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1.
J Hepatol ; 69(4): 776-784, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30104154

RESUMO

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up antiviral treatment through decentralized services. However, access to the conventional tools to assess treatment eligibility (liver biopsy/Fibroscan®/HBV DNA) is limited and not affordable in resource-limited countries. We developed and validated a simple score to easily identify patients in need of HBV treatment in Africa. METHODS: As a reference, we used treatment eligibility determined by the European Association for the Study of the Liver based on alanine aminotransferase (ALT), liver histology and/or Fibroscan and HBV DNA. We derived a score indicating treatment eligibility by a stepwise logistic regression using a cohort of chronic HBV infection in The Gambia (n = 804). We subsequently validated the score in an external cohort of HBV-infected Africans from Senegal, Burkina Faso, and Europe (n = 327). RESULTS: Out of several parameters, two remained in the final model, namely HBV e antigen (HBeAg) and ALT level, constituting a simple score (treatment eligibility in Africa for the hepatitis B virus: TREAT-B). The score demonstrated a high area under the receiver operating characteristic curve (0.85, 95% CI 0.79-0.91) in the validation set. The score of 2 and above (HBeAg-positive and ALT ≥20 U/L or HBeAg-negative and ALT ≥40 U/L) had a sensitivity and specificity for treatment eligibility of 85% and 77%, respectively. The sensitivity and specificity of the World Health Organization criteria based on the aspartate aminotransferase-to-platelet ratio index (APRI) and ALT were 90% and 40%, respectively. CONCLUSIONS: A simple score based on HBeAg and ALT had a high diagnostic accuracy for the selection of patients for HBV treatment. This score could be useful in African settings. LAY SUMMARY: Limited access to the diagnostic tools used to assess treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an obstacle to the scale up of hepatitis B treatment programs in low- and middle-income countries. Using the data from African patients with chronic HBV infection, we developed and validated a new simple diagnostic score for treatment eligibility, which only consists of hepatitis B virus e antigen and alanine aminotransferase level. The diagnostic accuracy of the score for selecting patients for HBV treatment was high and could be useful in African settings.


Assuntos
Alanina Transaminase/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Seleção de Pacientes , Adulto , Feminino , Hepatite B Crônica/diagnóstico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Organização Mundial da Saúde
2.
J Hepatol ; 60(1): 46-53, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23978720

RESUMO

BACKGROUND & AIMS: We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. METHODS: Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. RESULTS: After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). CONCLUSIONS: Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Cacau , Café , Coinfecção/fisiopatologia , Infecções por HIV/fisiopatologia , Hepatite C/fisiopatologia , Adulto , Estudos de Coortes , Coinfecção/enzimologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/enzimologia , Hepatite C/complicações , Hepatite C/enzimologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
3.
J Hepatol ; 61(4): 770-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24905490

RESUMO

BACKGROUND & AIMS: HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment. METHODS: We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance. RESULTS: Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner. CONCLUSIONS: This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance.


Assuntos
Infecções por HIV , Hepacivirus , Hepatite C , Interferon-alfa/administração & dosagem , Interleucinas/genética , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , beta 2-Glicoproteína I , Adulto , Idoso , Antivirais/administração & dosagem , Coinfecção , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/genética , Hepatite C/imunologia , Hepatite C/fisiopatologia , Humanos , Interferons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Carga Viral , Replicação Viral/efeitos dos fármacos , beta 2-Glicoproteína I/sangue , beta 2-Glicoproteína I/genética
4.
Cytokine ; 63(2): 105-12, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23664274

RESUMO

Egypt has the highest prevalence of hepatitis C virus infection worldwide. CXCL10 is a potent chemoattractant that directs effector lymphocytes to sites of inflammation. It has been reported that plasma CXCL10 is processed by dipeptidylpeptidase IV (DPPIV) thus leading to the generation of an antagonist form. Using Luminex-based immunoassays we determined the concentration of different forms of CXCL10 (total, agonist, and antagonist). We also evaluated plasma soluble DPPIV (sDPPIV) concentration and plasma dipeptidylpeptidase (DPP) activity. Using flow cytometry and immunohistochemistry, we analyzed the distribution of lymphocyte subsets. Plasma CXCL10 was elevated in chronic HCV patients, however the agonist form was undetectable. Increased sDPPIV concentration and DPP activity supported the NH2-truncation of CXCL10. Finally, we demonstrated an increased frequency of CXCR3(+) cells in the peripheral blood, and low numbers of CXCR3(+) cells within the lobular regions of the liver. These findings generalize the observation of chemokine antagonism as a mechanism of immune modulation in chronic HCV patients and may help guide the use of new therapeutic immune modulators.


Assuntos
Quimiocina CXCL10/sangue , Dipeptidil Peptidase 4/sangue , Hepatite C Crônica/imunologia , Adolescente , Adulto , Quimiocina CXCL10/antagonistas & inibidores , Dipeptidil Peptidases e Tripeptidil Peptidases/sangue , Egito , Feminino , Hepacivirus/imunologia , Hepatite C Crônica/virologia , Humanos , Inflamação/imunologia , Fígado/citologia , Fígado/imunologia , Fígado/metabolismo , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores CXCR3/metabolismo , Adulto Jovem
6.
AIDS Care ; 23(4): 501-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21271404

RESUMO

Chronic hepatitis B virus (HBV) infection affects up to 14% of people living with HIV and AIDS (PLWHA) and is associated with a higher risk of non-AIDS death. While great advances have been made in the therapeutic management of co-infection with HIV and HBV, nothing is known about perceived health in people living with HIV and HBV. This study aimed at characterizing individuals with poor perceived overall health among 308 HIV-HBV co-infected individuals enrolled between May 2002 and May 2003 in a three-year French cohort. A binary score for perceived overall health (good vs. poor) was calculated from individuals' responses to the COOP-WONCA charts at cohort enrolment and at quarterly visits throughout the follow-up. Mixed models were used to explore factors associated with this score. At enrolment, 190 individuals (62%) reported poor overall health. In the multivariate analysis, low CD4 percentage, co-infection with hepatitis C or D viruses, HIV diagnosis before 1996 and HBeAg positivity were independently associated with poor perceived overall health. Poor perceived health concerns a considerable portion of individuals living with HIV and HBV. Individuals with wild-type HBV and multiple hepatitis infection require better clinical management. Further research is needed for hepatitis D virus infection, for which treatment options are currently very limited.


Assuntos
Sintomas Afetivos , Infecções por HIV/complicações , Nível de Saúde , Hepatite B Crônica/complicações , Hepatite C/complicações , Hepatite D/complicações , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Métodos Epidemiológicos , Feminino , Infecções por HIV/psicologia , Soropositividade para HIV/tratamento farmacológico , Hepatite B Crônica/psicologia , Humanos , Masculino , Fatores de Risco , Autoavaliação (Psicologia) , Fatores de Tempo
7.
Clin Infect Dis ; 50(8): 1184-6, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20210647

RESUMO

We assessed the safety and immunogenicity of hepatitis B vaccination among 40 human immunodeficiency virus-infected patients with isolated positivity for antibodies to hepatitis B core antigen. No baseline factors were found to be predictive of an anamnestic response, which occurred in 32.5% of the patients. The overall response rate among patients without an anamnestic response was 74.0% after 3-6 vaccine doses.


Assuntos
Infecções por HIV/imunologia , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/imunologia , Adulto , Feminino , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade
8.
J Antimicrob Chemother ; 65(11): 2436-44, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20843990

RESUMO

OBJECTIVES: We evaluated a monotherapy maintenance regimen with lopinavir/ritonavir versus continuing current combined antiretroviral treatment (cART) in HIV patients with suppressed plasma HIV-1 RNA. PATIENTS AND METHODS: This was an open-label, non-inferiority, multicentre trial in 23 sites in France. Adults were randomized if they had no history of virological failure while receiving a protease inhibitor, maintained HIV-1 RNA <50 copies/mL for at least 6 months and did not change cART during the last 3 months. The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48 (non-inferiority margin set at -12%) with missing data and treatment modification considered as failure. The trial has been registered in ClinicalTrials.gov under the identifier NCT00140751. RESULTS: At Week 48, 84% (73/87) of patients in the lopinavir/ritonavir monotherapy group met the primary endpoint compared with 88% (87/99) in the cART group [difference, -4.0%, lower limit of 90% two-sided confidence interval (CI) for difference, -12.4%]. In secondary analysis with success defined as plasma HIV-1 RNA <400 copies/mL, 87% (76/87) of patients in the lopinavir/ritonavir monotherapy group were virologically suppressed compared with 88% (87/99) in the cART group (difference, -0.5%, lower limit of 90% two-sided CI for difference, -8.5%). If antiretroviral treatment intensification was taken into account, 91% (79/87) of patients in the lopinavir/ritonavir monotherapy group met the primary endpoint compared with 88% (87/99) in the cART group (difference, +2.9%, lower limit of 90% two-sided CI for difference, -4.5%). Failures of lopinavir/ritonavir monotherapy did not show acquired resistance mutations in the protease gene. CONCLUSIONS: Lopinavir/ritonavir monotherapy did not achieve non-inferiority versus cART for maintaining plasma HIV-1 RNA <50 copies/mL. Nevertheless, the incidence of virological failure was low (mostly with HIV-1 RNA <400 copies/mL) and easily managed by treatment intensification.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Pirimidinonas/administração & dosagem , Ritonavir/administração & dosagem , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , França , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Resultado do Tratamento , Carga Viral
9.
BMC Infect Dis ; 10: 303, 2010 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-20969743

RESUMO

BACKGROUND: In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date. METHODS: Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrollment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrollment and yearly thereafter. RESULTS: A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrollment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/µl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status. CONCLUSION: The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Carcinoma Hepatocelular/epidemiologia , Progressão da Doença , Feminino , França/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , HIV-1/isolamento & purificação , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Humanos , Neoplasias Hepáticas/epidemiologia , Estudos Longitudinais , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , RNA Viral/sangue , Fatores de Risco , Inquéritos e Questionários , Carga Viral
10.
J Hepatol ; 50(6): 1074-83, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19398234

RESUMO

BACKGROUND/AIMS: The aim of this study was to compare the performance of 11 biochemical scores to estimate liver fibrosis in HIV/HBV co-infection. METHODS: Performance was evaluated using the Receiver Operating Characteristics (ROC) curve method. The Kappa index was used to study overall agreement with liver biopsy results. Interpretative algorithms were established by optimizing sensitivity and specificity and the percentage of correctly classified patients. RESULTS: One hundred and eight patients (F0-F1, n = 47; F2, n = 28; F3, n = 17; F4, n = 16) were considered for the evaluation of serum biomarker performance. The AUROCs of the Fibrotest, Hepascore, Fibrometer, and Zeng's scores ranged from 0.74 to 0.77 for significant fibrosis (> or = F2), from 0.79 to 0.84 for advanced fibrosis (> or = F3) and from 0.87 to 0.92 for cirrhosis (F4). Thresholds defined for each stage of fibrosis were close to those previously published for the Fibrotest and Hepascore. Strict concordance with biopsies correctly classified 50% of the patients. CONCLUSIONS: Fibrotest, Fibrometer, Hepascore, and Zeng's score were the most accurate non-invasive biochemical scores for liver fibrosis assessment in HIV/HBV co-infection. Global performance of biomarkers was not significantly improved by a decision tree combining the results of two biochemical scores.


Assuntos
Biomarcadores/sangue , Infecções por HIV/sangue , Infecções por HIV/complicações , Hepatite B/sangue , Hepatite B/complicações , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Adulto , Algoritmos , Biópsia , Análise Química do Sangue/métodos , Análise Química do Sangue/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
11.
AIDS Rev ; 10(2): 85-92, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18615119

RESUMO

Syphilis has been a public health problem for centuries. Syphilis and HIV form a dangerous combination: syphilis significantly increases the risk of contracting HIV infection, and HIV can alter the natural course of syphilis. Despite a better understanding of the interaction between these two diseases, many controversies persist. The incidence of syphilis has increased among HIV-infected patients both in Europe and in the USA, and especially in the homosexual/bisexual transmission group. We discuss the interaction between HIV/AIDS and syphilis in a review of the most recent literature, focusing particularly on the diagnosis, treatment, and follow-up of HIV-infected patients with syphilis. Early diagnosis of syphilis in HIV-infected patients requires awareness among both patients and clinicians. Early treatment of syphilis is crucial as it reduces the risk of transmission.


Assuntos
Infecções por HIV/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Bissexualidade , Europa (Continente)/epidemiologia , Homossexualidade , Humanos , Sífilis/epidemiologia , Estados Unidos/epidemiologia
13.
Antivir Ther ; 13(5): 705-13, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18771054

RESUMO

BACKGROUND: Characteristics and factors influencing viral decay under tenofovir (TDF) and adefovir (ADV) need to be determined in HIV-HBV-coinfected patients. METHODS: This open-label study compared the HBV dynamics in 85 HIV-HBV-coinfected patients initiating an antiretroviral regimen, either including TDF or associated with ADV. The first 6-month change in viral load was analysed using mixed linear models. The adjusted hazards ratio, comparing the rates of undetectable HBV DNA between treatments, was calculated using a Cox proportional hazard model. RESULTS: The HBV DNA decay, adjusted for baseline HBV viral load was more pronounced in patients treated with TDF than with ADV at 12 months (66% versus 53%, P=0.0001). Patients in the TDF group presented a steeper slope of decline at 1.1 (95% confidence interval [CI] 0.9-1.3), compared with 0.8 (95% CI 0.6-1.0) in the ADV group (P=0.036). The mean time to HBV DNA undetectability was 19.3 months (95% CI 16.7-22.0) with TDF and 25.9 months (95% CI 21.1-30.7) with ADV. When adjusted for hepatitis B virus e antigen, HBV DNA and alanine aminotransferase levels at baseline, the influence of treatment on time to HBV DNA undetectability remained in favour of TDF versus ADV (hazard ratio=2.79, 95% CI 1.05-7.40, P=0.039) CONCLUSIONS: TDF influenced more strongly the early-phase HBV DNA kinetics than ADV. This is associated with a sustained antiviral activity in the TDF group, in which patients reached the threshold of HBV undetectability at a faster rate and in a larger proportion than those taking ADV.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Infecções por HIV , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B , Organofosfonatos/uso terapêutico , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Antivirais/farmacologia , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/farmacologia , Modelos de Riscos Proporcionais , Tenofovir , Resultado do Tratamento , Carga Viral
14.
Antivir Ther ; 12(7): 1115-26, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18018770

RESUMO

BACKGROUND: Little is known about the prognostic factors of acute liver enzyme variations in HIV-hepatitis B virus (HBV)-coinfected patients. OBJECTIVES: To identify prognostic factors of acute liver enzyme abnormalities in HIV-HBV-coinfected patients with a focus on the putative role of antiretroviral drugs. DESIGN: Data from a 3-year, prospective, multicentre cohort study involving HIV-HBV patients were used. METHODS: A Markov model was used to identify prognostic factors of acute episodes of cytolysis and cholestasis in 300 HIV-HBV-coinfected patients. The effect of antiretroviral therapy was analysed according to the classes of drugs, duration of treatment and treatment modifications. RESULTS: The incidence rates of acute episodes of cytolysis and cholestasis were 13.4 per 100 patient-years (95% confidence interval [CI] 9.5-17.3) and 7.1 per 100 patient-years (95% CI 4.2-10.0), respectively (median follow up 34.1 months). Independent risk factors for cytolysis were a high level of HBV or HIV replication, as well as a low of CD4+ T-cell count. No antiretroviral drug was associated with cytolysis, whereas protease inhibitors seemed to be independently associated with cholestasis, along with treatment modifications and the duration of HIV infection. CONCLUSION: Acute and reversible episodes of cytolysis or cholestasis were common and associated with virus- and host-related determinants. The choice of the optimal antiretroviral combination in HIV-HBV-coinfected patients must take into account the necessity of exerting an efficient control of HIV and HBV replication (associated with transient cytolysis) and the risk of inducing cholestasis (associated with the use of protease inhibitors and treatment modifications).


Assuntos
Terapia Antirretroviral de Alta Atividade , Colestase/etiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite B/complicações , Hepatopatias/etiologia , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Feminino , HIV/isolamento & purificação , Infecções por HIV/virologia , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carga Viral
15.
AIDS ; 20(8): 1157-61, 2006 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-16691067

RESUMO

BACKGROUND: Treatment of acute hepatitis C (HCV) in HIV-infected patients has been poorly addressed. OBJECTIVE: To evaluate the efficacy and tolerability of a 24 week course of pegylated interferon alfa 2a (PegIFNalpha2a) and ribavirin for the treatment of acute HCV infection in HIV-infected patients. METHODS: This was a prospective pilot study of 25 consecutive HIV-infected men with acute HCV infection defined by documented HCV seroconversion to anti-HCV positive antibody and positive qualitative HCV RNA measurement. Patients with detectable HCV RNA (> 50 IU/ml) 12 weeks after diagnosis were offered treatment with PegIFNalpha2a (180 microg/week) and ribavirin (800 mg/day) for 24 weeks. Sustained virological response was defined by a negative qualitative HCV RNA measurement 24 weeks after the end of treatment. RESULTS: At baseline, 23 patients were taking HAART, 23 patients had HIV RNA < 200 copies/ml and a median CD4 count of 345 cells/microl. Only one patient, with genotype 3 HCV, had a spontaneous clearance of HCV RNA. Of the remaining 24 patients, four refused anti-HCV therapy, ribavirin was contraindicated in one and 19 initiated anti-HCV therapy. Median time between acute HCV diagnosis and initiation of study treatment was 14 weeks. Of the 14 patients who have achieved the post-treatment follow-up at 24 weeks, 10 had a sustained virological response (71%). Study treatment was well tolerated, with no change in CD4 cell count. CONCLUSION: Early treatment of acute HCV infection with PegIFNalpha2a and ribavirin for 24 weeks yields a high sustained virological response rate in HIV-infected patients.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Doença Aguda , Adulto , Terapia Antirretroviral de Alta Atividade , Antivirais/efeitos adversos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/isolamento & purificação , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Hepatite C/imunologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversos , Resultado do Tratamento , Carga Viral
16.
Trans R Soc Trop Med Hyg ; 99(1): 82-6, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15550267

RESUMO

Malaria is the most frequent cause of fever among travellers returning from tropical countries. Each year about 7000 cases are notified in France, of which 90% are due to Plasmodium falciparum. We describe the case of a Caucasian female patient with no previous exposure to malaria in whom splenic infarction occurred during effective antimalarial treatment for initially uncomplicated acute malaria. Management was restricted to close clinical monitoring and analgesia (subcutaneous morphine). Imaging abnormalities resolved within a few months. We found seven other such cases in the literature. All seven patients were younger and splenic infarction occurred later than in the case we describe. Clinical outcome was favourable in all the cases. It is noteworthy that this rare complication can occur despite appropriate antimalarial prophylaxis and treatment. There are no known predictive signs. Clinicians must be aware that left hypochondrial pain occurring during treatment for acute malaria may be due to splenic infarction.


Assuntos
Malária Falciparum/complicações , Infarto do Baço/etiologia , Doença Aguda , Administração Oral , Adulto , Antimaláricos/administração & dosagem , Feminino , Humanos , Malária Falciparum/diagnóstico por imagem , Malária Falciparum/tratamento farmacológico , Quinina/administração & dosagem , Infarto do Baço/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
17.
Am J Trop Med Hyg ; 71(2): 202-5, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15306711

RESUMO

Since the few indirect markers available for assessing the development and the stage of intestinal schistosomiasis morbidity are weakly specific, endoscopy is still the only method able to detect severe forms of pathology. Therefore, we evaluated the isotype antibody response to the current schistosome antigen preparation (soluble egg antigens [SEA]) in 142 Senegalese patients infected with Schistosoma mansoni. They were stratified into three different stages of pathology according to ultrasonographic, endoscopic, and clinical parameters (stage 1 = no detectable pathology; stage 2 = moderate morbidity; stage 3 = severe forms of pathology). Only median specific IgG4, IgE, and IgA responses changed according to the stage of pathology. The IgA level was significantly higher in stages 2 and 3 compared with stage 1, and the IgE level was higher in stage 3 compared with stage 1. A high specific IgG4 level was observed only in stage 3 and was significantly different compared with stage 2. We show an association between the variability of the specific response to SEA and the degree of morbidity, and demonstrate that IgA and IgG4 responses could be combined markers to easily discriminate the different stages of pathology due to infection with S. mansoni.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Isotipos de Imunoglobulinas/sangue , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Especificidade de Anticorpos , Antígenos de Helmintos/imunologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquistossomose mansoni/diagnóstico , Índice de Gravidade de Doença
18.
Eur J Gastroenterol Hepatol ; 14(2): 153-8, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11981339

RESUMO

OBJECTIVES: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin has been studied in several reports, two prospective pilot studies and a double-blind, short-term, controlled haemodynamic study. Promising results have been shown with this drug. The purpose of this multicentre retrospective study was to evaluate the effects of terlipressin on renal function and survival of patients with HRS. PATIENTS AND METHODS: Eighteen patients recruited in three liver units with type 1 HRS in 16 cases and type 2 HRS in two cases were given 4 mg/day terlipressin (range 1.5-12) for 7 days (range 2-16). Electrolytes, renal function, mean urinary output, natriuresis, liver function tests, and tolerance of the treatment were monitored regularly. RESULTS: A total of 13/18 (72%) patients responded with a mean decline in serum creatinine ranging from 31 to 75% from day 0 to day 5. Eight of these 13 patients had a normal serum creatinine level at day 5. Liver function tests remained unaffected by terlipressin administration. Three local necrosis complications were noted in patients receiving terlipressin continuously via an infusion pump. Two responder patients survived: one of these underwent orthotopic liver transplantation with a follow-up of 24 months; the other is alive with a follow-up of more than 36 months. Patients who responded to terlipressin had lower baseline serum bilirubin and significantly higher serum sodium concentrations than patients who did not respond. CONCLUSION: In this pilot study, improvement in renal function was noted in 72% of cases after administration of terlipressin, and was associated with long-term survival in two patients. Parameters associated with response to terlipressin and increased survival should be defined better in a large cohort of cirrhotic patients with HRS.


Assuntos
Síndrome Hepatorrenal/tratamento farmacológico , Lipressina/uso terapêutico , Vasoconstritores/uso terapêutico , Idoso , Creatinina/sangue , Feminino , Hemodinâmica , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/mortalidade , Síndrome Hepatorrenal/fisiopatologia , Humanos , Cirrose Hepática/complicações , Testes de Função Hepática , Lipressina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Terlipressina
19.
PLoS One ; 7(11): e50289, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23226258

RESUMO

BACKGROUND AND AIMS: Hepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV-HCV co-infected patients. METHODS: We used a phenotypic assay to assess HIV tropism in 172 HCV-HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness. RESULTS: Initially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: <200/mm(3) (OR: 3.94, 95%CI: 1.39-11.14). The median HCV RNA concentrations in patients infected with R5 viruses, those with dual-mixed viruses and those with X4 viruses, were all similar. The prevalence of CXCR4-using viruses in patients with mild fibrosis (≤F2) (31%) and those with severe fibrosis (F3-F4) (28%, p = 0.6) was similar. Longitudinal analyses showed that the presence of CXCR4-using viruses did not increase the likelihood of fibrosis progression, evaluated by measuring liver stiffness. CONCLUSIONS: The presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis.


Assuntos
Infecções por HIV/patologia , HIV-1/metabolismo , Hepacivirus/metabolismo , Hepatite C/patologia , Cirrose Hepática/patologia , RNA Viral/biossíntese , Tropismo Viral/fisiologia , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Antivirais/farmacologia , Antivirais/uso terapêutico , Coinfecção , Progressão da Doença , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Células Estreladas do Fígado/virologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo
20.
Antivir Ther ; 17(7): 1335-43, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23052829

RESUMO

BACKGROUND: The aim of this study was to describe changes in repeated liver stiffness (LS) measurements and to assess the determinants of increase in LS in HIV-HCV-coinfected patients. METHODS: HIV-HCV-coinfected adults enrolled in the ANRS CO 13 HEPAVIH cohort, for whom two results of LS, evaluated over ≥24 months, were available. Patients with unreliable LS results were not included. LS was measured at baseline and every year thereafter. Determinants of LS increase were assessed using linear (primary outcome: last LS minus first LS value) and logistic (secondary outcome: ≥30% increase in the initial LS value) regression analyses. RESULTS: A total of 313 patients (mean age 45 years, 67.4% male) were included. Overall, 93.9% were receiving antiretroviral treatment (ART). The mean baseline CD4(+) T-cell count was 471 cells/mm(3) and 72.2% of patients had undetectable plasma HIV RNA. The mean interval between the first and last LS measurements was 33.5 months. No significant difference was found between baseline and follow-up mean LS values (P=0.39). However, a decrease of ≥30% in LS was observed in 48 (15.3%) patients and an increase of ≥30% in 64 (20.5%) patients. In multivariate linear and logistic analyses, excessive alcohol intake (ß coefficient 6.8; P=0.0006) and high HCV viral load (OR 1.7, 95% CI 1.1, 2.5; P=0.01) were independently associated with an increase in LS, whereas time on ART>114.5 months (OR 0.5, 95% CI 0.3, 0.9; P=0.03) and achievement of sustained virological response (OR 0.1, 95% CI 0.01, 0.9; P=0.04) were independently associated with no increase in LS. CONCLUSIONS: Our findings show that long-term ART and achieving sustained virological response in HIV-HCV-coinfected patients are both significantly associated with lack of increase in LS over a 33-month period.


Assuntos
Coinfecção/virologia , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/patologia , Adulto , Alanina Transaminase , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Coinfecção/patologia , Feminino , Seguimentos , HIV/patogenicidade , Infecções por HIV/virologia , Hepacivirus/patogenicidade , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Viral
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