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1.
J Neurovirol ; 25(6): 825-836, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31332697

RESUMO

Treatment-emergent depression is a common complication in patients with chronic hepatitis C virus (HCV) infection undergoing antiviral combination therapy with IFN-α and ribavirin. It has recently been shown that changes in A-to-I RNA editing rates are associated with various pathologies such as inflammatory disorders, depression and suicide. Interestingly, IFN-α induces gene expression of the RNA editing enzyme ADAR1-1 (ADAR1a-p150) and alters overall RNA editing activity. In this study, we took advantage of the high prevalence of pharmacologically induced depression in patients treated with IFN-α and ribavirin to test the interest of RNA editing-related biomarkers in white blood cells of patients. In this 16-week longitudinal study, a small cohort of patients was clinically evaluated using standard assessment methods prior to and during antiviral therapy and blood samples were collected to analyse RNA editing modifications. A-I RNA editing activity on the phosphodiesterase 8A (PDE8A) gene, a previously identified RNA editing hotspot in the context of lupus erythematosus, was quantified by using an ultra-deep next-generation sequencing approach. We also monitored gene expression levels of the ADAR enzymes and the PDE8A gene during treatment by qPCR. As expected, psychiatric evaluation could track treatment-emergent depression, which occurred in 30% of HCV patients. We show that PDE8A RNA editing is increased in all patients following interferon treatment, but differently in 30% of patients. This effect was mimicked in a cellular model using SHSY-5Y neuroblastoma cells. By combining the data of A-I RNA editing and gene expression, we generated an algorithm that allowed discrimination between the group of patients who developed a treatment-emergent depression and those who did not. The current model of drug-induced depression identified A-I RNA editing biomarkers as useful tools for the identification of individuals at risk of developing depression in an objective, quantifiable biological blood test.


Assuntos
Antivirais/efeitos adversos , Biomarcadores/sangue , Depressão/sangue , Depressão/induzido quimicamente , Hepatite C Crônica/tratamento farmacológico , Edição de RNA/efeitos dos fármacos , 3',5'-AMP Cíclico Fosfodiesterases/sangue , 3',5'-AMP Cíclico Fosfodiesterases/genética , Adenosina Desaminase/sangue , Adenosina Desaminase/genética , Adulto , Idoso , Feminino , Hepacivirus , Humanos , Interferon-alfa/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Edição de RNA/fisiologia , Proteínas Recombinantes/efeitos adversos , Ribavirina/efeitos adversos
2.
J Clin Virol ; 103: 63-70, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29656087

RESUMO

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is emerging but its circulation between humans and the environment remains misunderstood. HEV ORF2 gene encodes the capsid playing a key role in viral interactions with surfaces, ORF3 products are involved in the viral cycle. Our aim was to study the molecular characteristics of ORF2 and ORF3 which could favor HEV fitness in patients and the environment. STUDY DESIGN: Samples from 69 patients with hepatitis (blood/stools), 20 urban wastewaters, 20 effluents of a pig slaughterhouse, 22 farm pigs (stools), 20 wild boars (liver/stools) were collected in North-Eastern France. HEV strains were analyzed by direct sequencing within the ORF2 M region, of ORF2/ORF3, for phylogeny and physicochemical prediction and for ORF2 by ultra-deep sequencing. RESULTS: The results showed frequent HEV-positive samples: 9.1% of the patient bloods, 23.1% of their stools; 25.0% of wastewaters, 75.0% for the slaughterhouse, 10.0% of the boar livers, 5.3% of their stools. The strains were classified as HEV genotype 3. In ORF2, HEV highlighted one homogeneous major viral variant within quasispecies and a decrease in predicted antigenicity for two minor mutations (D442G, V402A). A cysteine signature at position 81 in ORF3 was observed in the boars. CONCLUSIONS: HEV RNA genotype 3 was detected in patients and in animals, in a slaughterhouse effluent and in wastewater. Moreover, the low variability of amino acids in the ORF2 M region and molecular features in ORF2 and ORF3 suggested that HEV strains could be advantageous for key properties.


Assuntos
Fezes/virologia , Genótipo , Vírus da Hepatite E/classificação , Hepatite E/epidemiologia , Hepatite E/veterinária , Esgotos/virologia , Doenças dos Suínos/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , França/epidemiologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Análise de Sequência de DNA , Sus scrofa , Suínos , Doenças dos Suínos/epidemiologia , Proteínas Virais/genética
3.
Eur J Radiol ; 85(1): 103-112, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26724654

RESUMO

PURPOSE: The first aim was to compare Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, modified Response Evaluation Criteria in Solid Tumor (mRECIST), Choi and European Association for the Study of the Liver (EASL) evaluations to assess the response to sorafenib for hepatocellular carcinoma (HCC). The second aim was to describe the evolution of HCC and to identify whether some imaging features are predictive of the absence of response. MATERIALS AND METHODS: This retrospective study included 60 patients with advanced HCC treated with sorafenib. Patients must have undergone a scan prior to treatment to identify the number of lesions, size, enhancement and endoportal invasions, and repeat scans thereafter. Computed tomography (CT) scans were analyzed using RECIST 1.1, mRECIST, Choi and EASL criteria. Overall survival was analyzed. RESULTS: The median overall survival was 10.5 months. On the first CT reevaluation, the sorafenib response rates were 20%, 5%, 7% and 3% according to Choi, EASL, mRECIST and RECIST 1.1. The responders based on Choi exhibited significantly better overall survival compared with non-responders (20.4 months; hazard ratio (HR) 0.042, 95% confidence interval (CI): 0.186-0.94, p=0.035). A modification of imaging findings was observed in 48.3% of patients, and necrosis was present in 44.1% of patients. CONCLUSION: This study found a significant difference between Choi versus RECIST 1.1, mRECIST and EASL when evaluating the response to sorafenib in HCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sorafenibe , Análise de Sobrevida , Resultado do Tratamento
4.
J Viral Hepat ; 23(5): 387-98, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26742490

RESUMO

For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs 'a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.


Assuntos
Variação Antigênica , Antivirais/uso terapêutico , Variação Genética , Antígenos de Superfície da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Adulto , Idoso , Substituição de Aminoácidos , Animais , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Proteínas Mutantes/imunologia , Análise de Sequência de DNA
5.
J Viral Hepat ; 22(12): 1002-10, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26216230

RESUMO

Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.


Assuntos
Algoritmos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Prolina/análogos & derivados , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Polietilenoglicóis/uso terapêutico , Prolina/uso terapêutico , Distribuição Aleatória , Ribavirina/uso terapêutico , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
6.
CPT Pharmacometrics Syst Pharmacol ; 4(1): e00008, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26225222

RESUMO

Hézode et al. recently reported the frequent occurrence of anemia and thrombocytopenia in the ANRS-CO20-CUPIC cohort of hepatitis C virus (HCV) cirrhotic experienced patients treated with pegylated-interferon (Peg-IFN), ribavirin (RBV), and telaprevir or boceprevir.1,2 Using frequent measurements of serum drug concentrations, hemoglobin, and platelet concentrations obtained in 15 patients of this cohort, we show how an on-treatment model-based approach could be used to individualize dose regimen and avoid the occurrence of RBV-induced anemia and Peg-IFN-induced thrombocytopenia.

7.
Aliment Pharmacol Ther ; 40(1): 3-15, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24815622

RESUMO

BACKGROUND: Extraintestinal manifestations are frequent in inflammatory bowel diseases (IBD). Most studies published so far focused on viral hepatitis and liver toxicity of IBD-related drugs. AIM: To conduct a systematic review of hepatobiliary manifestations associated with IBD. We excluded viral hepatitis and liver toxicity of IBD-related drugs. METHODS: Studies were identified through the electronic database of MEDLINE, EMBASE and the annual meetings of Digestive Disease Week, the American College of Gastroenterology, the United European Gastroenterology Week and the European Crohn's and Colitis Organization. RESULTS: One hundred and forty six articles were included in this systematic review. Cholelithiasis is more frequent in Crohn's disease (CD) than in general population. Prevalence of cholelithiasis in CD ranged from 11% to 34%, whereas it ranges from 5.5% to 15% in non-IBD patients. PSC is more frequent in UC than in CD. Prevalence of PSC ranges from 0.76% to 5.4% in UC and from 1.2% to 3.4% in CD. There is a male predominance when PSC is associated with UC, with a male/female ratio ranging from 65/35 to 70/30. No conclusion can be made on a possible increased risk of gall-bladder carcinoma. Mean prevalence of fatty liver is 23% (range, 1.5-55%). Hepatic amyloidosis occurs in less than 1% of IBD. Liver abscess is encountered mainly in CD. Portal vein thrombosis occurs in 39% to 45% of IBD patients undergoing proctocolectomy. CONCLUSIONS: Hepatobiliary manifestations associated with inflammatory bowel diseases are frequent and probably underdiagnosed.


Assuntos
Doenças Biliares/epidemiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Hepatopatias/epidemiologia , Doenças Biliares/etiologia , Doenças Biliares/fisiopatologia , Feminino , Humanos , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Masculino , Prevalência , Risco , Fatores Sexuais
8.
Int J Clin Pract ; 68(5): 609-17, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24283303

RESUMO

BACKGROUND: GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma [HCC] and Of its treatment with sorafeNib) is a global, prospective, non-interventional study undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real-life practice, including Child-Pugh B patients who were excluded from clinical trials. METHODS: Patients with unresectable HCC, for whom the decision to treat with sorafenib, based on the approved label and prescribing guidelines, had been taken by their physician, were eligible for inclusion. Demographic data and disease/medical history were recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at follow-up visits. The second interim analysis was undertaken when ~1500 treated patients were followed up for ≥ 4 months. RESULTS: Of the 1571 patients evaluable for safety, 61% had Child-Pugh A status and 23% Child-Pugh B. The majority of patients (74%) received the approved 800 mg initial sorafenib dose, regardless of Child-Pugh status; however, median duration of therapy was shorter in Child-Pugh B patients. The majority of drug-related AEs were grade 1 or 2, and the most commonly reported were consistent with previous reports. The incidence and nature of drug-related AEs were broadly similar across Child-Pugh, Barcelona Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the overall population. CONCLUSIONS: Consistent with the first interim analysis, overall safety profile and dosing strategy are similar across Child-Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Estudos Prospectivos , Sorafenibe , Adulto Jovem
9.
Clin Exp Allergy ; 44(5): 756-64, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24128045

RESUMO

BACKGROUND: We evaluated the value of skin tests and the efficacy of a 12-step desensitization protocol to pegylated interferon (IFN) in patients with generalized drug eruptions due to IFNs. METHODS: A retrospective study (1998-2009) was followed by a cross-sectional clinical study conducted prospectively (2009-2011). All patients received a dermatological clinical examination and skin tests. Twelve-step IFN desensitization was proposed for patient with active hepatitis C and no alternative therapy. RESULTS: Twenty-six patients (13 males, mean age, 53.5 years) had generalized reactions to IFNs; 21 were treated with IFN-α and 5 with IFN-ß. Moreover, 21 patients had skin tests. Intradermal tests (IDTs) were positive after an average of 72 h. Cross-reactivity between peg-IFN-α2a and peg-IFN-α2b was observed in 5/10 cases in the prospective study. In 16 of 26 cases, IFN treatment was stopped. In 8 of 16 cases of diffuse eczematous drug eruption, treatment was continued. The corticosteroid and antihistamine were sufficient in 4/8 cases. In three other cases, topical tacrolimus was highly effective. In 3 of 16 cases in which treatment were stopped, patients underwent the early resumption of peg-IFN-α. These three patients had positive tests with peg-IFN-α2a and peg-IFN-α2b and successfully completed the tolerance induction protocol for peg-IFN-α2b. Tolerance induction involved a weekly dose of peg-IFN and a gradual increase in the recovery of an antiviral C. Clinical tolerance was excellent, and the patients' viral load C became negative. CONCLUSIONS: Our study demonstrates the benefit of allergy testing in cases of generalized drug reactions to IFN, cross-reactivities in a single class of IFNs and the importance of delayed IDT reading. We report for the first time the effectiveness of 12-step desensitization with peg-IFN.


Assuntos
Dessensibilização Imunológica , Toxidermias/diagnóstico , Toxidermias/terapia , Interferons/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Estudos Transversais , Dessensibilização Imunológica/métodos , Feminino , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/patologia , Resultado do Tratamento
10.
Aliment Pharmacol Ther ; 38(1): 16-27, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23710734

RESUMO

BACKGROUND: Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1. AIM: To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R. METHODS: Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7-9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned. RESULTS: Most patients (63-71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86-90%. In contrast, patients who adhered to <80% of their assigned treatment duration achieved SVR rates of 8-32% (P < 0.0001), particularly low in patients who failed previous therapy (SVR = 8-15%). Different rates of adherence (<60% to >80%) to the t.d.s. dosing interval (7-9 h) with BOC did not influence the SVR rates (SVR = 60-83%) with the exception of patients who failed previous treatment and adhered to <60% of the t.d.s. dosing interval with BOC (SVR = 48-50%; P = 0.005). CONCLUSIONS: The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t.d.s. dosing interval with boceprevir. Adherence to >60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adesão à Medicação , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Ribavirina/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , RNA Viral/genética , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral
11.
Int J Clin Pract ; 66(7): 675-83, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22698419

RESUMO

AIMS: Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non-interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real-life practice conditions, particularly Child-Pugh B patients, who were not well represented in clinical trials. METHODS: Treatment decisions are determined by each physician according to local prescribing guidelines and clinical practice. Patients with uHCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Demographic data and medical and disease history are recorded at entry. Sorafenib dosing and adverse events (AEs) are collected throughout the study. RESULTS: From January 2009 to April 2011, >3000 patients from 39 countries were enrolled. The prespecified first interim analysis was conducted when the initial approximately 500 treated patients had been followed up for ≥4 months; 479 were valid for safety evaluation. Preplanned subgroup analyses indicate differences in patient characteristics, disease aetiology and previous treatments by region. Variation in sorafenib dosing by specialty are also observed; Child-Pugh status did not appear to influence the starting dose of sorafenib. The type and incidence of AEs was consistent with findings from previous clinical studies. AE profiles were comparable between Child-Pugh subgroups. DISCUSSION: The GIDEON study is generating a large, robust database from a broad population of patients with uHCC. First interim analyses have shown global and regional differences in patient characteristics, disease aetiology and practice patterns. Subsequent planned analyses will allow further evaluation of early trends.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Tomada de Decisões , Neoplasias Hepáticas/tratamento farmacológico , Prática Profissional , Piridinas/uso terapêutico , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Niacinamida/análogos & derivados , Compostos de Fenilureia , Ensaios Clínicos Controlados Aleatórios como Assunto , Características de Residência , Sorafenibe , Especialização/estatística & dados numéricos
12.
Rev Med Interne ; 32(6): 341-6, 2011 Jun.
Artigo em Francês | MEDLINE | ID: mdl-21269740

RESUMO

PURPOSE: Wilson's disease (WD) is an inherited disorder of copper metabolism, characterized by the accumulation of copper in the body due to defective biliary copper excretion by hepatocytes. We report a series of 19 patients with WD. PATIENTS AND METHODS: This is a retrospective and descriptive case series of patients with WD followed in two hospitals of North East of France. RESULTS: Eight men and 11 women were studied. Median follow-up time was 16 years, median age at diagnosis was 18 years (range: 5-71 years). Median age at first symptom was 16 years. In addition to four cases diagnosed by familial screening, clinical manifestations at diagnosis were fatigue (n=5), jaundice (n=5), bleeding (n=1), abnormal movement disorders (n=2) and fortuitous (n=2). Cirrhosis was identified in 14 patients, neurological involvement occurred in seven patients and four patients presented with psychiatric disorders. d-penicillamine was the first treatment in 18 patients, discontinued for severe adverse events in seven patients. Trientine or zinc salts were then prescribed. Medical treatment was successful in 13 patients, but five patients underwent liver transplantation. Haemochromatosis was associated in one case, and one patient developed cholangiocarcinoma. CONCLUSION: WD is severe. Medical treatment allows disease control if it is correctly observed. Conversely, worsening with irreversible damage can occur if the treatment is discontinued.


Assuntos
Degeneração Hepatolenticular , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Gastroenterol Clin Biol ; 33(12): 1082-93, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19896313

RESUMO

The risk of viral B and C hepatitis has long been considered to be increased in patients with inflammatory bowel disease (IBD). Blood transfusion and surgery have been identified as the two main risk factors, suggesting nosocomial transmission could be involved. However, recent epidemiologic surveys have found that prevalence in IBD patients is similar to or even lower than that in the general population. Part of the explanation of these recent data may lie in the application of protective measures against viral infection (hepatitis B virus [HBV] vaccination and hepatitis C virus [HCV]-free blood transfusions). Sometimes fatal viral reactivations have been reported in patients on immunosuppressive therapy. Two periods can be distinguished: a) during therapy, a rise in viremia associated with a decrease of immune-mediated hepatic lesions; b) after cessation of therapy, an immune rebound with a destruction of virus-infected hepatocytes. For HBV, preemptive strategy consisting of an antiviral analog is efficient in chronic HBs antigen carriers. For HCV, the impact of immunosuppressive drugs on the natural history is unclear. Most studies report improved comfort although no biopsies were performed before and after immunosuppressive treatment. Physicians managing IBD patients should be aware of the need for screening and institute preventive measures against B and C hepatitis.


Assuntos
Hepatite B/etiologia , Hepatite C/etiologia , Doenças Inflamatórias Intestinais/complicações , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Prevalência
17.
Gastroenterol Clin Biol ; 32(3 Pt 2): S109-16, 2008 Mar.
Artigo em Francês | MEDLINE | ID: mdl-18675180

RESUMO

After a treatment by peginterferon alpha and ribavirin, the percentages of non response and relapse are approximatively 33 and 18 % respectively. These treatment failures may be due either to viral resistance or to an insufficient treatment. The prevention of treatment failure is based on a good knowledge of the predictive factors of failure before and during the treatment. Among the patients who did not respond to interferon alpha and ribavirin, a new treatment with peginterferon alpha-2b and ribavirin makes it possible to obtain 45 % of sustained virological response (SVR) among the relapsers and 17 % of SVR among the non responders. Among the patients who did not respond to peginterferon alpha and ribavirin, a new treatment with peginterferon alpha-2b and ribavirin makes it possible to obtain 36 % of SVR among the relapsers and only 4 % of SVR among the non responders. New therapeutic strategies are necessary for the non responders. Until now no new therapeutic strategy allowed a significant benefit in term of SVR. Protease inhibitors are currently tested in non responders but there are some concerns about the risk of selection of multi-resistant strains.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Farmacorresistência Viral , Quimioterapia Combinada , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes , Ribavirina/uso terapêutico , Falha de Tratamento
18.
Aliment Pharmacol Ther ; 28(8): 984-93, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18657132

RESUMO

BACKGROUND: The interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity, remains unexplored. AIM: To underline the interaction of ribavirin, an inosine monophosphate dehydrogenase inhibitor, with azathioprine metabolism, potentially leading to myelotoxicity. METHODS: The medical records of eight patients who developed severe pancytopenia following concomitant use of azathioprine and ribavirin were retrospectively reviewed. RESULTS: Bone marrow suppression reached nadir after a mean interval of 4.6 +/- 1.6 weeks following HCV therapy initiation in seven patients. At the time of pancytopenia, the mean platelet count was 69.75 +/- 82.8 x 10(-3)/mm(3), mean haemoglobin level 7.75 +/- 1.3 g/dL and mean neutrophil count 0.45 +/- 0.26 x 10(-3)/mm(3). All patients had normal thiopurine methyltransferase genotype. In two patients, a prospective monitoring of azathioprine metabolites was available. Myelotoxicity was accompanied by elevated total methylated metabolite levels (16,500 and 15,000 pmol/8 x 10(8) erythrocytes) with a concomitant decrease in 6-tioguanine nucleotide levels; 1 month after azathioprine, pegylated interferon alfa and ribavirin were discontinued and full blood count returned to normal in both patients. No haematological toxicity occurred after the reintroduction of peginterferon plus ribarivin or azathioprine alone in eight patients. CONCLUSION: Collectively, the benefit/risk ratio favours avoidance of inosine monophosphate dehydrogenase inhibitors in purine analogue-treated patients with normal thiopurine methyltransferase activity, a situation frequently encountered in clinical practice.


Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pancitopenia/induzido quimicamente , Adulto , Azatioprina/efeitos adversos , Interações Medicamentosas , Feminino , Hepatite C Crônica/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Masculino , Pessoa de Meia-Idade , Pancitopenia/sangue , Pancitopenia/genética , Contagem de Plaquetas , Estudos Retrospectivos , Ribavirina/efeitos adversos , Fatores de Risco
19.
Gastroenterol Clin Biol ; 32(1 Pt 2): S50-5, 2008 Jan.
Artigo em Francês | MEDLINE | ID: mdl-18662610

RESUMO

Nucleos(t)ide analogues are very efficient in the treatment of chronic hepatitis B. In the HBe antigen positive patients, the HBe seroconversion rates range from 12 to 22% after one year of treatment. When HBe seroconversion occure, it is possible to stop the treatment with analogue but only in non cirrhotic patients. If the treatment with analogue is continued for at least 6 months after confirmed HBeAg seroconversion, the HBe seroconversion is durable in 70-90% of patients. The follow up should be done during years. Stopping the treatment is more problematic in HBe antigen negative patients. A virological relapse occur in 44 to 80% of cases and a biochemical relapse occur in 30 to 70% of cases. Stopping the treatment with an analogue in this population should be considered only in a prospective study with careful monitoring and with a long term follow up.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , DNA Viral/análise , Antígenos da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Recidiva
20.
Eur J Cancer ; 44(4): 528-38, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18242076

RESUMO

The FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P=.68), respectively. Multivariate analysis identified four independent prognostic factors for survival: alpha-fetoprotein (AFP)>400ng/mL (P=.008), abdominal pain (P=.011), hepatomegaly (P=.023) and Child-Pugh score (P=.032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P=.70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P=.58). In this subgroup, two prognostic factors were statistically significant for survival: AFP>400ng/mL (P=.004) and Spitzer Index (P=.013) as shown by multivariable analysis. In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/terapia , Tamoxifeno/uso terapêutico , Carcinoma Hepatocelular/complicações , Terapia Combinada , Feminino , Humanos , Infusões Intra-Arteriais , Tempo de Internação , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento
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