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1.
Blood Cancer J ; 11(8): 142, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376633

RESUMO

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , Comorbidade , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto Jovem
2.
J Transl Med ; 14: 17, 2016 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-26774260

RESUMO

BACKGROUND: The challenging diagnosis and poor prognosis of cholangiocarcinoma require the determination of biomarkers. Autoantibodies could be used in the clinic as diagnostic markers for the early detection of tumours. By proteomic approaches, several autoantibodies were proposed as potential markers. We tried in this study, to perform a serological proteome analysis, using various antigenic substrates, including tumours and human liver. METHODS: Sera from patients (n = 13) and healthy donors (n = 10) were probed on immunoblots performed using 2-dimensionally separated proteins from cholangiocarcinoma cell lines (CCLP1 and CCSW1), from the liver of healthy subject and interestingly, from tumour and adjacent non-tumour liver tissues from five patients with cholangiocarcinoma and tested with their corresponding serum. Spots of interest were identified using mass spectrometry and classified according gene ontology analysis. RESULTS: A comparison of the whole immunoblotting patterns given by cholangiocarcinoma sera against those obtained with normal control sera enabled the definition of 862 spots. Forty-five different proteins were further analysed, corresponding to (1) spots stained with more than four of 13 (30 %) sera tested with the CCLP1 or the CCSW1 cell line and with the normal liver, and (2) to spots immunoreactive with at least two of the five sera probed with their tumour and non-tumour counter-part of cholangiocarcinoma. Immunoreactive proteins with catalytic activity as molecular function were detected at rates of 93 and 64 % in liver from healthy subjects or cholangiocarcinoma non-tumour tissues respectively, compared to 43, 33, 33 % in tumour tissues, or CCSW1 and CCLP1 cell lines. A second pattern was represented by structural proteins with rates of 7 and 7 % in normal liver or non-tumour tissues compared to 14, 33 and 67 % in tumour tissue, CCSW1 or CCLP1 cell lines. Proteins with a binding function were detected at rates of 7 % in non-tumour tissue and 14 % in tumour tissue. Using the extracted tumour tissue, serotransferrin was targeted by all cholangiocarcinoma-related sera. CONCLUSIONS: Immunological patterns depended on the type of antigen substrate used; i.e. tumour versus non tumour specimens. Nevertheless, a combination of multiple autoantibodies tested with the most appropriate substrate might be more sensitive and specific for the diagnosis of cholangiocarcinoma.


Assuntos
Autoanticorpos/sangue , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/imunologia , Colangiocarcinoma/sangue , Colangiocarcinoma/imunologia , Proteoma/metabolismo , Proteômica/métodos , Linhagem Celular Tumoral , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Ontologia Genética , Humanos , Immunoblotting , Fígado/metabolismo , Fígado/patologia , Reprodutibilidade dos Testes
4.
PLoS One ; 8(12): e84600, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24376828

RESUMO

BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH). AIM: To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls. METHODS: Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants k(off) for each interaction were calculated. RESULTS: Several significant interactions were observed: i) high stability (lower k(off) values) between P55₋70 and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher k(off) values) between P118₋133 and P262₋277 and SLE sera, P145₋160 and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and k(off) values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P55₋70 and also between controls and the peptides studied. CONCLUSIONS: These results indicate that P55₋70 of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.


Assuntos
Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Hepatite Autoimune/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Anticorpos Antinucleares/metabolismo , Eletroforese em Gel de Poliacrilamida , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Immunoblotting , Peptídeos/metabolismo , Estatísticas não Paramétricas
8.
Hepatology ; 57(2): 689-99, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22911395

RESUMO

UNLABELLED: The development of potentially severe non-graft-versus-host disease (GVHD) hepatitis resembling autoimmune hepatitis (AIH) has been reported after bone marrow transplantation (BMT). The aim of this study was to better characterize this form of hepatitis, particularly through the identification of autoantigens recognized by patient sera. Five patients who received an allogeneic BMT for the treatment of hematological diseases developed liver dysfunction with histological features suggestive of AIH. Before and during the onset of hepatic dysfunction, sera were tested on immunoblottings performed with cytosolic, microsomal, mitochondrial, and nuclear proteins from rat liver homogenate and resolved by two-dimensional electrophoresis. Antigenic targets were identified by mass spectrometry. During the year that followed BMT, all patients presented with GVHD. Acute hepatitis then occurred after the withdrawal, or during the tapering, of immunosuppressive therapy. At that time, no patients had a history of liver toxic drug absorption, patent viral infection, or any histopathological findings consistent with GVHD. Immunoreactive spots stained by sera collected at the time of hepatic dysfunction were more numerous and more intensely expressed than those stained by sera collected before. Considerable patient-dependent pattern heterogeneity was observed. Among the 259 spots stained exclusively by sera collected at the time of hepatitis, a total of 240 spots were identified, corresponding to 103 different proteins. Twelve of them were recognized by sera from 3 patients. CONCLUSIONS: This is the first immunological description of potentially severe non-GVHD hepatitis occurring after BMT, determined using a proteomic approach and enabling a discussion of the mechanisms that transform an alloimmune reaction into an autoimmune response. Any decision to withdraw immunosuppression after allogeneic BMT should be made with caution.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Hepatite Autoimune/etiologia , Transplante Homólogo/imunologia , Adulto , Animais , Feminino , Doença Enxerto-Hospedeiro/imunologia , Hepatite Autoimune/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Ratos
10.
Clin Res Hepatol Gastroenterol ; 36(4): e57-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22883833

RESUMO

In an 8-year-old boy with biochemical hepatic disorders, an histological examination of a liver biopsy showed a severe chronic hepatitis without cirrhosis. The biliary tract was normal and no toxic or infectious etiologies were found. Spontaneous improvement of the clinical status was observed in the following weeks but biochemical abnormalities were persistent and a second episode occurred 3 years after. Immunological studies showed anti-mitochondrial-2 antibodies (AMA-2) confirmed by an immunoblot performed with rat mitochondrial proteins resolved by two-dimensional electrophoresis. We described here the second case in the literature of paediatric autoimmune hepatitis associated with well documented AMA-2.


Assuntos
Autoanticorpos/sangue , Hepatite Autoimune/sangue , Hepatite Autoimune/imunologia , Proteínas Mitocondriais/imunologia , Biomarcadores/sangue , Criança , Hepatite Autoimune/diagnóstico , Humanos , Masculino
13.
J Hepatol ; 56(4): 840-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22173152

RESUMO

BACKGROUND & AIMS: Most liver transplant centres have discontinued the practice of protocol liver biopsies (LB), mainly because of the perceived lack of therapeutic benefit. This study aimed to examine the usefulness of 20-year LBs. METHODS: Ten, 15, and 20-year protocol LBs from 147 patients surviving for >20 years were reviewed. Twenty-year biopsy findings were correlated with clinical data. RESULTS: Twenty-year-biopsy patients (N=91) and 20-year-non-biopsy patients (N=56) were similar in terms of transplant data, adverse events, and liver function tests (LFTs). Twenty-year LBs revealed a 90% prevalence of abnormalities, among which viral chronic hepatitis (VCH) was the most common (46%). Between 15 and 20 years, hepatic structural abnormalities were the only disorder to increase (p=0.008). An individual progression of abnormalities occurred in 56% of patients. At 20 years, the negative and positive predictive values (PV) of LFTs with respect to histological abnormalities were 95% and 18%, respectively; in VCH, Fibrotest and transient elastography displayed poor discriminative ability for fibrosis (80% and 81% discordance, respectively), but were satisfactory regarding significant fibrosis (negative PV of 77.7% and 80%, respectively). A decrease in immunosuppression was less frequent (14/91 vs. 20/56, p=0.008) while an increase was more common (15/91 vs. 2/56, p=0.017) in 20-year-biopsy patients than in non-biopsy patients. Antiviral therapy was administered in seven of the 20-year biopsy patients, but in none of the non-biopsy patients (p=0.04). CONCLUSIONS: Twenty-year LBs provided important histological information on graft function that was available to a limited degree from LFTs and non-invasive markers. They exerted an impact on immunosuppressive and antiviral therapies.


Assuntos
Progressão da Doença , Sobrevivência de Enxerto , Transplante de Fígado/patologia , Fígado/patologia , Adulto , Biópsia , Feminino , Hepatite Crônica/epidemiologia , Humanos , Fígado/fisiologia , Testes de Função Hepática , Transplante de Fígado/fisiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
15.
Naunyn Schmiedebergs Arch Pharmacol ; 384(4-5): 407-19, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21541759

RESUMO

NME/NDPK family proteins are involved in the control of intracellular nucleotide homeostasis as well as in both physiological and pathological cellular processes, such as proliferation, differentiation, development, apoptosis, and metastasis dissemination, through mechanisms still largely unknown. One family member, NME1/NDPK-A, is a metastasis suppressor, yet the primary physiological functions of this protein are still missing. The purpose of this study was to identify new NME1/NDPK-A-dependent biological functions and pathways regulated by this gene in the liver. We analyzed the proteomes of wild-type and transgenic NME1-null mouse livers by combining two-dimensional gel electrophoresis and mass spectrometry (matrix-assisted laser desorption/ionization time of flight and liquid chromatography-tandem mass spectrometry). We found that the levels of three proteins, namely, phenylalanine hydroxylase, annexin IV, and elongation factor 1 Bα (EF-1Bα), were strongly reduced in the cytosolic fraction of NME1(-/-) mouse livers when compared to the wild type. This was confirmed by immunoblotting analysis. No concomitant reduction in the corresponding messenger RNAs or of total protein level was observed, however, suggesting that NME1 controls annexin IV and EF-1Bα amounts by post-translational mechanisms. NME1 deletion induced a change in the subcellular location of annexin IV in hepatocytes resulting in enrichment of this protein at the plasma membrane. We also observed a redistribution of EF-1Bα in NME1(-/-) hepatocytes to an intracytoplasmic compartment that colocalized with a marker of the reticulum endoplasmic. Finally, we found reduced expression of annexin IV coincident with decreased NME1 expression in a panel of different carcinoma cell lines. Taken together, our data suggest for the first time that NME1 might regulate the subcellular trafficking of annexin IV and EF-1Bα. The potential role of these proteins in metastatic dissemination is discussed.


Assuntos
Anexina A4/metabolismo , Fígado/enzimologia , Nucleosídeo NM23 Difosfato Quinases/fisiologia , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Anexina A4/genética , Western Blotting , Linhagem Celular Tumoral , Citosol/enzimologia , Citosol/metabolismo , Eletroforese em Gel Bidimensional , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Nucleosídeo NM23 Difosfato Quinases/genética , Transporte Proteico , Proteômica , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
16.
Dig Dis Sci ; 56(6): 1794-800, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21221802

RESUMO

BACKGROUND: Because Mycobacterium avium subspecies paratuberculosis (MAP), the etiologic agent of Johne's disease in ruminant, has been identified in the mucosal layer and deeper bowel wall in CD patients, the seroactivity against MAP may define a distinct subset of patients requiring individual treatment. The aim of this study was to assess the performance of anti-MAP antibodies in the diagnostic strategy for CD. METHODS: Two hundred seventy-two individuals were included: 81 with CD, 36 with ulcerative colitis, 35 with coeliac diseases and 120 healthy blood donors. Anti-MAP were detected by ELISA using a purified protein derivative from MAP. Anti-Saccharomyces cerevisiae antibodies (ASCA) were detected by indirect immunofluorescence. RESULTS: The sensitivity and specificity of anti-MAP and ASCA for CD diagnosis were similar (sensitivity: 0.33 ± 0.10 and 0.31 ± 0.10; specificity: 0.96 ± 0.03 and 0.98 ± 0.02, respectively). A combination of these two tests enabled an increase in sensitivity (0.53 ± 0.10), although specificity remained unchanged (0.95 ± 0.04). No correlation was found between anti-MAP positivity and clinical features such as age at onset and the duration of CD, disease location, or intestinal complications. Conversely, extra-intestinal manifestations of CD were statistically associated with a positivity of anti-MAP (48% vs. 24%, P = 0.028), mostly with respect to arthritis (44.5% vs. 13%, P < 0.002). Interestingly, anti-MAP and ASCA were also found in an active form of coeliac disease. CONCLUSION: Our results suggest a complementary role of ASCA and anti-MAP for CD diagnosis and a possible common role of bacteria in small intestinal mucosal damage in CD and coeliac disease.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antifúngicos/sangue , Doença de Crohn/sangue , Doença de Crohn/complicações , Mycobacterium avium subsp. paratuberculosis/imunologia , Saccharomyces cerevisiae/imunologia , Adolescente , Adulto , Idoso , Biomarcadores , Criança , Pré-Escolar , Colite Ulcerativa/sangue , Colite Ulcerativa/complicações , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
17.
Liver Int ; 29(6): 857-64, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19302185

RESUMO

BACKGROUND: Antibodies to soluble liver antigen (SLA)/liver pancreas (LP) are generally considered as highly specific diagnostic markers of type 1 auto-immune hepatitis (AIH-1), and are particularly useful in patients without conventional antibodies. However, the presence of anti-SLA/LP in type 2 auto-immune hepatitis (AIH-2), primary sclerosing cholangitis (PSC) and hepatitis C has recently been reported. The aim was thus to describe the characteristics of anti-SLA/LP-positive patients in the largest series reported to date. METHODS: Sera were selected from the period between 1998 and 2005, based on the presence of antibodies to SLA/LP detected by two methods. The clinical status of patients was determined from their medical records. RESULTS: Eighty-one anti-SLA/LP-positive patients with available clinical data were included: 89% (72/81) had a diagnosis of AIH-1, including 10 (12%) associated with cholestatic diseases (primary biliary cirrhosis in seven cases and PSC in three cases). Six patients (7%) suffered from another liver disease: hepatitis C (n=3) and drug-induced hepatitis (n=3). No specific diagnosis was made in three patients. CONCLUSIONS: Antibodies to SLA/LP are of a major diagnostic value for AIH-1, including paediatric forms and overlap syndromes with cholestatic diseases, but are not found in association with anti-liver/kidney/microsome type 1 or antibodies to liver cytosol type 1. They are rarely present in other liver diseases such as hepatitis C and drug-induced hepatitis.


Assuntos
Anticorpos/imunologia , Autoantígenos/imunologia , Doenças dos Ductos Biliares/diagnóstico , Biomarcadores/sangue , Hepatite Autoimune/diagnóstico , Anticorpos/sangue , Doenças dos Ductos Biliares/imunologia , Western Blotting , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , França , Hepatite Autoimune/imunologia , Humanos , Estudos Retrospectivos
18.
Hepatology ; 47(3): 937-48, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18306218

RESUMO

UNLABELLED: Autoimmune hepatitis (AIH) is a liver disease with circulating autoantibodies predominantly directed against widely held cellular components. Because AIH is a liver-specific disease, autoantibodies against plasma membrane antigens may be involved in its pathogenesis and have been reported; however, no definite identification has been described. We thus investigated the fine specificity of anti-hepatocyte plasma membrane autoantibodies in type 1 AIH (AIH-1) using a proteomic tool. A plasma membrane-enriched fraction was validated using enzymatic activity and western blot analysis experiments. Sera from AIH-1 patients (n = 65) and from 90 controls, that is, healthy blood donors (n = 40) and patients with systemic diseases (n = 20) or other liver diseases (n = 30), were studied by immunoblot performed with plasma membrane proteins resolved by either sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or 2-dimensional (2D) electrophoresis. Proteins contained in the immunoreactive spots were identified by sequences provided by ion-trap mass spectrometry. Hepatocytes probed with sera were also studied using confocal immunofluorescence and immunoelectron microscopy. The more prominent bands stained by patient sera were located at 38 kDa, 48, 50, 52 kDa, 62 kDa, 70 kDa, and a 95-kDa double band. Six proteins with known potential plasma membrane expression were identified: liver arginase (38 kDa), cytokeratins (CK) 8 and 18 (48-52 kDa), heat shock proteins (HSP) of 60, 70, 90 kDa, and valosin-containing protein (VCP) of 92 kDa. The presence of anti-membrane antibodies was confirmed by immunofluorescence and immunoelectron microscopy. CONCLUSION: Overall, our data demonstrate that liver arginase, CK 8/18, HSP 60, HSP 70, HSP 90, and VCP represent potential candidate targets on liver membrane for autoantibodies in AIH-1.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/isolamento & purificação , Membrana Celular/imunologia , Hepatite Autoimune/imunologia , Proteínas de Membrana/isolamento & purificação , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Autoantígenos/imunologia , Criança , Feminino , Hepatite Autoimune/diagnóstico , Hepatócitos/imunologia , Humanos , Immunoblotting , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Proteômica
19.
Ann N Y Acad Sci ; 1109: 345-57, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17785324

RESUMO

De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so-called atypical anti-liver/kidney microsome antibodies (LKMA) with an unusual liver/kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti-LKMA targets by proteomic tool. This proteomic approach consisted of (a) two-dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat kidney, followed by (b) two-dimensional immunoblotting with sera of patients with de novo AIH (n = 8, including 2 with anti-LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S-transferase (GST) families, and subunit beta1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.


Assuntos
Autoanticorpos/imunologia , Hepatite Autoimune/imunologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/imunologia , Proteômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Citosol/imunologia , Bases de Dados de Proteínas , Eletroforese em Gel Bidimensional , Feminino , Hepatite Autoimune/patologia , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade
20.
Clin Transplant ; 19(5): 591-9, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16146549

RESUMO

Cryptogenic cirrhosis (CC) is diagnosed in 5-30% of cirrhotic patients overall and 7% of patients who undergo liver transplantation for cirrhosis. In our series of patients transplanted for CC, pre-transplant clinical and histological data and the post-transplant course were reexamined in an attempt to identify the aetiology. Among the 881 patients transplanted in our centre between 1987 and 2000, 28 patients with a median age of 46 yr (range: 18-69) at transplantation were initially classified as having CC. Two patients were excluded because of intense ischaemic lesions caused by chemoembolization prevented histological analysis of the native liver (n = 1) and because of cryptic HBV infection (n = 1). Among the remaining 26 patients, four groups were individualized: (i) patients with chronic inflammatory liver disease with autoimmune features (n = 14, 54%); (ii) patients with features suggestive of non-alcoholic fatty liver disease (n = 3, 11.5%); (iii); patients with incomplete septal cirrhosis (ISC) and vascular liver disease (n = 3), and (iv) patients with unresolved CC (n = 6, 23%). In the autoimmune liver disease group, the median International Autoimmune Hepatitis score was 12.5 (range: 11-19) after reevaluation and review of the post-transplantation course was helpful to confirm the diagnosis with the occurrence of active graft hepatitis in nine patients, with autoantibodies in five patients. The vascular group was characterized by lesions of obliterative portal venopathy and ISC in all native livers. Diagnosis of NAFLD was based on the clinical background of obesity and/or type 2 diabetes and the presence of steatosis or steatohepatitis in native livers and graft biopsies. A definite aetiological diagnosis can be achieved in the majority of patients initially diagnosed with CC. Autoimmune liver disease emerged as the main aetiology (14 of 26 patients, 54%) and frequently recurred on the grafted liver (nine cases). In all cases a precise diagnosis is obviously of practical interest for better management of post-transplant survey and treatment.


Assuntos
Cirrose Hepática/patologia , Transplante de Fígado , Fígado/patologia , Adolescente , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Fígado Gorduroso/cirurgia , Feminino , Seguimentos , Hepatite Autoimune/complicações , Hepatite Autoimune/patologia , Hepatite Autoimune/cirurgia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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