic factor in children with cirrhosis. To the best of our knowledge, there are no prior studies evaluating the relationship between severity of ascites and patient survival in children with biliary atresia and cirrhosis. Aims To evaluate the association between severity of ascites and survival of children with cirrhosis and biliary atresia. Methods All children with cirrhosis secondary to biliary atresia evaluated at our institution from 2000 to 2014 were included in this study. Patients were classified into four groups: NA = no ascites; A1 = grade 1 ascites; A2 = grade 2 ascites; and A3 = grade 3 ascites. The primary endpoint of the study was mortality within the first year after patient inclusion. Ninetyday mortality was also evaluated. Prognostic factors related to both endpoints also were studied. [...]
- Visualizing Structures in Confocal Microscopy Datasets Through Clusterization: A Case Study on Bile DuctsPublication . Beltran, Lizeth A.C.; Cruz, Carolina U.; Santos, Jorge Luiz dos; Shivakumar, Pranavkumar; Bezerra, Jorge; Freitas, Carla M.D.S.Abstract—Three-dimensional datasets from biological tissues have increased with the evolution of confocal microscopy. Hepatology researchers have used confocal microscopy for investigating the microanatomy of bile ducts. Bile ducts are complex tubular tissues consisting of many juxtaposed microstructures with distinct characteristics. Since confocal images are difficult to segment because of the noise introduced during the specimen preparation, traditional quantitative analyses used in medical datasets are difficult to perform on confocal microscopy data and require extensive user intervention. Thus, the visual exploration and analysis of bile ducts pose a challenge in hepatology research, requiring different methods. This paper investigates the application of unsupervised machine learning to extract relevant structures from confocal microscopy datasets representing bile ducts. Our approach consists of pre-processing, clustering, and 3D visualization. For clustering, we explore the density-based spatial clustering for applications with noise (DBSCAN) algorithm, using gradient information for guiding the clustering. We obtained a better visualization of the most prominent vessels and internal structures.
- Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in ratsPublication . Moreira, Andrea Janz; Rodrigues, Graziella Ramos; Bona, Silvia; Fratta, Leila Xavier Sinigaglia; Weber, Giovana Regina; Picada, Jaqueline Nascimento; Santos, Jorge Luiz dos; Cerski, Carlos Thadeu; Marroni, Claudio Augusto; Marroni, Norma PossaHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis.
- Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomesPublication . Porta, Gilda; Carvalho, Elisa; Santos, Jorge Luiz Dos; Gama, Jorge; Borges, Cristian V.; Seixas, Renata; Ferreira, Alexandre; Miura, Irene; Silveira, Themis Reverbel; Silva, Luciana; Fagundes, Eleonora; Brandao, MA Bellomo; Sawamura, Regina; Vieira, Sandra; Melere, Melina; Marques, Cibele D F; Pugliese, Renata P.; Danesi, Vera; Porta, Adriana; Marsillac, Marise; Valladares, Marcia Angélica; Menezes, Daniela G.; Kieling, Carlos; Paula, Mariana N. de; Vasconcelos, Juliana R.; Ferreira, Cristina T.; Perin, Nilza; Resende, Leonardo R.; Maia, Jussara; Tommaso, Adriana M.A. De; Hessel, Gabrielsentation, laboratory findings, histological profile, treatments, and outcomes of children andadolescents with autoimmune hepatitis.Methods: The medical records of 828 children and adolescents with autoimmune hepatitiswere reviewed. A questionnaire was used to collect anonymous data on clinical presentation,biochemical and histological findings, and treatments.Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmunehepatitis-2. The female sex was predominant in both groups. The median age at symptomonset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher forautoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patientswith autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-foldhigher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were sig-nificantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels werelower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochem-ical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6%underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmunehepatitis-2: 2.4%).Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.
- Environmental risk factors associated with biliary atresia in Rio Grande do sul, BrazilPublication . Longo, Larisse; Ferrari, Jéssica Tonin; Hoss, Giovana Regina Weber; Fratta, Leila Xavier Sinigaglia; Vieira, Sandra Maria Gonçalves; Silveira, Themis Reverbel da; Silva, Fernando Antônio de Abreu e; Sanseverino, Maria Teresa; Santos, Jorge Luiz dosBiliary atresia (BA) seems to be a multifactorial disorder in which environmental factors interact with the patient’s genetic constitution. This study aimed to analyze information concerning environmental risk factors associated with BA in southern Brazil. A case-control study with mothers of patients with BA and mothers of patients with cystic fibrosis (CF) was conducted. Inquiry included questions related to exposition to environmental risk factors during the periconceptional and gestational (second and third trimesters) periods. Mothers of BA patients had smoked during pregnancy more frequently in comparison with the mothers of CF patients, but no significant difference was found in a multivariate analysis. There was no between group difference in terms of seasonality, but the multivariate analysis showed a significant difference within the BA group between date of conception in winter compared to other seasons. In conclusion, smoking during pregnancy seemed to increase the risk of BA while date of conception in winter decreased it.