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 16 Citação(ões) na Scopus
    The importance of autoantibody detection in primary biliary cirrhosis
    (2015) CANCADO, Eduardo Luiz Rachid; HARRIZ, Michelle
  • article 1 Citação(ões) na Scopus
    HLA-related genetic susceptibility in autoimmune hepatitis according to autoantibody profile
    (2022) CANCADO, Eduardo Luiz Rachid; GOLDBAUM-CRESCENTE, Juliana; TERRABUIO, Debora Raquel B.
    Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA), and susceptibility to this disease, has been studied for over three decades. The genetic susceptibility to AIH is believed to be different in the two subtypes of the disease, AIH type 1 and AIH type 2. Type 1 AIH has anti-smooth muscle and anti-nuclear antibodies as its main markers, while those of type 2 AIH are the anti-liver/kidney microsome type 1 and anti-liver cytosol type 1 antibodies. The anti-soluble liver antigen/liver-pancreas antibodies, which, in addition to being present in both subtypes, mark an important number of patients without serological markers. Therefore, a third type of disease is questionable. The vast majority of immunogenetic studies compare the differences between the two main types and make no difference between which antibodies are present to define the subtype. This review seeks to analyze what was most important published in the AIH in this context, trying to relate the HLA alleles according to the AIH marker autoantibodies.
  • 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
    Azathioprine-related severe diarrhea induced by high levels of 6-thioguanine nucleotides in renal transplant recipient carrying mutant thiopurine methyltransferase: a case report
    (2012) PACHECO-NETO, Maurílio; NASSER, Paulo D.; ALVES, Atecla N. L; FORTINI, Alexandre S.; SUMITA, Nairo M.; MENDES, Maria E.; ONO-NITA, Suzane K.; CANÇADO, Eduardo L. R.; TORRES, Larissa H. L.; DULEY, John A.; NAHAS, William C.; CHOCAIR, Pedro R.
    Introduction: Azathioprine (AZA) is widely used to prevent rejection in organ transplants and treat auto-immune diseases. The major side effects reported for the use of AZA are myelotoxicity, hepatotoxicity, and flu-like symptoms, while there are a few reports of severe diarrhea. Thiopurine methyltransferase (TPMT) is a major catabolic route that has pharmacogenetic importance. We describe here the evolution of a renal transplant recipient carrying a mutant TPMT allele, who developed severe diarrhea related to the use of AZA and high levels of 6-TGN. Case presentation: A 28-year-old Brazilian Caucasian man underwent preemptive renal transplant in 2006 and presented persistent diarrhea. Therapeutic drug monitoring (TDM) of AZA metabolites indicated high levels of red blood cell 6-TGN, and AZA was discontinued in view of the patient’s persistent diarrhea. Normalization of bowel habit was gradual, parallel to the patient’s physical condition. TPMT genotype showed the mutant allele TPMT*1/*3A, genotype associated with low enzymatic activity, high levels of 6-TGN and consequently high susceptibility to side effects. Discussion: AZA has been empirically used for about 50 years, even though the pharmacokinetics is demonstrably variable among individuals. It is known that AZA has a higher selectivity for rapidly multiplying cells, which also implies higher toxicity. So it can be inferred that the high levels of 6-TGN were causing damage to the patient’s intestinal mucosa. This report shows that TDM of AZA may be useful for differential diagnosis of the cause of less frequent adverse events, such as diarrhea.