EDUARDO LUIZ RACHID CANCADO

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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

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  • article 8 Citação(ões) na Scopus
    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 Alves
    Background 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.
  • article 78 Citação(ões) na Scopus
    Antismooth Muscle and Antiactin Antibodies Are Indirect Markers of Histological and Biochemical Activity of Autoimmune Hepatitis
    (2014) COUTO, Claudia A.; BITTENCOURT, Paulo L.; PORTA, Gilda; ABRANTES-LEMOS, Clarice P.; CARRILHO, Flair J.; GUARDIA, Bianca D.; CANCADO, Eduardo L. R.
    Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P<0.001). Conclusion: With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. (Hepatology 2014;59:592-600)
  • article 2 Citação(ões) na Scopus
    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 Rachid
    OBJECTIVES: 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.
  • article 1 Citação(ões) na Scopus
    Liver elastography can predict degree of advanced fibrosis for autoimmune hepatitis in biochemical remission
    (2023) PARANAGUA-VEZOZZO, Denise Cerqueira; TERRABUIO, Debora Raquel Benedita; REINOSO-PEREIRA, Gleicy Luz; MOUTINHO, Renata; ONO, Suzane Kioko; SALAS, Veronica Walwyn; FRANCA, Joao Italo Dias; ALVES, Venancio Avancini Ferreira; CANCADO, Eduardo Luiz Rachid; CARRILHO, Flair Jose
    Background and AimThe aim was to analyze the concordance of liver stiffness measurement (LSM) either by transient elastography (TE) or ARFI with liver biopsy in autoimmune hepatitis (AIH) patients with biochemical remission and to identify those with histological remission. Liver biopsy is still the golden standard for AIH diagnosis. However, it is an invasive procedure and these patients, most of the time, require many biopsies, so it would be valuable to search for noninvasive method that could select all these patients and keep under observation. MethodsThirty-three patients with AIH were submitted for liver biopsy to evaluate histological remission after at least 18 months of normal aminotransferases. The efficiency of LSM and fibrosis stages was tested by a receiver operating characteristic curve analysis (AUROC). ResultsOne patient (3%) was F0, 6 (18.2%) were F1, 8 (24.2%) were F2, 10 (30.3%) were F3, and 8 (24.2%) were F4, according to METAVIR. Thirteen of thirty-three (39.4%) patients did not achieve histological remission. AUROC for F4 stage was 0.83 (IC: 0.76-0.99) for TE and 0.78 (IC: 0.65-0.95) for ARFI. Optimal LSM cutoff values were 12.3 kPa (Se = 87.5%, Sp = 88%) for TE and 1.65 m/s (Se = 87.5%, Sp = 76%) for ARFI. The tests were unable to differentiate patients with histological activity from those in histological remission (P < 0.05). ConclusionTE and ARFI accurately identify liver fibrosis by METAVIR score in AIH patients with biochemical remission. No cutoff value was detected to indicate whether the patient achieved histological remission.
  • article 38 Citação(ões) na Scopus
    Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis
    (2013) CALICH, Ana L.; VIANA, Vilma S. T.; CANCADO, Eduardo; TUSTUMI, Francisco; TERRABUIO, Debora R. B.; LEON, Elaine P.; SILVA, Clovis A.; BORBA, Eduardo F.; BONFA, Eloisa
    Background Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE-associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. Aims To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. Methods Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n=1) and anti-Sm (n=2) were excluded. Results Moderate to high titres (>40U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P=0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4 vs. 28.5%, P=0.44), hepatic laboratorial findings (0.05). Importantly, at the final observation (follow-up period 10.2 +/- 4.9years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared with the negative group (100 vs. 60%, P=0.04). Conclusion The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses.
  • article 11 Citação(ões) na Scopus
    The importance of autoantibody detection in autoimmune hepatitis
    (2015) CANCADO, Eduardo Luiz Rachid; ABRANTES-LEMOS, Clarice Pires; TERRABUIO, Debora Raquel B.
  • article 19 Citação(ões) na Scopus
    Primary Adrenal Insufficiency Due to Bilateral Adrenal Infarction in COVID-19
    (2022) MACHADO, Iza F. R.; MENEZES, Isabel Q.; FIGUEIREDO, Sabrina R.; COELHO, Fernando M. A.; TERRABUIO, Debora R. B.; V, Davi Ramos; FAGUNDES, Gustavo F. C.; MACIEL, Ana Alice W.; LATRONICO, Ana Claudia; V, Maria Candida B. Fragoso; CANCADO, Eduardo L. R.; MENDONCA, Berenice B.; ALMEIDA, Madson Q.
    Context: Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated. Case report: A 46-year-old woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 mu g/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone. Discussion: We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19. Conclusion: Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.
  • article 13 Citação(ões) na Scopus
    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 Rachid
    Between 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.
  • article 3 Citação(ões) na Scopus
    Clinical Features and Outcomes of Primary Sclerosing Cholangitis in the Highly Admixed Brazilian Population
    (2021) NARDELLI, Mateus Jorge; BITTENCOURT, Paulo Lisboa; CANCADO, Guilherme Grossi Lopes; FARIA, Luciana Costa; VILLELA-NOGUEIRA, Cristiane Alves; ROTMAN, Vivian; ABREU, Eliabe Silva de; OSORIO, Fernanda Maria Farage; EVANGELISTA, Andreia Silva; MENDES, Liliana Sampaio Costa; MAZO, Daniel Ferraz de Campos; HYPPOLITO, Elodie Bonfim; MARTINS, Adrielly de Souza; CODES, Liana; SIGNORELLI, Izabelle Venturini; GOMIDE, Geisa Perez Medina; AGOGLIA, Luciana; IVANTES, Claudia Alexandra Pontes; BORGES, Valeria Ferreira de Almeida E; CORAL, Gabriela Perdomo; REZENDE, Rosamar Eulira Fontes; FERRAZ, Maria Lucia Gomes; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz Rachid; COUTO, Claudia Alves
    Background. Primary sclerosing cholangitis (PSC) is associated with a broad phenotypic spectrum in different populations from diverse ethnic and racial backgrounds. This study aimed to describe the clinical characteristics and outcomes of PSC in a multicenter cohort of patients from Brazil. Methods. Data from the Brazilian Cholestasis Study Group were retrospectively reviewed to assess demographic information and clinical characteristics of PSC, as well as the outcomes, such as transplantation-free survival. Results. This cohort included 210 patients. After excluding 33 (15.7%) patients with PSC and overlap syndrome of autoimmune hepatitis, 177 (97 males, median age 33 (21-42) years) with clear-cut PSC were eligible for this study. Most of the patients (n = 139, 78.5%) were symptomatic, and 104 (58.7%) had advanced PSC at the time of diagnosis. Concurrent inflammatory bowel disease was observed in 78 (58.6%) of the investigated patients (n = 133), and most of them had ulcerative colitis (n = 61, 78.2%). The 1- and 5-year survival free of liver transplantation or death were 92.3 +/- 2.1% and 66.9 +/- 4.2%, respectively, and baseline advanced PSC, pruritus, and elevated bilirubin levels were independent risk factors for the composite adverse outcome. Females were significantly older and had lower bilirubin levels than males at baseline, but survival was not associated with sex. Approximately 12.4% (n = 22) of patients with PSC died, and 32.8% (n = 58) underwent liver transplantation at a median follow-up time of 5.3 and 3.2 years. Conclusion. Multiethnic Brazilian PSC patients exhibited a less pronounced male predominance and a lower frequency of inflammatory bowel disease than Caucasians. Adverse outcomes were more frequent, probably due to advanced disease at baseline.
  • article 18 Citação(ões) na Scopus
    Wilson's disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene
    (2013) BEM, Ricardo Schmitt de; RASKIN, Salmo; MUZZILLO, Dominique Araujo; DEGUTI, Marta Mitiko; CANCADO, Eduardo Luiz Rachid; ARAUJO, Thiago Ferreira; NAKHLE, Maria Cristina; BARBOSA, Egberto Reis; MUNHOZ, Renato Puppi; TEIVE, Helio Afonso Ghizoni
    Objective: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. Methods: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. Results: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. Conclusion: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.