EDUARDO LUIZ RACHID CANCADO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
P ICHC, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
P ICHC, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina
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- Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis(2022) CANCADO, Guilherme Grossi Lopes; BRAGA, Michelle Harriz; FERRAZ, Maria Lucia Gomes; VILLELA-NOGUEIRA, Cristiane Alves; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; GOMES, Nathalia Mota de Faria; OLIVEIRA, Elze Maria Gomes; ROTMAN, Vivian; OLIVEIRA, Maria Beatriz; CUNHA, Simone Muniz Carvalho Fernandes da; CUNHA-SILVA, Marlone; MENDES, Liliana Sampaio Costa; IVANTES, Claudia Alexandra Pontes; CODES, Liana; BORGES, Valeria Ferreira; PACE, Fabio Heleno de Lima; PESSOA, Mario Guimaraes; SIGNORELLI, Izabelle Venturini; CORAL, Gabriela Perdomo; BITTENCOURT, Paulo Lisboa; LEVY, Cynthia; COUTO, Claudia AlvesBackground Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated. Aims The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort. Methods The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status. Results A total of 464 subjects (95.4% females, mean age 56 +/- 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 +/- 14 vs. 59.6 +/- 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 +/- 13 vs. 49.5 +/- 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 +/- 183 vs. 383.2 +/- 378 mg/dL, p = 0.01) and triglycerides (107.6 +/- 59.8 vs.129.3 +/- 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 +/- 13.5 vs. 1.8 +/- 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups. Conclusions AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.
- Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis(2021) CRESCENTE, Juliana Goldbaum; DELLAVANCE, Alessandra; DINIZ, Marcio Augusto; CARRILHO, Flair Jose; ANDRADE, Luis Eduardo Coelho de; CANCADO, Eduardo Luiz RachidOBJECTIVES: To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS: For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS: There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p < 0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBDpatients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase. CONCLUSIONS: PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing.
conferenceObject ANTI-MITOCONDRIAL-NEGATIVE PRIMARY BILIARY CHOLANGITIS: SPECTRUM OF THE SAME DISEASE?(2021) CANCADO, Guilherme Grossi Lopes; BRAGA, Michelle Harriz; FERRAZ, Maria Gomes; VILLELA-NOGUEIRA, Cristiane Alves; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; GOMES, Nathalia Mota De Faria; OLIVEIRA, Elze Maria G.; ROTMAN, Vivian; OLIVEIRA, Maria Beatriz; CUNHA, Simone Muniz Carvalho Fernandes Da; CUNHA-SILVA, Marlone; MENDES, Liliana; IVANTES, Claudia Alexandra Pontes; CODES, Liana; BORGES, Valeria Ferreira De Almeida E; PACE, Fabio Heleno De Lima; PESSOA, Mario Guimaraes; SIGNORELLI, Izabelle Venturini; CORAL, Gabriela Perdomo; BITTENCOURT, Paulo L.; LEVY, Cynthia; COUTO, Claudia Alves- Chloroquine Is Effective for Maintenance of Remission in Autoimmune Hepatitis: Controlled, Double-Blind, Randomized Trial(2019) TERRABUIO, Debora Raquel Benedita; DINIZ, Marcio Augusto; FALCAO, Lydia Teofilo de Moraes; GUEDES, Ana Luiza Vilar; NAKANO, Larissa Akeme; EVANGELISTA, Andreia Silva; LIMA, Fabiana Roberto; ABRANTES-LEMOS, Clarice Pires; CARRILHO, Flair Jose; CANCADO, Eduardo Luiz RachidBetween 50% and 86% of patients with autoimmune hepatitis (AIH) relapse after immunosuppression withdrawal; long-term immunosuppression is associated with increased risk of neoplasias and infections. Chloroquine diphosphate (CQ) is an immunomodulatory drug that reduces the risk of flares in rheumatologic diseases. Our aims were to investigate the efficacy and safety of CQ for maintenance of biochemical remission of AIH in a double-blind randomized trial and to define a subgroup that obtained a greater benefit from its use. A total of 61 patients with AIH in histologic remission (90.1% AIH type 1 [AIH-1]) were randomized to receive CQ 250 mg/day or placebo for 36 months. Of the 61 patients, 31 received CQ and 30 placebo. At baseline, clinical, laboratory, histologic findings, and human leukocyte antigen (HLA) profile were similar between the two groups. Relapse-free survival was significantly higher in the CQ group compared to the placebo group (59.3% and 19.9%, respectively P = 0.039). For those patients completing 3-year treatment, relapse rates were 41.6% and 0% after CQ and placebo withdrawal, respectively. Factors associated with a higher risk of relapse in multiple Cox regression were placebo use (hazard ratio, 2.4; 95% confidence interval [CI], 1.055.5; P = 0.039) and anti-soluble liver antigen/liver-pancreas (anti-SLA/LP) seropositivity (hazard ratio, 5.4; 95% CI, 1.91-15.3; P = 0.002). Although it was not possible to define a subgroup that obtained a greater benefit from CQ according to anti-SLA/LP reactivity or HLA profile, 100% of patients who were anti-SLA/LP-positive (+) relapsed with placebo compared to 50% with CQ (P = 0.055). In the CQgroup, 54.8% had side effects and 19.3% interrupted the drug regimen. Conclusion: CQ safely reduced the risk of relapse of AIH, but it was not possible to define a subgroup that obtained a greater benefit with CQ use, probably because of sample size.
- Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study(2022) CANCADO, Guilherme Grossi Lopes; COUTO, Claudia Alves; GUEDES, Laura Vilar; BRAGA, Michelle Harriz; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; FERRAZ, Maria Lucia Gomes; VILLELA-NOGUEIRA, Cristiane Alves; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; OLIVEIRA, Elze Maria Gomes de; ROTMAN, Vivian; MAZO, Daniel Ferraz de Campos; BORGES, Valeria Ferreira de Almeida e; MENDES, Liliana Sampaio Costa; CODES, Liana; PESSOA, Mario Guimaraes; SIGNORELLI, Izabelle Venturini; LEVY, Cynthia; BITTENCOURT, Paulo LisboaAim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC.Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria.Results: In total, 27 patients (100% women, mean age 48.9 +/- 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria.Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.
- Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis(2023) CANCADO, Guilherme Grossi Lopes; COUTO, Claudia Alves; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; VILLELA-NOGUEIRA, Cristiane Alves; FERRAZ, Maria Lucia Gomes; BRAGA, Michelle Harriz; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; GOMES, Nathalia Mota de Faria; OLIVEIRA, Elze Maria Gomes; ROTMAN, Vivian; OLIVEIRA, Maria Beatriz; CUNHA, Simone Muniz Carvalho Fernandes da; CUNHA-SILVA, Marlone; MENDES, Liliana Sampaio Costa; IVANTES, Claudia Alexandra Pontes; CODES, Liana; BORGES, Valeria Ferreira de Almeida E; PACE, Fabio Heleno de Lima; PESSOA, Mario Guimaraes; GUEDES, Laura Vilar; SIGNORELLI, Izabelle Venturini; CORAL, Gabriela Perdomo; LEVY, Cynthia; BITTENCOURT, Paulo LisboaBackground Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. Aims This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. Methods Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. Results 206 patients with PBC (96.6% women; mean age 54 +/- 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 +/- 1.95 times the upper limit of normal (x ULN) among responders versus 5.05 +/- 3.08 x ULN in non-responders (p < 0.001). Conclusions After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.
- Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population(2022) CANCADO, Guilherme Grossi Lopes; BRAGA, Michelle Harriz; FERRAZ, Maria Lucia Gomes; VILLELA-NOGUEIRA, Cristiane Alves; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; GOMES, Nathalia Mota de Faria; OLIVEIRA, Elze Maria Gomes de; ROTMAN, Vivian; OLIVEIRA, Maria Beatriz de; CUNHA, Simone Muniz Carvalho Fernandes da; MAZO, Daniel Ferraz de Campos; MENDES, Liliana Sampaio Costa; IVANTES, Claudia Alexandra Pontes; CODES, Liana; BORGES, Valeria Ferreira de Almeida e; PACE, Fabio Heleno de Lima; PESSOA, Mario Guimaraes; SIGNORELLI, Izabelle Venturini; CORAL, Gabriela Perdomo; BITTENCOURT, Paulo Lisboa; LEVY, Cynthia; COUTO, Claudia AlvesIntroduction and objectives: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. Material and methods: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. Results: 562 patients (95% females, mean age 51 +/- 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 +/- 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histologi -cal stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates. Conclusions: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Cauca-sians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization. (c) 2021 Fundacion Clinica Medica Sur, A.C.
- Efficacy and safety of chloroquine plus prednisone for the treatment of autoimmune hepatitis in a randomized trial(2020) FALCAO, Lydia T. de Moraes; TERRABUIO, Debora R. B.; DINIZ, Marcio A.; EVANGELISTA, Andreia da Silva; SOUZA, Fabricio G.; CANCADO, Eduardo L. R.Background and Aim Standard treatment for autoimmune hepatitis (AIH) consists of predniso(lo)ne and azathioprine. However, alternative therapy is required for non- or partial responders and in cases of side effects. The aim of this study was to evaluate the treatment outcomes associated with chloroquine plus prednisone in AIH patients. Methods Fifty-seven patients were recruited to receive either azathioprine or chloroquine, both with prednisone, in a randomized trial. The primary end-point was complete remission, based on normalization of aminotransferase levels in the first 6 months of treatment plus maintenance for at least 18 months, with minimal or no inflammatory activity in the liver biopsy. Secondary end-points were partial and nonresponse, severe side effects, and treatment withdrawal. Results There were no differences between groups regarding clinical, serological, histological, and treatment characteristics at baseline. There were no significant differences in the biochemical response rate (67.7 vs 53.8%, P = 0.41) or the complete remission rate (32.26 vs 15.38%, P = 0.217). However, despite the long study period, the sample size was smaller than that required for a noninferiority study. The mean prednisone dose was similar in both groups. There was a nonsignificantly higher rate of adverse effects and a tendency toward improvement in glycemic and cholesterol profiles in the chloroquine group (P = 0.09 and P = 0.07, respectively). Conclusions The combination of chloroquine and prednisone exhibited potentially beneficial effects in AIH patients (: NCT02463331).
- Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver(2015) BITTENCOURT, Paulo Lisboa; CANÇADO, Eduardo Luiz Rachid; COUTO, Cláudia Alves; LEVY, Cynthia; PORTA, Gilda; SILVA, Antônio Eduardo Benedito; TERRABUIO, Debora Raquel Benedita; CARVALHO FILHO, Roberto José de; CHAVES, Dalton Marques; MIURA, Irene Kazue; CODES, Liana; FARIA, Luciana Costa; EVANGELISTA, Andreia Silva; FARIAS, Alberto Queiroz; GONÇALVES, Luciana Lofêgo; HARRIZ, Michele; LOPES NETO, Edmundo Pessoa A; LUZ, Gustavo Oliveira; OLIVEIRA, Patrícia; OLIVEIRA, Elze Maria Gomes de; SCHIAVON, Janaina Luz Narciso; SEVA-PEREIRA, Tiago; PARISE, Edison RobertoABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.
conferenceObject RESPONSE TO URSODEOXYCHOLIC ACID SHOULD BE ASSESSED EARLIER TO ALLOW ADD-ON SECOND-LINE THERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS UNRESPONSIVE TO INITIAL TREATMENT(2021) CANCADO, Guilherme Grossi Lopes; BITTENCOURT, Paulo L.; BRAGA, Michelle Harriz; FERRAZ, Maria Gomes; VILLELA-NOGUEIRA, Cristiane Alves; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; GOMES, Nathalia Mota De Faria; OLIVEIRA, Elze Maria G.; ROTMAN, Vivian; OLIVEIRA, Maria Beatriz; CUNHA, Simone Muniz Carvalho Fernandes Da; CUNHA-SILVA, Marlone; MENDES, Liliana; IVANTES, Claudia Alexandra Pontes; CODES, Liana; BORGES, Valeria Ferreira De Almeida E.; PACE, Fabio Heleno De Lima; PESSOA, Mario Guimaraes; SIGNORELLI, Izabelle Venturini; CORAL, Gabriela Perdomo; LEVY, Cynthia; COUTO, Claudia Alves