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1.
Liver Int ; 42(6): 1386-1400, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35025128

RESUMEN

BACKGROUND AND AIMS: Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients. METHODS: We used two prospective cohorts of Child-Pugh A cirrhosis due to either alcohol or viral hepatitis. Primary end point was the cumulated incidence of 'Decompensation' at 3 years, defined as the occurrence of ascites , hydrothorax, encephalopathy, gastrointestinal bleeding related to portal hypertension, or bilirubin >45 µmol/L. Secondary end points were the cumulated incidences of (1) 'Disease Progression' including a « decompensation¼ or « the occurrence of one or more parameters ¼ among: prothrombin time (PT) <45%, albumin <28 g/L, Child-Pugh worsening (B or C vs A or B, C vs B), hepatorenal syndrome, and hepato-pulmonary syndrome, (2) other events such as non-malignant portal vein thrombosis (nmPVT), and (3) overall survival. RESULTS: Patients (n = 1789; 59.9% Non-O group; 40.1% group O) were followed during a median of 65.4 months. At 3 years cumulated incidence of Decompensation was 8.3% in Non-O group and 7.2% in group O (P = .27). Cumulated incidence of Disease Progression was 20.7% in Non-O group and 18.9% in group O (P = .26). Cumulated incidence of nmPVT was 2.7% in Non-O group and 2.8% in group O (P = .05). At 3 years overall survival was 92.4% in Non-O group and 93.4% in group O (P = 1). CONCLUSION: Non-O group does not influence disease outcome in Child-Pugh A cirrhotic patients. Clinicals trial number NCT03342170.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Hipertensión Portal , Progresión de la Enfermedad , Humanos , Hipertensión Portal/complicaciones , Cirrosis Hepática , Estudios Prospectivos
2.
J Hepatol ; 73(6): 1434-1445, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32615276

RESUMEN

BACKGROUND & AIMS: Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status. METHODS: Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012-01/2014). RESULTS: Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]. CONCLUSIONS: Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs. LAY SUMMARY: Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.


Asunto(s)
Carcinoma Hepatocelular , Reglas de Decisión Clínica , Hepatitis C/complicaciones , Cirrosis Hepática , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Análisis Costo-Beneficio , Femenino , Francia/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo/economía , Medición de Riesgo/métodos , Vigilancia de Guardia
3.
Gastroenterology ; 156(4): 997-1009.e5, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30768988

RESUMEN

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.


Asunto(s)
Várices Esofágicas y Gástricas/diagnóstico por imagen , Cirrosis Hepática/fisiopatología , Tamizaje Masivo/normas , Vigilancia de la Población , Guías de Práctica Clínica como Asunto , Antivirales/uso terapéutico , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad , Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/etiología , Femenino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Tasa de Supervivencia , Respuesta Virológica Sostenida
4.
Gastroenterology ; 155(6): 1816-1827.e9, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30144431

RESUMEN

BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis. METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up. RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.


Asunto(s)
Antibacterianos/administración & dosificación , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/mortalidad , Norfloxacino/administración & dosificación , Ascitis/etiología , Ascitis/mortalidad , Método Doble Ciego , Femenino , Francia/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Humanos , Incidencia , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
5.
Gastroenterology ; 155(5): 1436-1450.e6, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30031138

RESUMEN

BACKGROUND & AIMS: Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). METHODS: Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. RESULTS: Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73). CONCLUSIONS: Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.


Asunto(s)
Antivirales/efectos adversos , Carcinoma Hepatocelular/epidemiología , Hepatitis C/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/epidemiología , Anciano , Carcinoma Hepatocelular/etiología , Femenino , Hepatitis C/virología , Humanos , Incidencia , Interferones/uso terapéutico , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
6.
Gastroenterology ; 155(2): 431-442.e10, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29729258

RESUMEN

BACKGROUND & AIMS: Semi-annual surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. We aimed to determine how compliance with HCC surveillance guidelines affects survival times of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis who developed HCC. METHODS: We collected data from the prospective ANRS CO12 CirVir study, from March 2006 through June 2012, on 1671 patients with biopsy-proven viral cirrhosis and no previous liver complications who were undergoing surveillance for HCC at 35 centers in France. Only 216 patients who developed HCC during the follow-up period were included in the analysis. Patients were considered to be compliant with surveillance guidelines if the time between their last surveillance image evaluation and diagnosis of HCC were fewer than 7 months and noncompliant if this time was 7 months or longer. RESULTS: HCC was detected in 216 patients, at a median follow-up time of 59.7 months. Of these patients, 140 (80.5%) were Barcelona Clinic Liver Cancer stage 0/A, 135 (69.9%) received first-line curative treatment (15 underwent transplantation, 29 underwent resection, 89 received percutaneous ablation, and 2 received resection and percutaneous ablation), and 129 (60.0%) were compliant with surveillance guidelines. Seventy-nine of the patients with HCC died; 49 deaths were associated with tumor progression. After lead-time adjustment, overall survival (OS) time was longer in patients compliant with surveillance guidelines (median OS time, 53.2 months) than noncompliant patients (median OS time, 25.4 months) (P = .0107); this difference remained significant even when we changed lead time assumptions. In multivariate analysis adjusted for a propensity score, compliance with HCC surveillance guidelines was associated with low tumor burden, allocation of curative treatment, and increased OS time compared with noncompliance (hazard ratio for OS, 2.19; 95% confidence interval, 1.16-4.14; P = .0150). CONCLUSIONS: In an analysis of data from the ANRS CO12 CirVir cohort, we associated compliance with HCC surveillance guidelines (fewer than 7 months between image evaluations) with early diagnosis, allocation of curative treatment, and longer adjusted OS of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis and a diagnosis of HCC.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Detección Precoz del Cáncer/normas , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidad , Anciano , Antivirales/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virología , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Francia/epidemiología , Adhesión a Directriz/estadística & datos numéricos , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Estimación de Kaplan-Meier , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/terapia , Cirrosis Hepática/virología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Guías de Práctica Clínica como Asunto , Estudios Prospectivos
7.
J Viral Hepat ; 26(3): 384-396, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30380181

RESUMEN

Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicentre prospective cohort of HBV cirrhotic patients. Patients with biopsy-proven Child-Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C coinfection were selected for: (a) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; (b) HBsAg quantification using baseline and sequential 2-year frozen sera; (c) baseline HBV genotype determination; and (d) assessment of risk factors and applicability of HCC risk scores (Kaplan-Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3% and baseline detectable HBV DNA in 88 patients), the baseline and 2-year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow-up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age > 50 years, platelets ≤ 150 × 103 /mm3 and body mass index ≥ 30 kg/m2 . Two out of five risk scores were validated, and the most accurate was PAGE-B at 1 year. Moreover, HCC in patients without maintained virological suppression seems more aggressive and less accessible to curative treatment. In conclusion, in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host-related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE-B score was the most accurate risk score.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/etiología , Hepatitis B/tratamiento farmacológico , Cirrosis Hepática/virología , Neoplasias Hepáticas/etiología , Respuesta Virológica Sostenida , Femenino , Genotipo , Hepatitis B/complicaciones , Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios
8.
Hepatology ; 68(4): 1245-1259, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29663511

RESUMEN

Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy-proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child-Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5-year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time-dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV-HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow-up of 59.7 months, 227 PLCs were diagnosed (5-year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5-year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04-1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08-2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication. CONCLUSION: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018).


Asunto(s)
Carcinoma Hepatocelular/virología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Neoplasias/mortalidad , Adulto , Anciano , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Bases de Datos Factuales , Progresión de la Enfermedad , Femenino , Francia , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/fisiopatología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/virología , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Análisis de Supervivencia
9.
Gastroenterology ; 152(1): 142-156.e2, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27641509

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepatitis C/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Neoplasias Hepáticas/epidemiología , Respuesta Virológica Sostenida , Anciano , Aspartato Aminotransferasas/sangre , Infecciones Bacterianas/epidemiología , Índice de Masa Corporal , Carcinoma Hepatocelular/mortalidad , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Femenino , Estudios de Seguimiento , Francia/epidemiología , Hepatitis C/complicaciones , Hepatitis C/mortalidad , Humanos , Incidencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidad , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Tiempo de Protrombina , gamma-Glutamiltransferasa/sangre
10.
Am Heart J ; 198: 4-17, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29653647

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/virología , Distribución por Edad , Anciano , Antivirales/uso terapéutico , Biopsia con Aguja , Enfermedades Cardiovasculares/terapia , Estudios de Cohortes , Femenino , Francia , Hepatitis C Crónica/fisiopatología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Cirrosis Hepática/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Tasa de Supervivencia
11.
Gut ; 66(2): 330-341, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-26511797

RESUMEN

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.


Asunto(s)
Infecciones Bacterianas/mortalidad , Coinfección/mortalidad , Cirrosis Hepática/mortalidad , Cirrosis Hepática/fisiopatología , Neoplasias Hepáticas/mortalidad , Adulto , Causas de Muerte , Femenino , Francia/epidemiología , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Incidencia , Cirrosis Hepática/virología , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Peritonitis/microbiología , Peritonitis/mortalidad , Neumonía/mortalidad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Infecciones Urinarias/mortalidad
12.
Hepatology ; 64(4): 1136-47, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27348075

RESUMEN

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).


Asunto(s)
Carcinoma Hepatocelular/etiología , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Nomogramas , Carcinoma Hepatocelular/epidemiología , Femenino , Humanos , Cirrosis Hepática/virología , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos
13.
Nephrol Dial Transplant ; 32(12): 2065-2071, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-27760839

RESUMEN

BACKGROUND: Chronic hepatitis C virus (HCV) infection is the most common chronic liver disease in patients with end-stage renal disease (ESRD). Over the last few years, second-generation direct-acting antivirals have been revolutionary in the treatment of hepatitis C, and sofosbuvir (SOF) is the backbone of most modern treatment strategies. Since SOF is eliminated through the kidney, the aim of this multicentre retrospective study was to assess its antiviral efficacy and safety in HCV-infected patients with severe renal failure [including haemodialysis (HD) patients]. METHODS: Fifty patients (36 males, mean age ± standard deviation 60.5 ± 7.5 years) with chronic HCV infection (G1: 28/56%, cirrhosis: 27/54%) and severe renal failure [i.e. MDRD estimated glomerular filtration rate (eGFR) <35 mL/min], including 35 on HD, were enrolled. Antiviral treatment consisted of SOF/ribavirin (RBV) (n = 7), SOF/RBV/pegylated interferon (n = 2), SOF/daclatasvir ± RBV (n = 30) or SOF/simeprevir ± RBV (n = 11) for 12 or 24 weeks. A reduced dose of SOF (400 mg three times a week or 400 mg every other day) was given to all HD patients. Initial dose of RBV (n = 12) ranged from 400 to 4200 mg/week. RESULTS: On an intent-to-treat-based analysis, sustained virological response rate was 86% at 12 weeks. During therapy, haemoglobin levels were not significantly modified, but recombinant erythropoietin (rEPO) dose significantly increased in patients treated with RBV. Two patients (4%) required blood transfusion. No patient had treatment discontinuation due to side effects. Dose of RBV was reduced in two patients (16.7%) during antiviral therapy. Dose of SOF was reduced in two non-HD patients because of side effects. In non-HD patients, median eGFR was not significantly modified during treatment. CONCLUSIONS: Our results strongly suggest that SOF-based antiviral therapy, with a reduced dose of SOF, is safe and effective for the treatment of HCV patients with ESRD, including HD patients.


Asunto(s)
Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Insuficiencia Renal/complicaciones , Sofosbuvir/uso terapéutico , Antivirales/uso terapéutico , Femenino , Tasa de Filtración Glomerular , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal/virología , Estudios Retrospectivos
14.
Hepatology ; 62(3): 737-50, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25678021

RESUMEN

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.


Asunto(s)
Carcinoma Hepatocelular/virología , Causas de Muerte , Cirrosis Hepática/mortalidad , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Adulto , Análisis de Varianza , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/fisiopatología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Francia , Hepatitis B/complicaciones , Hepatitis B/patología , Hepatitis C/complicaciones , Hepatitis C/patología , Humanos , Cirrosis Hepática/complicaciones , Fallo Hepático/mortalidad , Fallo Hepático/patología , Fallo Hepático/virología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Análisis de Supervivencia
15.
J Hepatol ; 62(5): 1047-55, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25596313

RESUMEN

BACKGROUND & AIMS: Simeprevir (SMV) is a once-daily (QD), oral hepatitis C virus (HCV) NS3/4A protease inhibitor approved for treatment of genotype (GT) 1 and GT4 infection. This Phase III, open-label, single-arm study (RESTORE; NCT01567735) evaluated efficacy/safety of SMV with peginterferon-α-2a/ribavirin (PR) in patients with chronic HCV GT4 infection. METHODS: 107 patients were included. Treatment-naïve (n=35) and prior relapse patients (n=22) received SMV 150mg QD+PR (12 weeks), followed by PR alone (12 or 36 weeks, response-guided [HCV RNA <25IU/ml detectable/undetectable at week 4 and <25IU/ml undetectable at week 12]). Prior non-responders (partial, n=10; null, n=40) received SMV/PR (12 weeks), followed by PR for 36 weeks. The primary endpoint was sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS: Median age: 49.0years; 28.0% Black/African; 7.5% IL28B CC; 28.8% METAVIR F4. Overall, 65.4% (70/107) of patients achieved SVR12 (82.9% [29/35] treatment-naïve; 86.4% [19/22] prior relapsers; 60.0% [6/10] prior partial responders; 40.0% [16/40] prior null responders). In treatment-naïve and prior relapser patients fulfilling response-guided criteria for 24 weeks of treatment (88.6% [31/35] and 90.9% [20/22]), SVR12 rates were high: 93.5% [29/31] and 95.0% [19/20], respectively. Overall on-treatment failure and relapse rates were 23.4% (25/107) and 14.6% (12/82), respectively. Adverse events (AEs) were mainly grade 1/2; serious AEs were infrequent (4.7%) and considered unrelated to SMV. CONCLUSIONS: Efficacy and safety of SMV 150mg QD for 12 weeks with PR in treatment-naïve or -experienced patients with chronic HCV GT4 infection were in line with previous reports for HCV GT1 infection.


Asunto(s)
Hepacivirus , Hepatitis C Crónica , Interferón-alfa , Polietilenglicoles , Ribavirina , Simeprevir , Antivirales/administración & dosificación , Antivirales/efectos adversos , Esquema de Medicación , Quimioterapia Combinada/métodos , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/etnología , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , ARN Viral/análisis , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Prevención Secundaria , Simeprevir/administración & dosificación , Simeprevir/efectos adversos , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Carga Viral/métodos
16.
Blood ; 116(16): 2875-83, 2010 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-20551378

RESUMEN

Chelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus- or hepatitis C virus-related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical management of chronic liver disease in thalassemia patients is a team management issue requiring a multidisciplinary approach. The purposes of this paper are to summarize the knowledge on the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy in thalassemia patients with chronic hepatitis B or C virus or cirrhosis.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Talasemia/complicaciones , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/transmisión , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/transmisión , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Talasemia/tratamiento farmacológico , Talasemia/epidemiología
17.
J Virol Methods ; 154(1-2): 1-6, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18929599

RESUMEN

The quantitation of human hepatitis B virus (HBV) in the serum of infected patients is recommended to characterize the course of chronic HBV infection. The aim of this prospective study was to evaluate the performance of the Abbott RealTime PCR assay for HBV DNA quantitation by comparison with the standard Versant HBV DNA 3.0 assay. The better sensitivity and broader dynamic range of HBV DNA quantitation using the Abbott RealTime PCR assay was confirmed by the study of 362 serum samples from 311 patients. In addition, data analysis revealed the concordance of HBV DNA quantitations between the two assays. When this evaluation was assessed as a function of HBV genotype, there was discordance for HBV genotype C samples. Thus, we performed an in-house PCR to confirm the discrepancy observed regarding the HBV genotypes. The in-house PCR results agreed better with the Abbott RealTime PCR method when compared with the standard hybridization assay. In conclusion, the wide dynamic range of HBV DNA quantitation achieved with the Abbott RealTime PCR assay makes it appropriate for the clinical monitoring of HBV infected patients. However, a change of HBV DNA quantitation method could influence results on the follow-up of HBV genotype C infected patients.


Asunto(s)
ADN Viral/sangre , ADN Viral/genética , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Carga Viral , Genotipo , Humanos , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , Sensibilidad y Especificidad
18.
Eur J Gastroenterol Hepatol ; 30(10): 1216-1223, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29727379

RESUMEN

BACKGROUND: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC. PATIENTS AND METHODS: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013. RESULTS: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P<0.001), but not for Child-Pugh A (33.3%) or B patients (25.0%). A Child-Pugh score of above C10 was the best predictor of in-hospital mortality. In LC, Child-Pugh score (odds ratio=1.5; 95% confidence interval: 1.2-2.0; P=0.002) and history of decompensation (odds ratio=3.1; 95% confidence interval: 1.1-9.0; P=0.003) were independent predictive factors for in-hospital mortality. CONCLUSION: Severe liver failure but not cirrhosis is the strongest predictive factor of mortality related to IE in LC. Use of aminosides and rifamycin should be reassessed in LC, and cardiac surgery should be considered for selected patients.


Asunto(s)
Endocarditis Bacteriana/mortalidad , Cirrosis Hepática/mortalidad , Fallo Hepático/mortalidad , Anciano , Procedimientos Quirúrgicos Cardíacos , Estudios de Casos y Controles , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Francia/epidemiología , Cardiopatías/epidemiología , Mortalidad Hospitalaria , Humanos , Cirrosis Hepática/complicaciones , Fallo Hepático/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Suiza/epidemiología
19.
Clin Gastroenterol Hepatol ; 5(4): 502-7, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17261383

RESUMEN

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.


Asunto(s)
Hepatitis C Crónica/mortalidad , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/mortalidad , Cirrosis Hepática/virología , Anciano , Antivirales/uso terapéutico , Intervalos de Confianza , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Probabilidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteínas Recombinantes , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
20.
IDCases ; 8: 54-62, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28417069

RESUMEN

We report two cases of bacteremia due to Clostridium difficile from two French hospitals. The first patient with previously diagnosed rectal carcinoma underwent courses of chemotherapy, and antimicrobial treatment, and survived the C. difficile bacteremia. The second patient with colon perforation and newly diagnosed lung cancer underwent antimicrobial treatment in an ICU but died shortly after the episode of C. difficile bacteremia. A review of the literature allowed the identification of 137 cases of bacteremia between July 1962 and November 2016. Advanced age, gastro-intestinal disruption, severe underlying diseases and antimicrobial exposure were the major risk factors for C. difficile bacteremia. Antimicrobial therapy was primarily based on metronidazole and/or vancomycin. The crude mortality rate was 35% (21/60).

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