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1.
Rev Neurol (Paris) ; 177(8): 919-923, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34154827

RESUMO

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an advanced therapy for patients with Parkinson Disease (PD). Weight loss has been pointed out as an adverse event of LCIG infusion. AIMS OF THE STUDY: To compare weight changes between three groups of PD patients: patients treated with LCIG, patients within the first year of subthalamic deep brain stimulation (STN-DBS) and patients treated exclusively with oral treatment during 1 year of follow up. METHODS: Patients treated with LCIG were retrospectively matched by age, gender, disease duration and Hoehn and Yahr to patients undergoing STN-DBS and to patients both receiving the standard of care treatment and unwilling advanced therapies (SOC). Clinical features and weight were collected at baseline, and 12 months after introducing the treatment (LCIG and STN-DBS groups) or for one year of treatment (SOC). RESULTS: Eighteen patients were included in each group. They had no differences in clinical and demographic features, except for cognitive impairment. There was a mean weight (-5.8kg ±6.8) and BMI (-2.1kg/m2±2.6) reduction in the LCIG group after 12 months, while there was a slight weight loss in the SOC (-1.4kg ±3.1) and a weight increase in the STN-DBS group (5.4kg ±4.7). Differences of weight were statistically different between, LCIG and STN-DBS (P<0.001), LCIG and SOC (P=0.002) and STN-DBS and SOC (P<0.001). CONCLUSIONS: The study shows a significant weight reduction after starting LCIG infusion compared to the other groups. Weight loss should be closely monitored in patients treated with LCIG.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Antiparkinsonianos , Índice de Massa Corporal , Carbidopa , Estudos de Casos e Controles , Combinação de Medicamentos , Géis , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Estudos Retrospectivos , Padrão de Cuidado
2.
Mucosal Immunol ; 9(5): 1137-50, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26883727

RESUMO

The gut CD4(+) T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6-CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6(+)CD4(+) T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3(+) T regulatory (Treg) cells, specifically the CCR6(-) subset, was increased. The resulting imbalance in the Th17/CCR6(-) Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor-ß (TGF-ß) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6(+)CD4(+) T cells to the small intestine in treated HIV-1-infected individuals.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Quimiocina CCL20/imunologia , Infecções por HIV/imunologia , Receptores CCR6/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Antígenos CD4/genética , Antígenos CD4/imunologia , Estudos de Casos e Controles , Quimiocina CCL20/genética , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/imunologia , Enterócitos/efeitos dos fármacos , Enterócitos/imunologia , Enterócitos/virologia , Retroalimentação Fisiológica , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Intestino Delgado/virologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores CCR6/deficiência , Receptores CCR6/genética , Transdução de Sinais , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/virologia , Células Th17/efeitos dos fármacos , Células Th17/virologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia
3.
Am J Transplant ; 16(5): 1474-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26587971

RESUMO

There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new-generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir-based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty-five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated-interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti-HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New-generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation.


Assuntos
Antivirais/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Falência Renal Crônica/complicações , Transplante de Rim/efeitos adversos , Sofosbuvir/uso terapêutico , DNA Viral/genética , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hepacivirus/genética , Hepatite C/virologia , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Fatores de Risco , Segurança , Carga Viral
4.
Endoscopy ; 45(1): 35-41, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23136012

RESUMO

BACKGROUND AND STUDY AIMS: Uncovered self-expanding metal stents offer effective relief for colonic obstruction. The aim of this study was to determine the effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the treatment of benign colonic strictures. PATIENTS AND METHODS: All patients presenting with a symptomatic benign colonic stricture (occlusion or subocclusion) during a 6-year study period were treated with FCSEMSs. The stents were placed and removed 4 - 6 weeks later at one of 10 endoscopy centers. The efficacy of the stent (clinical and radiological signs of colonic decompression within 48 hours), technical success, stent retrieval, safety, and recurrence of symptoms were evaluated during follow-up. Univariate and multivariate analyses were performed to identify variables associated with clinical success, stent migration, and symptom recurrence. RESULTS: The study included 43 patients (24 men, 19 women; mean age 67.6 ± 10.4) with occlusive (n = 18) or subocclusive symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post-radiation (n = 1) strictures. Insertion was successful in all patients. Clinical success was obtained in 35 patients (81 %). Migration was observed in 27 patients (63 %). The median duration of stenting was 21 days (95 %CI 17.8 - 35.4 days). Multivariate analysis showed that stents more than 20 mm wide migrated significantly less often. Recurrence of obstructive symptoms was observed in 23 patients (53 %), irrespective of migration. No predictive factors for recurrence or clinical efficacy were found. CONCLUSIONS: FCSEMSs for treatment of symptomatic benign colonic strictures are safe and effective, despite a high rate of spontaneous migration.


Assuntos
Doenças do Colo/terapia , Endoscopia Gastrointestinal , Obstrução Intestinal/terapia , Stents , Idoso , Remoção de Dispositivo , Feminino , Migração de Corpo Estranho , Humanos , Masculino , Metais , Recidiva , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
5.
J Med Virol ; 83(3): 437-44, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21264864

RESUMO

New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (RBV; 800-1,200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum RBV and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age = 49, range 31-76) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/ml and the HCV genotypes were: G1 (n = 93) with 1a (n = 37) and 1b (n = 50), G4 (n = 20) and G5 (n = 2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR= 2.98, 95% CI: 1.15-7.72) and RBV of >2,200 ng/ml at week 12 (OR = 3.41, 95% CI: 1.31-8.90). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR = 6.82, 95% CI: 1.7-26.8), and HCV RNA <15 IU/ml at week 12 (OR = 25, 95% CI: 6.4-97.6). Thus a serum RBV concentration of >2,200 ng/ml was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.


Assuntos
Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Adulto , Idoso , Antivirais/sangue , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Interferon-alfa/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/uso terapêutico , Ribavirina/sangue , Resultado do Tratamento , Carga Viral
6.
HIV Med ; 10(7): 417-21, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19490173

RESUMO

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.


Assuntos
Alanina Transaminase/sangue , Fígado Gorduroso/enzimologia , Infecções por HIV/enzimologia , Hepatite C/enzimologia , Adulto , Biópsia , Contagem de Linfócito CD4 , Progressão da Doença , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Feminino , Fibrose , Genótipo , Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valores de Referência , Índice de Gravidade de Doença , Carga Viral , Adulto Jovem
8.
J Viral Hepat ; 16(7): 485-91, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19302337

RESUMO

Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients [11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-alpha) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-alpha production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-alpha than those of SVR, chronically infected or HD (P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14(+) CD16(+) monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-alpha in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance.


Assuntos
Hepatite C/imunologia , Interleucina-10/metabolismo , Monócitos/imunologia , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Citometria de Fluxo , Humanos , Subunidade p40 da Interleucina-12/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/química , Receptores CCR7/análise , Fator de Necrose Tumoral alfa/metabolismo
9.
J Viral Hepat ; 13(12): 811-20, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17109680

RESUMO

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN (P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose (P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2%vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Antivirais/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Polietilenoglicóis , Proteínas Recombinantes , Ribavirina/efeitos adversos
10.
Transplant Proc ; 38(7): 2339-41, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16980084

RESUMO

The predictive factors for cytomegalovirus (CMV) infection in de novo liver transplant patients were determined at 3 months posttransplantation. We included all consecutive patients except those who died or who had lost their graft within 1 month posttransplant. We recorded both donor (D) and recipient (R) data. Immunosuppression utilized tacrolimus, steroids, with or without mycophenolate mofetil, and/or induction therapy with anti-CD25 monoclonal antibodies. CMV prophylaxis was administered only to those at high risk of CMV infection, namely, D+/R- patients. These cases received intravenous ganciclovir at 500 mg/d for the first 2 weeks followed by oral ganciclovir at 500 mg for the following 3 months. The median time to CMV infection was 1 month. The significant predictive factors for CMV infection were D/R CMV status, (P = .002): D+/R+ versus other patients (P = .01), D-/R- versus other patients (P = .002), D+ versus D- (P = .009). In addition infection was associated with the original liver disease (hepatitis C virus infection or alcohol-related cirrhosis; P = .03), R+ vs. R- (P = .03), donor age (<45 or >45 years; P = .01), lymphocyte count at M2 (< or >1300/mm(3); P = .02), hemoglobin levels at 1 and 3 months, and platelet and white blood cell counts at day 7. The independent predictive factors were recipient CMV sero-status (R+ vs R-; odds ratio = 10.2), donor age >45 years (odds ratio = 11.4) and lymphocyte count at M2 <1300/mm(3) (odds ratio = 7.33). This study showed that the major factors associated with CMV infection were recipient CMV status, donor age, and lymphocyte count.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/genética , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/virologia , Sequência de Bases , Citomegalovirus/isolamento & purificação , Primers do DNA , Humanos , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Contagem de Linfócitos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Doadores de Tecidos
12.
Clin Nephrol ; 65(2): 103-12, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16509459

RESUMO

AIMS: To identify the predictive factors for acute renal failure (ARF) in a retrospective study of 100 orthotopic liver transplantations (OLT) performed in 94 patients between 2000 and 2003. METHODS: Acute renal failure (ARF) was defined using the RIFLE criteria, i.e. injury when creatinine doubles or GFR halves, and failure when creatinine trebles or GFR decreases by > 75%. Patients on dialysis pre OLT (n = 3) were excluded from the study. Immunosuppression included steroids, calcineurin inhibitors (CNIs), with (n = 32) or without mycophenolate mofetil. A total of 85% of patients also received induction therapy with antithymocyte globulins (29%) or anti-CD25 monoclonal antibodies (56%). RESULTS: 39 patients (41.5%) and 21 (22.3%) patients developed injury, and failure, respectively. Of these, 10 (10.6%) underwent dialysis. Univariate analysis revealed that acute renal dysfunction with a RIFLE score > or = 3 was significantly associated with a pre-operative serum creatinine level of > 100 micromol/l, pre-operative creatinine clearance of < 75 ml/mn, need for a transfusion (> 10 red packed units), post-operative diuresis of < 100 ml/h, use of vasopressive drugs, times to aspartate (AST) and alanine (ALT) aminotransferase peaks of > 20 and > 24 hours, respectively, relaparotomy, CNIs transient discontinuation, and the use of lower daily dosage of CNIs at post-OLT Days 3, 5, 7 and 15. In multivariate analysis, failure was significantly associated with time to AST peak (> 20 h) (OR 6.35 (1.2 - 33.6), p = 0.029), post-operative diuresis (< 100 ml/h) (OR 9.8 (2.03 47.3), p = 0.004), post-operative use of vasopressive drugs (OR 9.91 (2.02 - 48.7), p = 0.004), and transient CNIs withdrawal (OR 51.08 (7.58-344.1), p < 0.0001). Finally, the occurrence of ARF was significantly associated with an increased number of days on mechanical ventilation, on stay-in intensive care unit (ICU), and on overall hospitalization time. CONCLUSION: ARF is quite common after OLT and significantly increases the post-operative time at the hospital, thereby increasing the OLT cost. Its independent predictive factors are mainly related to perioperative events.


Assuntos
Injúria Renal Aguda/epidemiologia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Condicionamento Pré-Transplante/métodos , Injúria Renal Aguda/terapia , Distribuição de Qui-Quadrado , Creatinina/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Diálise Renal , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
13.
J Viral Hepat ; 12(4): 405-13, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15985012

RESUMO

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.


Assuntos
Hepacivirus/classificação , Hepacivirus/genética , Adulto , Estudos de Coortes , Feminino , França/epidemiologia , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/fisiopatologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Reação em Cadeia da Polimerase , RNA Viral/genética
14.
Transplant Proc ; 36(9): 2757-61, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15621141

RESUMO

BACKGROUND: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). However, in recent years, the long-term results of OLT in this setting are worsening, possibly due to the powerful immunosuppressants in use. The aim of our study was to assess the safety and efficacy of induction therapy using rabbit antithymocyte globulin antibodies (RATG). METHODS: Over an 18-month period from January 2000 to June 2001, 16 patients underwent OLT for HCV-related ESLD and survived more than 1 month posttransplantation. They received induction therapy based on RATG (Thymoglobulins, Sangstat, France) at 1 mg/kg per day for 3 consecutive days, and it was then adjusted to maintain a CD2 count below 50/mm(3). Overall, RATG was given for a median of 5 days for a total dose of 406 +/- 45 mg. Steroids were started pretransplant and tacrolimus on day 1. The primary end-points were patient and graft survivals at 6 months posttransplantation, incidence of rejection, infectious complications (bacterial, viral, and fungal) and recurrence of HCV infection based on biochemical, virological, and histologic criteria. RESULTS: The survival rates were 100% for patients and 93.7% for grafts. The acute rejection rate was 37.5%. The median time to acute rejection was 15.5 days. There was only one serum sickness case. Cytomegalovirus infections occurred in 25% of patients. The rate of de novo diabetes that required insulin therapy was at 50%. The rate of HCV recurrence was 56.25%. In addition, HCV RNA serum concentrations increased significantly posttransplantation (>1 log). In conclusion, RATG induction therapy is safe and efficient in HCV-positive liver recipients.


Assuntos
Soro Antilinfocitário/uso terapêutico , Hepatite C/cirurgia , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Adulto , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Feminino , Humanos , Contagem de Leucócitos , Falência Hepática/cirurgia , Falência Hepática/virologia , Transplante de Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Coelhos , Estudos Retrospectivos , Segurança , Tacrolimo/uso terapêutico , Doadores de Tecidos
15.
J Infect Dis ; 189(8): 1397-400, 2004 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-15073676

RESUMO

Twenty-six patients living in the Midi-Pyrenees region of France who were infected with hepatitis C virus (HCV) genotype 5 were investigated. Most of these patients were of advanced age and had been infected nosocomially or by blood transfusion. Our case-control study, in which we treated patients with interferon- alpha plus ribavirin, indicated that, 24 weeks after the beginning of treatment, the virus response in patients infected with HCV genotype 5 was better than that in patients infected with HCV genotype 1 (100% of patients negative for detectable HCV RNA vs. 36.3%, respectively; P < .01); furthermore, 48 weeks after the end of treatment, the virus response in patients infected with HCV genotype 5 was better than that in patients infected with HCV genotype 1 (63.6% vs. 22.7%, respectively; P < .05) and was similar to that in patients infected with HCV genotype 2 or 3 (66.6%). These results show that HCV genotype 5 might have good intrinsic sensitivity to combination therapy with interferon- alpha plus ribavirin.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Sequência de Bases , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , França/epidemiologia , Genótipo , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Viral/sangue , RNA Viral/química , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
18.
J Vasc Interv Radiol ; 11(9): 1211-6, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11041481

RESUMO

PURPOSE: To assess the efficacy, morbidity, and mortality involved in the creation of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with refractory ascites in Child-Pugh classes B and C. MATERIALS AND METHODS: Forty-eight consecutive patients with refractory ascites were treated with TIPS creation in a tertiary care institution. They were followed for a median of 337 days (range, 3-1376 d). RESULTS: TIPS significantly decreased the portohepatic pressure gradient (20.7 +/- 5.9 mm Hg vs. 6.8 +/- 4.1 mm Hg; P < .0001). Seventy-three percent of patients had complete or partial response. One year after TIPS creation, survival was 73% in Child class B patients and 56% in Child class C patients. Thirteen patients experienced procedural complications (portal vein thrombosis, peritoneal bleeding, acute renal failure, pneumothorax, hemoptysis, spontaneous bacterial peritonitis, and heart failure) and TIPS creation was considered the cause of death in five patients (10.4%). Primary patency was 65% at 3 months and 23% at 1 year, but shunt obstruction was accessible for a second intervention. Ten patients (21%) had de novo encephalopathy after TIPS creation. CONCLUSIONS: This series suggests that TIPS is an effective treatment for refractory ascites; however, it is a challenging procedure and serious complications--usually renal and heart failure--can be seen. A careful selection of patients is mandatory.


Assuntos
Ascite/terapia , Derivação Portossistêmica Transjugular Intra-Hepática , Ascite/etiologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
J Hepatol ; 31(4): 612-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10551383

RESUMO

BACKGROUND/AIMS: High serum levels of the soluble interleukin 2 receptor (sIL-2R) have been reported in patients with chronic hepatitis C. The aims of this study were to determine the evolution of sIL-2R considered as an indicator of activation of T cells in patients with hepatitis C virus (HCV) treated with IFN-alpha and to correlate sIL-2R serum levels with parameters reflecting ongoing liver disease and with outcome of interferon treatment. METHODS: In a case-control study, we studied patients enrolled in a multicenter randomized clinical trial which had demonstrated the benefit of a reinforced regimen of interferon alpha. Each of the 26 sustained virological responders (SVR) was paired for treatment regimen with two non-responders (NR). RESULTS: Prior to treatment, higher levels of sIL-2R were found in the sera of 78 patients compared with healthy controls (3791+/-210 pg/ml versus 956+/-88 pg/ml (p<0.001)). In the 78 patients after 4 weeks of treatment, the levels of sIL-2R were higher than pretreatment levels (4308+/-206 pg/ml (p<0.01)). In the NR, levels of sIL-2R increased significantly after 4 weeks of treatment compared with pretreatment levels (p<0.01), and levels of sIL-2R at week 72 were not significantly different from those at pretreatment. Conversely, in the SVR, levels of sIL-2R at week 4 did not significantly increase compared to pretreatment values, and thereafter gradually decreased. At week 72, levels of sIL-2R were significantly lower than before treatment (p<0.001). The difference between levels of sIL-2R at week 4 and before initiation of treatment (delta s IL-2R) was smaller in the SVR than in the NR (142+/-219 pg/ml versus 704+/-107 pg/ml (p<0.02). The disappearance of HCV RNA from the serum at week 4 showed a sensitivity of 92% (95% confidence interval 86-98) and a specificity of 60% (95% confidence interval 49-71), delta sIL-2R had a sensitivity of 42% (95% confidence interval 31-53) and a specificity of 81% (95% confidence interval 79-90) for the prediction of a sustained virological response 6 months after stopping treatment. The disappearance of HCV RNA from serum at week 4 and delta sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment. CONCLUSIONS: At week 4, delta sIL-2R may be a more specific parameter than the disappearance of HCV RNA for assessing total, and hence more sustained, elimination of HCV infection 6 months after stopping treatment.


Assuntos
Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Receptores de Interleucina-2/sangue , Adulto , Alanina Transaminase/sangue , Feminino , Hepacivirus/genética , Hepatite C Crônica/patologia , Humanos , Fígado/patologia , Masculino , Prognóstico , RNA Viral/sangue , Valores de Referência , Solubilidade , Resultado do Tratamento
20.
Hepatology ; 30(5): 1139-43, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10534333

RESUMO

The optimal management of ruptured gastric varices in patients with cirrhosis has not been codified yet. The present study reports the use of transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory gastric variceal bleeding. Thirty-two consecutive patients were included. All had been unresponsive to vasoactive agents infusion, sclerotherapy, and/or tamponade and were considered poor surgical candidates. They were followed-up until death, transplantation, or at least 1 year (median: 509 days; range 4 to 2,230). Hemostasis was achieved in 18 out of 20 patients actively bleeding at the time of the procedure. In the whole sample of 32 patients, rebleeding rates were 14%, 26%, and 31%, respectively at 1 month, 6 months, and 1 year. De novo encephalopathy was observed in 5 (16%) patients. Seven patients experienced complications and consequently 4 of these patients died. TIPS primary patency rates were 84%, 74%, and 51%, respectively, at 1 month, 6 months, and 1 year. For the same periods of time, survival rates were 75%, 62%, and 59%. These results suggest that TIPS can be used in cirrhotic patients with refractory gastric variceal bleeding and are effective in achieving hemostasis as well as in preventing rebleeding.


Assuntos
Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática , Análise Atuarial , Causas de Morte , Varizes Esofágicas e Gástricas/mortalidade , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Ruptura Espontânea , Análise de Sobrevida
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