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2.
Front Immunol ; 9: 2400, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386345

RESUMO

Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.

3.
Pediatr Rheumatol Online J ; 16(1): 38, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925381

RESUMO

BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare pediatric autoimmune disease with broad variations of the individual course. Data on the optimal management are mostly lacking. Currently treatment decisions are often based on experts' opinions. In order to develop consensus-based treatment strategies for JDM in Germany a survey was pursued to analyze the current clinical practice. METHODS: An online survey addressing all members of the Society for Pediatric Rheumatology (GKJR) in Germany and Austria and pediatric neurologists with expertise in JDM was performed in February/March of 2016. The questionnaire consisted of 5 case scenarios including diagnostic criteria, treatment of moderate, severe and refractory JDM, using either multiple choice or a 5-point Likert scale. Basic descriptive statistics were used to analyze the findings. RESULTS: The survey was completed by 60 pediatric rheumatologists and 7 pediatric neurologists experienced in the management of JDM. Typical findings allowing a diagnosis were considered to be: typical skin changes, proximal muscle weakness, MRI findings, elevated muscle enzymes, nailfold capillary changes, presence of calcinosis and muscle biopsy. Regarding induction treatment of moderate/severe JDM: 59%/74% opted for intermittent intravenous methylprednisolone (IVMP) pulse therapy, and 21%/40% for conventional high-dose oral glucocorticoids. Methotrexate (MTX) was the preferred disease-modifying conventional anti-rheumatic drug (cDMARD) for moderate and severe JDM. Regarding the management of refractory moderate or severe JDM, intravenous immune globulins, mycophenolate mofetil and rituximab were preferred treatment options. CONCLUSION: There is consensus about the diagnosis of JDM strongly supported by classic clinical and MRI findings. There is great variety in the treatment of JDM in Germany regarding both induction and maintenance therapy. The development of consensus-based treatment strategies for JDM based on harmonization of current clinical practice is essential in order to allow comparative effectiveness research in the future.


Assuntos
Dermatomiosite/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Antirreumáticos/uso terapêutico , Áustria , Criança , Consenso , Dermatomiosite/diagnóstico , Alemanha , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas , Neurologistas , Reumatologistas , Inquéritos e Questionários
4.
Pediatr Rheumatol Online J ; 16(1): 40, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29940960

RESUMO

BACKGROUND: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM. METHODS: The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements. RESULTS: Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-to-target strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease. CONCLUSION: Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM.


Assuntos
Dermatomiosite/tratamento farmacológico , Antirreumáticos/uso terapêutico , Áustria , Criança , Consenso , Dermatomiosite/diagnóstico , Gerenciamento Clínico , Alemanha , Glucocorticoides/uso terapêutico , Humanos , Inquéritos e Questionários
5.
Rheumatology (Oxford) ; 56(9): 1597-1606, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28859329

RESUMO

Objectives: The aim was to analyse factors influencing the individual colchicine dose in children with FMF, to evaluate the impact of dose adjustment on the clinical course and inflammation and to identify clinical parameters and biomarkers that predict dose increase in the near future. Methods: Data from 409 paediatric FMF patients (4566 visits) derived from the national auto-inflammatory diseases registry were analysed. Serum concentrations of S100 molecules were determined by ELISA. Results: The age-dependent colchicine dose is influenced by the present genotype. The body surface area is the anthropometric parameter that correlates best with the applied dosages. Colchicine introduction and dose increase lead to significant reduction of clinical symptoms and inflammation. During established colchicine therapy, an increase of one single biomarker increases the likelihood of a dose increment in the next 12 months with a factor of 1.62-1.94. A combination of biomarkers including S100 molecules increases this odds ratio up to 4.66 when analysing all patients and up to 7.27 when analysing patients with a high risk of severe disease. Conclusion: Colchicine therapy is currently guided mainly by the occurrence of clinical symptoms and serological inflammation. Other factors, such as the genotype, the body surface area and biomarkers, will help to manage colchicine therapy in a more individualized fashion. The additional analysis of S100 molecules as sensitive biomarkers will help to identify patients at risk for dose increases in the near future.


Assuntos
Colchicina/administração & dosagem , Febre Familiar do Mediterrâneo/tratamento farmacológico , Adolescente , Fatores Etários , Antropometria/métodos , Biomarcadores/sangue , Superfície Corporal , Criança , Pré-Escolar , Colchicina/efeitos adversos , Colchicina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Feminino , Genótipo , Humanos , Masculino , Prognóstico , Sistema de Registros , Proteínas S100/sangue , Índice de Gravidade de Doença
6.
Eur J Pediatr ; 176(10): 1319-1327, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28808789

RESUMO

The number of children without a diagnosis in pediatric palliative home care and the process of decision-making in these children are widely unknown. The study was conducted as single-center retrospective cohort study. Between January 2013 and September 2016, 198 children and young adults were cared for; 27 (13.6%) of these were without a clear diagnosis at the start of pediatric palliative home care. A definite diagnosis was ultimately achieved in three children. Median age was 7 years (0-25), duration of care 569 days (2-2638), and number of home visits 7.5 (2-46). Most patients are still alive (19; 70.4%). Median number of drugs administered was eight (range 2-19); antiepileptics were given most frequently. Despite the lack of a clear diagnosis (and thus prognosis), 13 (48.1%) parents faced with their critically ill and clinically deteriorating children decided in favor of a DNAR order. Comparing this with 15 brain-injured children, signs, symptoms, and supportive needs were similar in both groups. CONCLUSION: Children without a clear diagnosis are relatively common in pediatric palliative care and have-like all other patients-the right to receive optimized and symptom-adapted palliative care. Parents are less likely to choose treatment limitation for children who lack a definitive diagnosis. What is Known: • A clear diagnosis is usually considered important for best-practice pediatric palliative care (PPC) including advanced care planning (ACP). • Timely initiation of pediatric palliative care (PPC) is highly recommended in children with life-limiting conditions. What is New: • SWAN (syndrome without a name) children show similar signs and symptoms (mostly neurological) and have similar supportive needs as brain-injured children. • Defining treatment limitations in advance care planning is more difficult for parents of SWAN compared to brain-injured children.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Cuidados Paliativos , Adolescente , Planejamento Antecipado de Cuidados/ética , Criança , Pré-Escolar , Tomada de Decisão Clínica , Tomada de Decisões , Diagnóstico Tardio/ética , Diagnóstico Tardio/psicologia , Feminino , Alemanha , Humanos , Lactente , Recém-Nascido , Masculino , Cuidados Paliativos/ética , Cuidados Paliativos/métodos , Cuidados Paliativos/psicologia , Cuidados Paliativos/estatística & dados numéricos , Pais/psicologia , Relações Profissional-Família , Estudos Retrospectivos , Síndrome , Assistência Terminal/ética , Assistência Terminal/métodos , Assistência Terminal/psicologia , Suspensão de Tratamento/ética , Adulto Jovem
7.
Arthritis Res Ther ; 19(1): 147, 2017 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-28666454

RESUMO

BACKGROUND: Valid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring. METHODS: A 24-week observational study in polyarticular JIA patients newly starting treatment with methotrexate or an approved biologic was performed in three centers. Patients were evaluated clinically, by gray-scale ultrasonography (GSUS), power-Doppler ultrasonography (PDUS) and FOI at baseline, week 12 and week 24. RESULTS: Of 37 patients enrolled, 24 patients started methotrexate and 13 patients a biologic for the first time (etanercept n = 11, adalimumab and tocilizumab n = 1 each). Mean JADAS 10 decreased significantly from 17.7 at baseline to 12.2 and 7.2 at week 12 and 24 respectively. PedACR 30/50/70/100 response rates at week 24 were 85%/73%/50%/27%. The total number of clinically active joints in hand and fingers at baseline/week 12/week 24 was 262 (23.6%)/162 (16.4%)/162 (9.0%). By GSUS, at baseline/week 12/week 24, 192 (19.4%)/135 (16.1%)/83 (11.5%) joints showed effusions and 186 (18.8%)/107 (12.7%)/69 (9.6%) showed synovial thickening, and by PDUS 68 (6.9%)/15 (1.8%)/36 (5%) joints showed hyperperfusion. Any sign of arthritis was detected by US in a total of 243 joints (24.5%) at baseline, 161 joints (19.2%) at week 12 and 123 joints (17%) at week 24. By FOI at baseline/week 12/week 24, 430 (38.7%)/280 (29.2%)/215 (27.6%) showed a signal enhancement in at least one phase. Summarizing all three points of time, the highest numbers of signals were detected by FOI with 32% of joints, especially in phase 2, while by US 20.7% and by clinical examination 17.5% of joints were active. A high number of joints (21.1%) had FOI signals but were inactive by clinical examination. A total 20.1% of joints with signals in FOI did not show effusion, synovial thickening or hyperperfusion by US. Because of the high number of negative results, specificity of FOI compared with clinical examination/US/PD was high (84-95%), and sensitivity was only moderate. CONCLUSION: FOI and US could detect clinical but also subclinical inflammation. FOI detected subclinical inflammation to a higher extent than US. Improvement upon treatment with either methotrexate or a biologic can be visualized by FOI and US. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00011579 . Registered 10 January 2017.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/diagnóstico por imagem , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Imagem Óptica/métodos , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Doenças Musculoesqueléticas/diagnóstico por imagem , Doenças Musculoesqueléticas/tratamento farmacológico , Resultado do Tratamento , Ultrassonografia/métodos
9.
Clin Exp Rheumatol ; 34(6): 1113-1120, 2016 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27749226

RESUMO

OBJECTIVES: While tumour necrosis factor (TNF)-α-inhibitor treatment improved outcome of juvenile idiopathic arthritis (JIA) management markedly, concerns have been raised about an association of TNF-α-inhibitor treatment and an increased risk for malignancies especially lymphoma. METHODS: Cases of suspected malignancies documented in the German Biker Registry are reviewed in detail. RESULTS: Until Dec 31, 2015, 3695 JIA patients were prospectively followed with a total of more than 13,198 observation years. 12 cases of suspected malignancies, including 7 lymphoid neoplasms, have been reported in patients treated with methotrexate (MTX) , and /or TNF-α inhibitors. 11 patients had received MTX, two received cyclosporine A, single patients received sulfasalazine, azathioprine or leflunomide. 10 patients were exposed to biologics, 9 etanercept, two adalimumab, one infliximab and one case was consecutively treated with adalimumab, etanercept, infliximab and abatacept. A case of mild myelodysplasia, in which the patient recovered spontaneously, a case of lymphoproliferation without clonality and a case of cervical dysplasia were treated as suspected, but not confirmed malignancies. Cases in which a malignant disease was confirmed included two cases of Hodgkin's lymphoma, one case of non-Hodgkin's lymphoma, two cases of acute lymphatic leukaemia (ALL) and one patient with lymphoproliferative disorder, who recovered after discontinuation of immunosuppressive therapy. Single confirmed cases of thyroid carcinoma, yolk sac carcinoma and anaplastic ependymoma have also been described. One patient not exposed to biologics died of ALL, all other patients recovered. CONCLUSIONS: In this large cohort of JIA patients, the occurrence of malignancies was higher than in the general population. Whether JIA patients had an increased risk for malignancies, either through their rheumatic disease, or through treatment remains in debate. Treatment with etanercept seems not to further increase the malignancy risk. Long-term observation of JIA patients treated with TNF-α inhibitors into adulthood remains an important task.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Linfoma/induzido quimicamente , Linfoma/epidemiologia , Adolescente , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Sistema de Registros , Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores
10.
Eur J Paediatr Neurol ; 20(6): 898-903, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27506815

RESUMO

BACKGROUND: Cannabis extracts have a wide therapeutic potential but in many countries they have not been approved for treatment in children so far. OBJECTIVE: We conducted an open, uncontrolled, retrospective study on the administration of dronabinol to determine the value, efficacy, and safety of cannabis-based medicines in the treatment of refractory spasticity in pediatric palliative care. DESIGN AND PARTICIPANTS: Sixteen children, adolescents and young adults having complex neurological conditions with spasticity (aged 1.3-26.6 years, median 12.7 years) were treated with dronabinol by our specialized pediatric palliative care team between 01.12.2010 and 30.04.2015 in a home-care setting. Therapeutic efficacy and side effects were closely monitored. RESULTS: Drops of the 2.5% oily tetrahydrocannabinol solution (dronabinol) were administered. A promising therapeutic effect was seen, mostly due to abolishment or marked improvement of severe, treatment resistant spasticity (n = 12). In two cases the effect could not be determined, two patients did not benefit. The median duration of treatment was 181 days (range 23-1429 days). Dosages to obtain a therapeutic effect varied from 0.08 to 1.0 mg/kg/d with a median of 0.33 mg/kg/d in patients with a documented therapeutic effect. When administered as an escalating dosage scheme, side effects were rare and only consisted in vomiting and restlessness (one patient each). No serious and enduring side effects occurred even in young children and/or over a longer period of time. CONCLUSIONS: In the majority of pediatric palliative patients the treatment with dronabinol showed promising effects in treatment resistant spasticity.


Assuntos
Dronabinol/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Cuidados Paliativos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Dronabinol/administração & dosagem , Dronabinol/efeitos adversos , Resistência a Medicamentos , Feminino , Humanos , Lactente , Masculino , Espasticidade Muscular/etiologia , Tono Muscular/efeitos dos fármacos , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/tratamento farmacológico , Estudos Retrospectivos , Assistência Terminal , Resultado do Tratamento , Adulto Jovem
12.
Haematologica ; 100(9): 1189-98, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26113417

RESUMO

Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease.


Assuntos
Síndrome Linfoproliferativa Autoimune/imunologia , Códon sem Sentido , Proteína Ligante Fas/imunologia , Regulação da Expressão Gênica/imunologia , Receptores de Interleucina-12/imunologia , Transdução de Sinais/imunologia , Apoptose/genética , Apoptose/imunologia , Síndrome Linfoproliferativa Autoimune/genética , Caspase 10/genética , Caspase 10/imunologia , Caspase 8/genética , Caspase 8/imunologia , Linhagem Celular Transformada , Proteína Ligante Fas/genética , Feminino , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Masculino , Receptores de Interleucina-12/genética , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/imunologia , Transdução de Sinais/genética , Receptor fas/genética , Receptor fas/imunologia
13.
Clin Immunol ; 155(2): 231-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25451160

RESUMO

We report a novel type of mutation in the death ligand FasL that was associated with a severe phenotype of the autoimmune lymphoproliferative syndrome in two patients. A frameshift mutation in the intracellular domain led to complete loss of FasL expression. Cell death signaling via its receptor and reverse signaling via its intracellular domain were completely abrogated. In vitro lymphocyte proliferation induced by weak T cell receptor stimulation could be blocked and cell death was induced by engagement of FasL in T cells derived from healthy individuals and a heterozygous carrier, but not in FasL-deficient patient derived cells. Expression of genes implicated in lymphocyte proliferation and activation (CCND1, NFATc1, NF-κB1) was increased in FasL-deficient T cells and could not be downregulated by FasL engagement as in healthy cells. Our data thus suggest, that deficiency in FasL reverse signaling may contribute to the clinical lymphoproliferative phenotype of ALPS.


Assuntos
Síndrome Linfoproliferativa Autoimune/genética , Síndrome Linfoproliferativa Autoimune/metabolismo , Proteína Ligante Fas/genética , Homozigoto , Mutação , Receptores de Morte Celular/metabolismo , Transdução de Sinais , Apoptose , Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/imunologia , Pontos de Checagem do Ciclo Celular/genética , Criança , Pré-Escolar , Consanguinidade , Análise Mutacional de DNA , Proteína Ligante Fas/metabolismo , Feminino , Humanos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Imagem por Ressonância Magnética , Masculino , Linhagem , Fenótipo , Irmãos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
14.
Pediatr Blood Cancer ; 50(6): 1159-62, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17973315

RESUMO

BACKGROUND: Recently the UICC-TNM classification for differentiated thyroid cancer (DTC) was changed neglecting the special circumstances for children affected by the disease. While the 1997 TNM classification grouped tumours

Assuntos
Neoplasias da Glândula Tireoide/classificação , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Metástase Linfática , Masculino , Neoplasias da Glândula Tireoide/patologia
15.
J Pediatr Gastroenterol Nutr ; 43(3): 342-7, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16954957

RESUMO

OBJECTIVE: We evaluated the prevalence and clinical significance of hepatitis B virus (HBV) genotypes in children with chronic hepatitis B. METHODS: Hepatitis B virus genomes of 249 hepatitis Be antigen-positive chronic hepatitis B surface antigen carriers were genotyped based on restriction fragment length polymorphism. Genotypes were correlated with corresponding values for alanine aminotransferase levels, quantitative HBV DNA and histological findings. RESULTS: One hundred and sixty-two boys and 87 girls (mean age, 7.2 years) were studied. Ninety-six percent were attributed to HBV genotypes A (32.5%) or D (63.5%). The remaining were classified as genotypes B, C, E and F. There was no significant difference in both alanine aminotransferase levels and histological findings among different genotypes. However, there was a clear association between very high HBV DNA levels and individuals with genotype D (P = 0.006). Mean time follow-up of 3.6 years showed later anti-HBe seroconversion in patients with genotype D than in those with genotype A (58% vs 37%). CONCLUSIONS: Compared with children with genotype A, children with genotype D showed a significantly higher viral load. Inasmuch as a relationship exists between viral load and response to treatment in children infected through vertical transmission, children with genotype D have to be carefully monitored. Long-term studies are needed to determine whether these patients are at risk of a poorer outcome.


Assuntos
Genótipo , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Carga Viral , Adolescente , Alanina Transaminase/sangue , Biópsia , Criança , Pré-Escolar , DNA Viral/sangue , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/patologia , Hepatite B Crônica/transmissão , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa , Fígado/patologia , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
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