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1.
Gastroenterology ; 156(4): 997-1009.e5, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30768988

RESUMO

BACKGROUND & AIMS: Management of patients with cirrhosis includes endoscopic screening and surveillance to detect esophageal varices (EV) and prevent bleeding. However, the Baveno VI guidelines recommend avoiding endoscopies for patients with liver stiffness measurements below 20 kPa and platelet counts above 150,000 (favorable Baveno VI status) and endoscopic assessment of patients with higher levels of liver stiffness and platelet counts (unfavorable Baveno VI status). We aimed to validate the Baveno VI guidelines, evaluating outcomes of patients in the ANRS-CO12 CirVir cohort with compensated cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, with or without a sustained response to antiviral therapy. METHODS: We performed an ancillary study using data from 891 patients in the ANRS CO12 CirVir cohort, treated at 35 centers in France, with HCV or HBV infection and biopsy-proven cirrhosis, Child-Pugh A scores, no previous complications, and no hepatocellular carcinoma who underwent an endoscopic procedure and had interpretable liver stiffness measurements and platelet counts. Progression of portal hypertension (PHT) was defined as the onset of varices needing treatment (VNT) or PHT-related bleeding. An sustained response to antiviral therapy was defined as undetectable level of HCV RNA by polymerase chain reaction assay (<50 IU/mL) 12 weeks after the end of treatment (SVR) or an undetectable level of HBV DNA. The primary aims were to validate the Baveno VI guidelines for screening and surveillance of EV in patients with compensated cirrhosis and to study the effects of an SVR on the progression of PHT. RESULTS: A total of 200 patients achieved an SVR (22.4%) (94 patients with HCV infection, 98 patients with HBV infection, and 8 patients with both); 80 of these patients had favorable Baveno VI status and none had VNT. Progression of PHT was studied in 548 patients; during a follow-up period of 61.2 months (interquartile range, 39.5-80.6 months), 105 of these patients (19.1%) had progression of PHT. Lack of an SVR and grade 1 EV were independently associated with progression of PHT. At the time of PHT progression, all patients had unfavorable Baveno VI status. Achieving favorable Baveno VI status after an SVR was associated with the absence of PHT progression. Favorable Baveno VI status and SVR were independently associated with survival. CONCLUSIONS: In an analysis of data from a large cohort of patients with HBV- or HCV-associated cirrhosis in France, we validated the Baveno VI guidelines on screening and surveillance of PHT, even for patients who achieved a sustained response to antiviral therapy.


Assuntos
Varizes Esofágicas e Gástricas/diagnóstico por imagem , Cirrose Hepática/fisiopatologia , Programas de Rastreamento/normas , Vigilância da População , Guias de Prática Clínica como Assunto , Antivirais/uso terapêutico , Progressão da Doença , Técnicas de Imagem por Elasticidade , Endoscopia Gastrointestinal , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Taxa de Sobrevida , Resposta Viral Sustentada
2.
Gastroenterology ; 152(1): 142-156.e2, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27641509

RESUMO

BACKGROUND & AIMS: We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis. METHODS: We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR. RESULTS: After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population. CONCLUSIONS: We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite C/tratamento farmacológico , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/epidemiologia , Resposta Viral Sustentada , Idoso , Aspartato Aminotransferases/sangue , Infecções Bacterianas/epidemiologia , Índice de Massa Corporal , Carcinoma Hepatocelular/mortalidade , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Seguimentos , França/epidemiologia , Hepatite C/complicações , Hepatite C/mortalidade , Humanos , Incidência , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Tempo de Protrombina , gama-Glutamiltransferase/sangue
3.
Am Heart J ; 198: 4-17, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29653647

RESUMO

BACKGROUND: The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis. METHODS: Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015. RESULTS: Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P<.001). CONCLUSIONS: In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Distribuição por Idade , Idoso , Antivirais/uso terapêutico , Biópsia por Agulha , Doenças Cardiovasculares/terapia , Estudos de Coortes , Feminino , França , Hepatite C Crônica/fisiopatologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Taxa de Sobrevida
4.
Gut ; 66(2): 330-341, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26511797

RESUMO

OBJECTIVE: To assess incidence and prognostic significance of bacterial infections (BIs) occurring in compensated viral cirrhosis. DESIGN: This prospective study involved 35 French centres. Inclusion criteria were biopsy-proven HCV or HBV cirrhosis, Child-Pugh A and no previous hepatic complications. Cumulative incidence (CumI) of events was estimated in a competing risks framework. RESULTS: 1672 patients were enrolled (HCV 1323, HBV 318, HCV-HBV 31). During a median follow-up of 43 months, 234 BIs occurred in 171 patients (5 year CumI: 12.9%), among whom 14.6% had septic shock. Main localisations included the urinary tract (27.4%), lung (25.2%) and peritoneum (10.7%) (other, 86 (36.7%)). Most BIs occurred as a first event prior to liver decompensation (n=140, 81.8%) and were community-acquired (CA, 84.2%). The risk of BI was higher in patients with HCV than in patients with HBV (5 year CumI: 15.2% vs 5.5%, p=0.0008). Digestive localisation, concomitant interferon-based treatment, isolation of resistant bacteria and non-CA BIs were associated with lowest probability of resolution. The occurrence of a first BI impaired survival in patients infected with HCV (5 year survival: 60.2% vs 90.4%, p<0.001) and patients infected with HBV (5 year survival: 69.2% vs 97.6%, p<0.001). BIs represented the third cause of death (14.1%) after liver failure and liver cancer. BI risk factors comprised older age, lower albumin, proton pump inhibitor intake and absence of virological eradication/control. CONCLUSION: BI mostly occurs as a first complication and represents a turning point in the course of compensated viral cirrhosis. Its occurrence impacts long-term prognosis and may define a subgroup of patients in whom adaptation of management is warranted.


Assuntos
Infecções Bacterianas/mortalidade , Coinfecção/mortalidade , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/mortalidade , Adulto , Causas de Morte , Feminino , França/epidemiologia , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Incidência , Cirrose Hepática/virologia , Falência Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Peritonite/microbiologia , Peritonite/mortalidade , Pneumonia/mortalidade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Infecções Urinárias/mortalidade
5.
Hepatology ; 64(4): 1136-47, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27348075

RESUMO

UNLABELLED: The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)-compensated cirrhosis. Among 1,323 patients with HCV cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow-up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (<100 Giga/mm(3) : HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; [100; 150] Giga/mm(3) : HR, 1.87; 95% CI, 1.10; 3.18; P = 0.021); gamma-glutamyl transpeptidase above the upper limit of normal (HR, 1.96; 95% CI, 1.11; 3.47; P = 0.021); and absence of a sustained virological response during follow-up (HR, 3.02; 95% CI, 1.67; 5.48; P < 0.001). An 11-point risk score was derived from the training cohort and validated in the validation set. Based on this score, the population was stratified into three groups, in which HCC development gradually increased, from 0% to 30.1% at 5 years for patients with the lowest (≤3) and highest (≥8) scores (P < 0.001). Using this score, a nomogram was built enabling individualized prediction of HCC occurrence at 1, 3, and 5 years. CONCLUSION: This HCC score can accurately predict HCC at an individual level in French patients with HCV cirrhosis. (Hepatology 2016;64:1136-1147).


Assuntos
Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Nomogramas , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Hepatology ; 62(3): 737-50, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25678021

RESUMO

UNLABELLED: Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20). CONCLUSION: After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control.


Assuntos
Carcinoma Hepatocelular/virologia , Causas de Morte , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Adulto , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , França , Hepatite B/complicações , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/patologia , Humanos , Cirrose Hepática/complicações , Falência Hepática/mortalidade , Falência Hepática/patologia , Falência Hepática/virologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida
7.
Scand J Gastroenterol ; 50(4): 470-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25396710

RESUMO

OBJECTIVE: Sofosbuvir and simeprevir in combination with standard therapy are now available for the treatment of patients chronically infected with hepatitis C virus (HCV) genotype 1. With boceprevir and telaprevir, four treatment options are, therefore, now available to clinicians. Phase 3 studies conducted with simeprevir and sofosbuvir compared sustained virological response (SVR) data with those obtained with standard combination therapy and did not include a control arm. It is important to quantify the contribution of these molecules compared to the first direct antiviral agents available. MATERIAL AND METHODS: For HCV genotype 1 patients, we performed a literature review and compared all SVR data from phase 3 randomized placebo-controlled trials conducted with these four molecules according to virological characteristics (genotype, viral load) and patient characteristics (IL28B polymorphism, stage of fibrosis). RESULTS: Simeprevir and sofosbuvir provide a net gain in terms of SVR compared to boceprevir and telaprevir except in the case of telaprevir for treatment-naïve HCV genotype 1b patients. Sofosbuvir achieves higher SVR rates than simeprevir except for treatment-naïve IL28B CC patients and naïve HCV genotype 1b patient. Further, simeprevir moderately improve SVR rates compared to telaprevir in treatment-naïve patients with F3-F4 fibrosis and with HCV genotype 1a infection. CONCLUSION: Sofosbuvir and simeprevir greatly improve the virological response rate compared to first-generation protease inhibitors. All of these data may help in guiding the physician's treatment decisions, based on financial constraints and patient characteristics. These data can be easily updated with future treatment and demonstrate the contribution of new treatment regimens to achieve optimal SVR rates.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Ensaios Clínicos Fase III como Assunto , Genótipo , Hepatite C Crônica/genética , Humanos , Interferons , Interleucinas/genética , Oligopeptídeos/uso terapêutico , Prolina/análogos & derivados , Prolina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Carga Viral
8.
Antimicrob Agents Chemother ; 56(2): 903-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22123700

RESUMO

The current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined therapy. The interferon concentration was measured in serum by a bioassay. The expression of 93 interferon-regulated genes in peripheral blood mononuclear cells was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) before and after 1 month of treatment. The interferon concentration in the serum was significantly lower in nonresponders than in sustained virological responders. Moreover, a significant correlation was identified between interferon concentration and interferon exposition as well as body weight. The analysis of interferon-inducible genes in peripheral blood mononuclear cells among the genes tested did not permit the prediction of treatment outcome. In conclusion, the better option seems to be to treat patients with weight-adjusted PEG-IFN doses, particularly for patients with high weight who are treated with PEG-IFN-α2a. Although the peripheral blood mononuclear cell samples are the easiest to obtain, the measurement of interferon-inducible genes seems not be the best strategy to predict treatment outcome.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/sangue , Leucócitos Mononucleares/metabolismo , Ribavirina/uso terapêutico , Adulto , Antivirais/administração & dosagem , Antivirais/sangue , Antivirais/farmacologia , Peso Corporal , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares/química , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Ribavirina/administração & dosagem , Resultado do Tratamento , Carga Viral
9.
Alcohol Clin Exp Res ; 34(7): 1146-53, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20477777

RESUMO

BACKGROUND: Large esophageal varices (LOV) were diagnosed by endoscopy in patients with cirrhosis. Noninvasive method would be valuable. AIMS: To evaluate the diagnostic performance of Fibroscan for LOV prediction and to investigate the prognostic value of liver stiffness (LS) in cirrhosis. PATIENTS AND METHODS: One hundred and eighty-three patients with cirrhosis (103 alcohol, 58 viral, and 22 others) underwent an endoscopy and a Fibroscan. Of those patients, 41 (22.4%) had LOV. RESULTS: Median LS was 33.66 kPa (range: 12-75), higher in patients with LOV than those without (51.24 +/- 1.61 vs. 29.81 +/- 1.82 kPa, p < 0.0001), and in alcoholic than nonalcoholic (40.39 +/- 1.75 vs. 25.73 +/- 1.82, p < 0.0001). In whole population, a LS > or =48 kPa predicted LOV with sensitivity, specificity, positive, negative predictive values (PPV, NPV) of 73.2, 73.2, 44.1, and 90.4%, respectively, and an area under ROC curve (AUROC) of 0.75 (CI 95%: 0.69-0.82). For alcoholic cirrhosis, LS was > or =47.2 kPa with sensitivity, specificity, PPV, NPV of 84.6, 63.6, 44, and 92.5%, respectively, AUROC 0.77 (0.68-0.85). For viral cirrhosis, a LS > or =19.8 kPa generated diagnostic values of 88.9, 55.1, 26.7, and 96.4% and 0.73 (0.60-0.84). Sixteen (8.75%) patients died at 1 year. In multivariate analysis, LS was not predictive of mortality. CONCLUSIONS: Etiology of cirrhosis has strong impact on LS cutoff for diagnosis of LOV. Studies should be performed with homogenous cirrhosis etiology.


Assuntos
Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/diagnóstico , Adulto , Idoso , Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Esofagoscopia/métodos , Feminino , Seguimentos , Humanos , Cirrose Hepática Alcoólica/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
10.
Eur J Gastroenterol Hepatol ; 20(9): 829-36, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18794595

RESUMO

OBJECTIVES: Although there may exist a nosocomial risk of hepatitis C virus (HCV) infection in patients with type 1 or type 2 diabetes, this risk has not been fully investigated thus far and its magnitude is unknown. The aim of this multicenter cross-sectional study was to evaluate the prevalence of, and risk factors for, hepatitis C infection in consecutive hospitalized patients with diabetes and to assess the nosocomial risk and magnitude of HCV infection in these patients. PATIENTS AND METHODS: Consecutive hospitalized patients with diabetes seen in 11 French hepatogastroenterology and diabetology departments were studied. The prevalence of anti-HCV antibodies was compared with that observed in healthy blood donors and individuals seen during routine medical checkup. Diabetic patients with anti-HCV antibodies were compared with patients without anti-HCV antibodies for assessment of risk factors. RESULTS: In total 1561 patients were studied. Independent risk factors for HCV infection were assessed through multivariate analysis. Thirty-three patients (2.11%) had anti-HCV antibodies and 21 (63.70%) had HCV identified risk factors. The prevalence of HCV infection was higher in patients with diabetes than in blood donors (0.08%) or healthy controls (0.20%) (P<0.001). Multivariate analysis identified four independent risk factors for HCV infection: blood transfusion before 1991 [odds ratio (OR)=2.88, P=0.033], intravenous drug use (OR=21.37, P=0.012), treatment in a hepatogastroenterology center (OR=4.17, P=0.002) and a high number (>2) of previous admissions since the onset of diabetes (OR=2.52, P=0.039). CONCLUSION: A nosocomial source of HCV infection in hospitalized diabetic patients is suggested by the increased risk of HCV infection associated with the number of hospitalizations. This may account for at least 36% of cases of HCV infection.


Assuntos
Diabetes Mellitus/epidemiologia , Hepatite B/epidemiologia , Adulto , Idoso , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Métodos Epidemiológicos , Feminino , França/epidemiologia , Hepatite B/transmissão , Anticorpos Anti-Hepatite C/sangue , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Reação Transfusional
11.
Clin Gastroenterol Hepatol ; 5(4): 502-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17261383

RESUMO

BACKGROUND & AIMS: The impact of interferon (IFN) treatment on the occurrence of complications related to hepatitis C virus (HCV)-related cirrhosis is debated because the majority of studies are retrospective. We designed a randomized controlled trial comparing the efficacy of prolonged IFN alfa-2a treatment vs nontreatment on complication-free survival in patients with compensated HCV cirrhosis. METHODS: A total of 102 patients (mean age, 60.5 +/- 9.5 y; male/female ratio, .82) with biopsy examination-proven HCV cirrhosis, Child-Pugh score A, who were hepatocellular carcinoma (HCC) free, and had at least 1 risk factor of complications were randomized to receive IFN or no therapy for 24 months. RESULTS: During the follow-up evaluation, the complication rate was 24.5%: HCC occurred in 12 and decompensation unrelated to HCC occurred in 13 patients. The number of HCC patients was similar in both groups. The probability of complication-free survival was not significantly different between treated and untreated patients (98% and 72.3% vs 90% and 70.7% at 12 and 24 mo, respectively, P = .59). The median time until complication occurrence was 17.1 months in the treated group vs 13.6 months in the untreated group (P = .2). CONCLUSIONS: This randomized controlled trial showed that a 2-year course of IFN has little or no impact on complication-free survival in patients with high-risk compensated HCV cirrhosis.


Assuntos
Hepatite C Crônica/mortalidade , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Idoso , Antivirais/uso terapêutico , Intervalos de Confiança , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Razão de Chances , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Proteínas Recombinantes , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
Virol J ; 4: 35, 2007 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-17397531

RESUMO

BACKGROUND/AIM: The role of humoral immunity in hepatitis C virus (HCV) infection is poorly understood. Nevertheless, there is increasing interest in characterizing the neutralizing antibodies in the serum of HCV-infected patients. Focus reduction assays have been widely used to evaluate neutralizing antibody responses against a range of non-cytopathic viruses. Based on the recent development of a HCV cell culture system using the genotype 2 JFH-1-strain, we developed a focus reduction assay for HCV-neutralizing antibodies. METHODS: The focus reduction assay was based on a standard microneutralization assay in which immunostained foci on tissue culture plates are counted. The neutralizing anti-HCV antibodies titers of purified serum immunoglobulin samples from seventy-seven individuals were determined using a 50% focus reduction neutralization assay. Each titer was determined as the log value of the reciprocal antibody dilution that reduced the number of viral foci by 50%. IgG antibodies were first purified from each serum in order to avoid the facilitating effect of HDL on HCV entry. RESULTS: The assay's cut-off using an ELISA and RNA HCV-negative samples was found to be 1.25 log, corresponding to a dilution of 1:18. The assay was compared with a commercial HCV ELISA and exhibited specificity and sensitivity values of 100% and 96.5%, respectively, and good reproducibility (with intra-assay and inter-assay coefficients of variation of 6.7% and 12.6%, respectively). The assay did not show any cross-reactivity with anti-HIV, anti-HBs or heterophile antibody-positive samples. The neutralizing antibodies titers were 2.13 log (1:134) for homologous samples from HCV genotype 2 infected patients harboring the same genotype as JFH-1 and 1.93 log (1:85) for heterologous samples from patients infected by genotypes other than type 2. These results confirm the presence of broadly cross-neutralizing antibodies already reported using the HCV pseudoparticles system. CONCLUSION: This study presents a simple, specific and reproducible cell culture-based assay for determination of HCV-neutralizing antibodies in human sera. The assay should be an important tool for gauging the relationship between the neutralizing antibodies response and viral load kinetics in acutely or chronically infected patients and for investigating the possible eradication or prevention of HCV infection by neutralizing antibodies.


Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Testes de Neutralização/métodos , Análise de Variância , Linhagem Celular , Reações Cruzadas , Genótipo , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Eur J Intern Med ; 18(7): 510-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17967331

RESUMO

Pegylated interferon plus ribavirin is the standard treatment for chronic hepatitis C (CHC). It yields sustained virological response (SVR) rates of 42-52% for genotype 1, 66-72% for genotype 4, and 76-80% for genotypes 2 and 3. Hence, the patient's genotype appears to be a determining predictive factor for the SVR. We have reviewed the literature in order to determine whether a genotype-specific treatment duration should be envisaged. The largest study to date of patients infected with HCV genotype 2 or 3 confirmed the value of the standard treatment duration of 24 weeks. Shorter treatments exposed the patients to a greater risk of relapse. For genotype 1, it was possible to offer a shorter, 24-week course of treatment to the 35% of patients with an initial viral load below 600,000 IU/mL and an early virological response (EVR) at week 4 (negative PCR), resulting in an SVR of 89%. For the remaining two-thirds of genotype 1 patients with a high viral load, the treatment duration should remain at 48 weeks. A subgroup of patients - the "slow virological responders" (positive PCR at week 12 but with less than 6000 IU/mL; negative PCR at week 24) - benefited from the extension of the treatment to 72 weeks, with an SVR of 88%. For patients infected with genotype 4 virus, combination therapy should feature a ribavirin dose of more than 1000 mg/day for an optimal duration of 48 weeks.

14.
Gastroenterol Clin Biol ; 31(2): 185-94, 2007 Feb.
Artigo em Francês | MEDLINE | ID: mdl-17347629

RESUMO

The purpose of this review is to inform physicians about the procedures for compensation of victims of nosocomial or post-transfusion hepatitis C virus infection. The different procedures are described in reference to the legislation and regulations. According to the law dated March 4, 2002 if Hepatitis C is contracted during care, in a private or public hospital, the hospital (and not the physician) is responsible for the damages resulting from the nosocomial infection, except if evidence of another cause is provided. For post-transfusion hepatitis C, the patient must show that a transfusion took place prior to the diagnosis of hepatitis C. The patient must also prove that there were no other sources of infection. The French Institute of Blood can sometimes not be held responsible by proving that none of the donors of the transfused blood were infected with the hepatitis C virus. This is a no fault system. Different examples of litigation show the important role of physicians, who must be aware of the main points of the procedures to better understand what is entailed by the medical certificates which the victim may request and also to provide him with any other steps to be taken to obtain compensation.


Assuntos
Compensação e Reparação/legislação & jurisprudência , Infecção Hospitalar/transmissão , Hepatite C/transmissão , Responsabilidade Legal , Reação Transfusional , Transfusão de Sangue/legislação & jurisprudência , França , Humanos
15.
Eur J Gastroenterol Hepatol ; 18(12): 1321-5, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17099382

RESUMO

Methods for diagnosing hepatic fibrosis have progressed significantly over the last few years--notably with the appearance of minimally invasive biological tests (which avoid the need for liver needle biopsy but nevertheless require a blood sample). Hepatic ultrasonic transient elastography (Fibroscan) is a new diagnostic method for hepatic fibrosis: it is totally noninvasive and gives an immediate result. Here, we review the currently available data on the use of the Fibroscan. Today's main field of application is chronic, viral hepatitis C, with areas under the receiver operation characteristic curve of 0.79-0.83, 0.90-0.91 and 0.91-0.97 for the diagnosis of F2, F3 and F4 fibrosis (defined according to the Metavir classification system), respectively. Furthermore, the Fibroscan enables the noninvasive diagnosis of cirrhosis (regardless of the latter's aetiology), with positive and negative predictive values of 70-95% and 77-95%, respectively. Chronic viral hepatitis B, HIV-hepatitis C virus and HIV-hepatitis B virus coinfections, alcohol-related liver diseases and intrahepatic cholestatic diseases are the device's other main fields of application in hepatology. Today, the Fibroscan is a reliable alternative for the noninvasive diagnosis of hepatic fibrosis. Various diagnostic strategies and performing cost/benefit analyses are now necessary, to assess fully the value of hepatic elastography relative to biological tests for hepatic fibrosis.


Assuntos
Cirrose Hepática/diagnóstico por imagem , Doença Crônica , Elasticidade , Hepatite Viral Humana/diagnóstico por imagem , Humanos , Hepatopatias Alcoólicas/diagnóstico por imagem , Ultrassonografia
16.
Comp Hepatol ; 4: 10, 2005 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-16375767

RESUMO

BACKGROUND: Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system. RESULTS: 310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 - all significantly higher than the standard markers: gamma-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0-5%); 0.58 in grade 2 (6-32%); and 0.74 in grade 3-4 (33-100%). For the diagnosis of grade 2-4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively. CONCLUSION: SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor.

17.
J Clin Pharmacol ; 55(5): 517-24, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25535910

RESUMO

Anemia is a well-known RBV-related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patients on triple therapy had higher ribavirin concentrations at week 12 of treatment (3460 ng/mL vs. 1843 ng/mL; P < .0001). An association was also observed between week 12 eGFR and ribavirin concentration only for patients on triple therapy (P = .002). The proportion of patients with a >20 mL/min/1.73 m(2) decrease in eGFR at week 12 was higher among patients on triple therapy: 32%, 14%, and 5% for boceprevir, telaprevir, and dual therapy, respectively (P = .025 and .026). No correlation was observed between boceprevir and telaprevir concentrations and hemoglobin or eGFR decrease. Exacerbation of anemia in patients on triple therapy is related to higher ribavirin concentrations. We provide an explanation for this increase in plasma RBV concentration. Triple therapy with PEG-IFN, RBV, and telaprevir or boceprevir will remain the only HCV treatment option for many patients. Our data show that the RBV dose can be decreased while maintaining adequate plasma concentrations and reducing anemia.


Assuntos
Anemia/induzido quimicamente , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/sangue , Inibidores de Proteases/uso terapêutico , Ribavirina/sangue , Ribavirina/uso terapêutico , Adulto , Idoso , Antivirais/sangue , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Hemoglobinas/efeitos dos fármacos , Humanos , Interferon-alfa/sangue , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/sangue , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Prolina/sangue , Prolina/uso terapêutico , Inibidores de Proteases/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/administração & dosagem
18.
J Clin Virol ; 31(3): 227-34, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15465417

RESUMO

BACKGROUND: Quantitation of hepatitis C virus (HCV) RNA has become an essential tool for monitoring antiviral therapies in chronically infected patients. Different quantitative HCV RNA assays have been reported, mainly using techniques based on signal amplification with branched DNA (bDNA) technology or target sequence amplification by reverse-transcription PCR method (RT-PCR). OBJECTIVES AND STUDY DESIGN: An RT-PCR assay using TaqMan (fluorescence-based real-time PCR) and minor groove binding (MGB) probes was designed for the quantitative determination of HCV RNA in the clinical samples. Calculation of the concentration of HCV RNA was based on an external standard curve in the presence of an internal positive control (IPC). RESULTS: The assay detected 550 international units (IU)/mL with >95% probability of a positive result, with a linear range extending up to 10,000,000 IU/mL. The test exhibited good reproducibility with intra-assay and inter-assay coefficients of variation (CV) of 1.6% and 3.2%, respectively. All the major HCV genotypes were quantified with equivalent efficiency and accuracy. HCV genotypes 5 and 6 have also been amplified but too few samples have been tested. The performance of this new assay for quantitation of HCV viremia was evaluated with 213 anti-HCV positive sera, 120 of which corresponded to 30 patients sampled during the therapy. We used the Amplicor HCV Monitor assay (Roche Diagnostics, France) and the bDNA VERSANT HCV RNA assay (Bayer Diagnostics, France) to analyze 173 and 40 samples, respectively. The assay described here was significantly correlated with both commercial assays (R2 = 0.9535, P < 0.0001 and R2 = 0.8508, P < 0.0001, respectively). CONCLUSION: The present study illustrated the high reproducibility and reliability of our TaqMan HCV assay. Moreover, the monitoring of viral decline with our assay gave the same results as those obtained with the commercial assays indicating that this new technique provides an attractive approach for measuring HCV viral load.


Assuntos
Hepacivirus/isolamento & purificação , Hepatite C/virologia , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Taq Polimerase , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carga Viral
19.
Antivir Ther ; 17(7): 1311-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22951364

RESUMO

BACKGROUND: Today, treatment of chronic hepatitis C is based on a synergistic combination of pegylated interferon and ribavirin with antiprotease inhibitors. Haemolytic anaemia, which is the major side effect of ribavirin treatment, disrupts ribavirin treatment compliance and varies significantly from one patient to another. There is an individual susceptibility to ribavirin haemolysis. With a view to studying haemolysis, and thus optimizing the treatment response, we have developed a new in vitro tool for analysing the ribavirin-induced lysis of red blood cells. METHODS: Resuspended red blood cells were incubated with isotonic buffer and a range of concentrations of ribavirin. Haemolysis was quantified by spectrophotometric measurement of the supernatant at 540 nm. The assay was used to test the effects of various compounds and to investigate the susceptibility of patients to haemolytic anaemia. RESULTS: In our assay, the degree of haemolysis is dependent on the ribavirin concentration used and can be inhibited by the addition of dipyridamole (50% inhibitory concentration [IC(50)] 30 µM), ATP or glutathione (IC(50) 1.63 mM and 767 µM, respectively). We observed a strong decrease in red blood cell haemolysis in the presence of the ribavirin prodrug viramidine (Taribavirin(®)). When testing the performance of this assay with blood from 24 patients before treatment, we observed a strong correlation between in vitro haemolysis before treatment and the decrease in haemoglobin levels seen in vivo during subsequent treatment (P<0.001). CONCLUSIONS: With this new tool it is possible to better evaluate individual susceptibility to ribavirin-induced haemolysis before the start of treatment. In addition, this model will enable the mechanism of ribavirin-induced anaemia to be further explored and allow molecules that could reduce ribavirin haemolysis to be screened and tested in vitro. This approach could help optimize current and future therapeutic strategies involving ribavirin in the treatment of chronic hepatitis C.


Assuntos
Eritrócitos/efeitos dos fármacos , Hemólise , Ribavirina/efeitos adversos , Trifosfato de Adenosina/farmacologia , Adulto , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/patologia , Dipiridamol/farmacologia , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Glutationa/farmacologia , Testes Hematológicos/métodos , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Concentração Inibidora 50 , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/farmacologia , Poliovirus/efeitos dos fármacos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacologia , Pró-Fármacos/farmacologia , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Ribavirina/administração & dosagem , Ribavirina/análogos & derivados , Ribavirina/farmacologia , Ribavirina/uso terapêutico
20.
PLoS One ; 7(10): e47715, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23082200

RESUMO

BACKGROUND/AIMS: Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/fisiopatologia , Fígado/fisiopatologia , Antivirais/farmacologia , Técnicas de Imagem por Elasticidade , Feminino , Seguimentos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/virologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
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