Biomedical subjects

P Pradat

Publications and source records attributed to P Pradat.

At least 19 recordsLinked to original sources

PubMed2006

Histological benefit of retreatment by pegylated interferon alfa-2b and ribavirin in patients with recurrent hepatitis C virus infection posttransplantation.

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.

Adult↗

PubMed2004

[Hepatitis G virus and labile blood products: role of transfusional transmission].

The GBV-C/HGV (HGV) virus was discovered a few years ago. This virus is known to be parenterally as well as sexually transmitted. However, no study has found some pathogenic roles for HGV so far. In the present study, we aimed to investigate the transmission of HGV by blood components transfused to 284 patients hospitalized in surgery unit in 1995. We tested two parameters of infection in blood components transfused to infected recipients: viral RNA by PCR and anti-E2 antibodies by ELISA. We tried to suspect some potent hepatocyte impacts by assessing the levels of two enzymes in serums: alanine aminotransferase (ALT) and alpha-glutathion S-transferase (alpha-GST). We found that HGV-RNA was detectable in 3.6% of recipients prior to transfusion and 7.5% post-transfusion. For each infected recipient, we retrospectively did a search for HGV-RNA in each transfused blood component, and we found at least one blood component as HGV-RNA-positive for each transfusional infected recipient. Anti-E2 antibody prevalence standing for a former and cured infection was 39.6% in all the recipients. In viremic recipients, ALT levels were mostly normal, while alpha-GST levels were found more commonly elevated than in non-viremic recipients although non-significantly (20% vs. 6.3%; P = 0.07). The present study underlines that HGV transmission is mostly transfusional in surgery units, and that infectiosity of blood components can be anticipated by detection of the viral RNA by PCR. Furthermore, the possible relationship between the serum activity of alpha-GST and the hepatotropism of HGV, although non-admitted as pathogenic, should be investigated.

Aged↗

PubMed2003

The epidemiology of cardiovascular defects, part 2: a study based on data from three large registries of congenital malformations.

There were three objectives of this study: to investigate possible specificity in the association between specific cardiac defects and chromosomal anomalies; to evaluate ways of categorizing cardiac defects into larger groups with epidemiological similarities that could indicate similarities in etiology or pathogenesis; and to analyze the relationship between specific cardiac defects and diabetes. We pooled data on infants (aged 1 year or younger) with congenital cardiovascular defects from three large birth defect registries in California, Sweden, and France. The registries in Sweden and France obtained data through reporting from various sources; in California, medical records were reviewed. For severe congenital heart defects, the percentage of infants with identified chromosomal anomalies varied between 0.9% for d-TGV to 68.4% for ECD. In general, specific cardiac conditions have different risk factors. For example, conotruncal defects have been traditionally grouped, but the data presented in this paper indicates more differences for risk factors for the components of conotruncal defects: tetralogy of Fallot, d-TGV, common truncus, and DORV. In general, we suggest the strategy of "splitting" rather than "lumping" when searching for specific genetic factors and/or teratogens. Adequate analysis thus requires large registries or collaboration among registries. The findings did not support constellations between mothers' diabetes and specific defects.

Abnormalities, Drug-Induced↗

PubMed2003

The epidemiology of cardiovascular defects, part I: a study based on data from three large registries of congenital malformations.

To analyze complex and noncomplex cardiac malformations regarding prevalence and in relation to demographic variables, we pooled data on infants (age 1 year or younger) with congenital cardiovascular defects from three large birth defect registries in California, Sweden, and France. Altogether, 12,932 infants had one or more congenital heart defects out of 4.4 million live births and stillbirths. The registries in Sweden and France obtained data through reporting from various sources; in California, medical records were reviewed. As expected, definitions and ascertained conditions differed among each of the registries. The total rates for severe defects were similar (1.43 per 1,000), but differed for specific defects. Clear differences in epidemiological characteristics existed for specific defects; for example, severe cardiac defects sex ratios were significantly high for hypoplastic left heart syndrome, d-transposition of great vessels, double outlet right ventricle, total anoralous pulmonary venous return, tetralogy of Fallot, and significantly low for pulmonary atresia without ventricular septal defect and endocardial cushion defect. Few defects were similar for several epidemiological characteristics, but, for example, the combination of ventricular and atrial septal defects appeared equivalent with endocardial cushion defect under some circumstances, yet behaved differently with regard to associated noncardiovascular defects.

Age Factors↗

PubMed2003

Clinical relevance of total HCV core antigen testing for hepatitis C monitoring and for predicting patients' response to therapy.

To study the correlation between total Hepatitis C virus (HCV) Core antigen (Ag) and HCV-RNA, and to assess the proficiency of HCV Core Ag testing in monitoring and predicting virologic response during and after pegylated interferon (PEG-IFN) and ribavirin combination therapy. A total of 307 samples from treated and untreated patients were used to assess the correlation between the total HCV Core Ag test and quantitative HCV-RNA assays (Superquant, and Quantiplex branched DNA 2.0 assay). Twenty-four patients received combination therapy for 48 weeks. Blood samples were collected at day 0, and week 2, 4, 12, 24, 48 and 72 for virologic evaluation. A linear relation exists between total HCV Core Ag and HCV-RNA levels. At 3 months the positive predictive value (PPV) of response to therapy was 100% with either HCV Core Ag or HCV-RNA. For HCV Core Ag the negative predictive value (NPV) was 100% whereas for HCV-RNA the NPV was 80% (P > 0.05). At month 1, the PPV was 95% and 100% when determined by HCV Core Ag and HCV-RNA, respectively. The NPV value was 100% for HCV Core Ag and 33% for HCV-RNA (P = 0.005). HCV Core Ag quantification could be useful in clinical practice to predict a sustained virological response early during therapy (4 weeks), reaching an optimal performance at month 3. The determination of total HCV Core Ag levels in serum, constitutes an accurate and reliable alternative to HCV-RNA for monitoring and predicting treatment outcome in patients receiving PEG-IFN/Ribavirin combination therapy.

Antigens, Viral↗

PubMed2003

Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study.

INTRODUCTION: The rate of development of liver fibrosis in hepatitis C virus (HCV) infection varies between individuals. This accounts for the variation in duration of progression to cirrhosis. The aims of this study were: (1) to determine whether fibrosis progresses linearly through the grading scales and (2) to identify factors which influence the rate of fibrosis. METHODS: HCV infected patients who had undergone at least one liver biopsy were identified. Biopsies were scored using the modified HAI (Ishak) and METAVIR systems, which were compared. Patients were treatment naïve at first biopsy. Demographic features were examined for their relationship to fibrosis rate (defined as fibrosis stage/infection duration) using univariate and multivariate analysis. A subgroup of patients with two biopsies was examined to test the assumption that fibrosis progresses in a linear fashion. RESULTS: A total of 917 patients were included. Male sex (p<0.00001), older age at infection (p</=0.00001), and viral genotype non-1 (p=0.005) were all associated with a rapid rate of fibrosis. On multiple linear regression they accounted for 29.5% of the variability in fibrosis rate (r(2)=0.295). METAVIR and Ishak scores were highly correlated (r=0.935, p<0.0001). In 137 patients who had two biopsies, the predicted probability for an increase of 1 on the fibrosis score was too low to assess linearity. CONCLUSIONS: Demographic features account for a minority of fibrosis rate variability. The Ishak and METAVIR scoring systems are equivalent. Linearity of fibrosis progression cannot be assessed in biopsies only a few years apart.

Adult↗

PubMed2001

Prevalence of hepatitis C infection among general practice patients in the Lyon area, France.

STUDY OBJECTIVE: To estimate the prevalence of hepatitis C virus (HCV) infection among patients in general practices. DESIGN AND PARTICIPANTS: A screening campaign requested by the French Health Insurance Fund and involving 271 general practitioners (GPs) and 96% of the 95 medical laboratories was conducted in the Lyon area. Each GP participated for one week and offered an HCV screening to all patients aged 18-69 years during this period. Risk factors were estimated by a medical questionnaire (MQ) filled in by the physician. MAIN RESULTS: From May to October 1997, 11,805 subjects were recruited into the study. Among them, 101 were known HCV positive. The MQ was filled up in 86% of the 11,704 remaining patients. Only 59% of those (6876/11,704) went to a laboratory to be tested. Fifty-one were ELISA positive of whom 30 were confirmed by RIBA or PCR. If we add 101 patients that were known HCV positive and estimate the prevalence among patients who did not go to the laboratory, this study gives a total estimated prevalence of 1.3%. CONCLUSIONS: The prevalence of HCV infection among patients of GPs is about 1.3%, very close to the estimate in the French general population. The substantial number of patients known HCV positive is probably related to the participation of GPs sensitised to HCV issues and who already have screened most of their HCV patients.

Adolescent↗

PubMed2001

[Medical follow-up of patients with positive serology for hepatitis C virus].

OBJECTIVE: A screening campaign requested by the French Health Insurance Fund was performed in the Lyon area to access the prevalence of anti-hepatitis C virus in patients from 271 general practitioners and to observe the follow-up of the patients with had positive serology. A total of 101 patients had already had hepatitis C virus antibodies and 30 patients had newly detected antibodies against hepatitis C virus. All subject received appropriate medical care. The aim of this study was to analyse medical follow-up. METHODS: Follow-up was performed for one year by the patient's general practitioner or a specialist of liver disease. Clinical, biological, histological and virological data were collected and treatment was proposed when appropriate. Information was gathered anonymously by phone. RESULTS: Follow-up was regular for 28 patients (93%). During this follow-up, ALAT levels remained within the normal limit for 13 patients (43%) and 6 of them had undetectable viral RNA by PCR. In the other patients (50%), a liver biopsy was affered to 11 patients (40%), and performed in 9 (30%). Treatment was started in 8 patients. CONCLUSION: The results of this study on medical follow-up are satisfying. The general practitioner plays a key role in the follow-up of patients infected by hepatitis C virus.

Adolescent↗

PubMed2000

Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity.

BACKGROUND/AIMS: We aimed to clarify the clinical relevance of hepatitis B virus pre-core mutant detection in patients with chronic hepatitis B using a newly developed assay. METHODS: Viral genotypes and pre-core mutations were studied in relation to viral persistence and liver disease severity using INNO-LiPA methodology. The study group included 151 patients with chronic hepatitis B, 85 positive for HBeAg (group I) and 66 positive for anti-HBe (group II). RESULTS: The prevalence of viral genotypes in group I was: 64% A, 1% B, 15% C, 19% D, 0% E, 0% F and in group II: 39% A, 0% B, 2% C, 56% D, 2% E, 2% F (p<0.001). The prevalence of mutations at pre-core codon 28 (M2) was lower in group I (5%) than in group II (64%) (p<0.001). The prevalence of pre-core promoter mutations was also lower in group I (21%) than in group II (61%) (p<0.001). M2 mutations were more frequently detected in genotype D than in genotype A (p<0.001), while the other mutations were not influenced by viral genotype. Serum HBV DNA levels were significantly lower in group II versus group I (p<0.001), and in patients with any of the pre-core mutations versus wild-type sequence (p<0.01). Although cirrhosis was more frequent in group II (37%) versus group I (22%) and in patients with either one of the pre-core mutation (31%) versus wild-type sequence (25%), there was no statistical difference in liver severity assessed by ALT levels and Knodell score. CONCLUSION: Pre-core mutants, whose molecular pattern is strongly dependent on viral genotypes, are associated with viral persistence in anti-HBe positive patients with ongoing chronic hepatitis B. The availability of this rapid assay should allow a precise monitoring of viral pre-core mutants during the course of chronic hepatitis B.

Adolescent↗

PubMed2000

Impact of hepatitis C virus infection on healthy subjects on an Italian island.

Field studies in large numbers of subjects unselected for risk factors are needed to assess the true prevalence and health burden of hepatitis C virus (HCV) infection. We assessed the prevalence, virological characteristics, risk factors and evidence of liver disease in a population of healthy subjects from an urban area of Sardinia. Hepatitis B virus (HBV) markers were also studied. The prevalence of antibodies to HCV (anti-HCV) (recombinant immunoblot assay [RIBA]-confirmed positive results) was 3.19% in 3324 workers and 7.11% in 225 elderly subjects, with a cumulative anti-HCV prevalence of 2.70% (95% CI 2.17-3.24). Males were more frequently positive than females (P < 0.01). The age-specific prevalence of HCV infection increased progressively in females. It showed two peaks in males: one in the fourth decade, the other in the seventh decade. HCV RNA was detected in 63.16% of the RIBA-positive sera, in 10% of the RIBA indeterminates and in none of the RIBA-negative specimens. Only 1.75% of anti-HCV-positive subjects had elevated transaminases. The frequency of HCV genotype 1b was 32.79%; of 1a, 21.31%; of 3a, 19.67%; of 4, 13.11%; and of 2a, 13.11%. HBV markers were found in 28.03% of workers. On multivariate analysis, male gender and tattooing were significantly associated with HCV and HBV infections: transfusion and travel with HCV, and age over 40 with HBV. The age prevalence rates of HCV infection in the Cagliari area reflect different risk factors that have been operative at different times. In this urban area, the large majority of HCV infections run a subclinical course.

Adolescent↗

PubMed2000

Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy.

To compare three quantitative assays measuring viral load in patients with chronic hepatitis C and to determine their value in predicting response to interferon (IFN) therapy, we analysed serum from 896 patients from eight European Centres using QUANTIPLEXtrade mark bDNA, MONITOR AMPLICORtrade mark and SUPERQUANTtrade mark assays. Analyses were performed on the same sample. Viral genotype was assessed using INNO-LiPA HCV II kits. Intercentre variations were observed that were related to the handling of specimens not processed and stored within 6 h of blood sampling. Among sera with optimal handling, a stronger correlation was observed between bDNA and SUPERQUANT (0.806) than between bDNA and MONITOR (0.677) and between MONITOR and SUPERQUANT (0.632). These discrepancies were greatest with genotype 2 (bDNA/SUPERQUANT= 0.772; bDNA/MONITOR=0. 456; SUPERQUANT/MONITOR= 0.299). This correlation was influenced by viraemia level and was better at lower viral loads. The proportion of sera with undetectable viral load was 15% with bDNA, 9.7% with MONITOR and 7.7% with SUPERQUANT. For the three measurements, the best cut-offs of sustained response to IFN treatment were located at their detection threshold. Among patients with viral load below the detection level, a sustained response was observed in 35% tested with bDNA, 38% with MONITOR and 80% with SUPERQUANT. Hence a stronger correlation was observed between bDNA and SUPERQUANT than between either of these assays and MONITOR. SUPERQUANT was the most sensitive assay and this greater sensitivity was associated with a better predictive value of treatment response.

Antiviral Agents↗

PubMed2000

HCV: epidemiology, modes of transmission and prevention of spread.

Approximately 3% of the world's population has been infected with the hepatitis C virus (HCV), which represents about 170 million chronic carriers at risk of developing serious complications. Following the introduction of screening of blood donors for infection the risk of transmitting HCV by blood products is presently at 1/200,000 units distributed. Intravenous (i.v.) drug users are currently the main risk group with a prevalence rate of about 80% and a yearly incidence varying between 4 and 6%. Vertical and sexual transmissions have also been implicated but data are limited and sometimes controversial. The source of infection for the 30% of cases without an identifiable risk factor remains to be clarified. Prevention of spread includes detailed information of persons at risk of being infected, screening of high-risk populations, strengthening of syringe exchanges among i.v. drug users and strict application of disinfection procedures for all invasive medical equipment.

Disease Transmission, Infectious↗

PubMed2000

Epidemiology of hepatitis C virus infection in seven European Union countries: a critical analysis of the literature. HENCORE Group. (Hepatitis C European Network for Co-operative Research.

Hepatitis C is now recognized as the most common infection causing chronic liver disease in the European population. Our aim was to assess the prevalence of the antibody to hepatitis C virus (HCV), and the incidence of HCV seroconversion in the general population and the main risk groups, namely intravenous drug users, haemodialysis and transfused patients, in seven countries of the European Union, by carrying out a critical analysis of the literature. Data sources used were the Medline database and a manual search using the key words: hepatitis C, prevalence, incidence, transmission, risk factors and epidemiology. Articles published between January 1990 and March 1997 were reviewed. Articles were reviewed according to a critical analysis method regarding title, type of article, study design, period and population, tests, results and their consistency with data. The tests performed were mainly second- or third-generation serological tests. The average prevalence rate in blood donors was 1%, with a north-south gradient ranging from 0.04% to 2%. Prevalence varied from 20% to 30% in haemodialysis patients. The incidence in transfused patients was less than 1% after 1991. The prevalence in intravenous drug users was about 80%. Multicentre studies conducted in larger samples are needed to obtain more accurate and reliable results, in particular. However, the epidemiological studies available allowed us to assess the magnitude of HCV infection in Europe.

Europe↗

PubMed1999

Hepatitis C virus infection in Western Europe.

Hepatitis C virus (HCV) infection is now recognised as the most common infection causing chronic liver disease in Europe. Approximately 3% of the world population has been infected with HCV, which represents about 170 million chronic carriers at risk of developing serious complications with more than 5 million in Europe alone. In the general population, the prevalence varies geographically from about 0.5% in northern countries to 2% in Mediterranean countries. Among newly detected HCV cases, 40-60% have normal ALT levels, 80% are viraemic, while about 70% of newly detected HCV carriers present histologic liver disease. More than 75% of the cases remain to be identified. The residual risk for transmitting HCV by blood products is at present 1/200 000 units distributed. Intravenous drug users are currently the main risk group. The prevalence rate is about 80% and the yearly incidence varies between 4 and 6%. In haemodialysis patients, the prevalence ranges from 10% to 30% and the incidence from 3% to 7%. The source of infection for the 30% of cases without identifiable risk factor remains to be clarified and appropriate well-controlled case-control studies on large samples are necessary. Further training and information campaigns remain desirable to improve knowledge and awareness among health care professionals.

Europe↗

PubMed1999

Viral hepatitis.

Hepatitis A is still the most frequently reported vaccine preventable disease. A reduction in the incidence will only be achieved by routine childhood vaccination rather than by targeted vaccination of high-risk groups. A larger vaccine program is warranted. Hepatitis B remains a large public health problem. Vaccination targeted to high-risk adults failed to decrease the incidence of hepatitis B virus (HBV) infection. Sexual as well as nosocomial transmission remain serious problems. Vaccine escape variants have also been identified in newborns from infected mothers who had been vaccinated at birth. Clearance of HBV infection results from complex immune mechanisms including TH1 cytokines significantly associated with HLA class II alleles. Escape HBV mutants, especially precore mutants, influence the outcome. The sequences of the promoter and other critical regions were associated with severe activity. Lamivudine is a major advance in therapy of chronic hepatitis B which was recently approved in many countries. Although drug resistant mutants may be selected during therapy, additional nucleoside analogues including adefovir are promising. Optimal combination strategies of different active compounds need to be researched. Three per cent of the world population has been infected with hepatitis C virus (HCV). Epidemiology has shifted from transfusion to non-transfusion settings. Intravenous drug abuse is currently the main risk but nosocomial infection is also of concern. Three independent factors seem associated with fibrosis progression: age, daily alcohol consumption of 50 g or more and male gender. Median duration of progression to cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per year develop hepatocellular carcinoma. There is little evidence that direct cytopathicity plays a significant role in liver cell injury. HCV also infects extrahepatic cells which seems critical in the pathogenesis of the many extrahepatic manifestations. The recent identification of CD81 protein as one of the HCV receptor candidates may help us to understand how chronic HCV infection may trigger a wide spectrum of clinical manifestations, autoimmune or even lymphoproliferative, through potent continuous B cell activation in the context of various host and/or environmental cofactors. Direct measurement of HCV RNA has clarified HCV replication kinetics and variability. Among patients with chronic hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a response rate of 28% among those with genotype 1 and 66% with other genotypes. Similar differences were found for combination therapy among patients who had relapsed following previous interferon (IFN) therapy. Viral load prior to treatment has been clearly shown to be predictive of response to interferon treatment, with increased viral load associated with decrease rates of response. In patients non-responsive to interferon, a second course of interferon alone has no beneficial effect whereas combination therapy may induce response in 25%. In conclusion, combination therapy should be given in all situations. Viral eradication should not be the only objective of the treatment since histological improvement may be obtained despite persisting viral replication with prolonged maintenance of antiviral therapy.

Journal Article↗

PubMed1995

[Pheochromocytoma in Von Hippel Lindau disease. 3 cases].

Presenting 3 personally examined cases, the authors underline the incidence and the characteristics of pheochromocytoma associated with Von Hippel Lindau disease. In conclusion, a systematic screening for Von Hippel Lindau disease-often unrecognized to day-must be done in every patient presenting with pheochromocytoma.

Adrenal Gland Neoplasms↗

PubMed1994

Recurrence risk for major congenital heart defects in Sweden: a registry study.

During the period 1981-1986, 1605 infants presenting a major congenital heart defect (CHD) were identified in Sweden. Using the personal identification numbers of the mothers, 1507 of them could be linked to the Medical Birth Registry and two controls were selected for each infant. For this total of 4521 infants, 2686 postoccurrence sibs born during the period 1981-1989 were identified from the Medical Birth Registry. The tendency to have one or more sibs was higher among cases than among controls and was correlated to the life status of the proband. This tendency did not vary according to the type of CHD when controlling for life status. The prevalence at birth of CHD was almost four times higher among sibs of CHD infants than among sibs of normal infants. The tendency to have a sib with an extracardiac malformation did not differ between CHD probands and normal probands. The importance of only including births occurring after the proband when evaluating recurrence risks is stressed.

Family Health↗

PubMed1993

The epidemiology of three serious cardiac defects. A joint study between five centres.

The paper reports a joint study made by five member programs of the International Clearinghouse for Birth Defects Monitoring Systems. Three specific heart malformations were studied, hypoplastic left heart syndrome (HLHS), transposition of the great vessels (TGV), tetralogy of Fallot, and some epidemiological characteristics were analyzed. The prevalence at birth was estimated to be 2.0, 2.9, and 2.2 per 10,000 births, respectively. No time trend in the prevalence at birth was observed for any one of the three malformations in the total study population. When only isolated defects were considered (infants without major non-cardiac malformations), all three cardiac anomalies showed an increased rate in infants with low birth weight, short gestational duration and probably twinning. A preponderance for males was observed for each defect but was strongest among infants with tetralogy of Fallot (sex ratio 2.5 for Fallot, 1.4 to 1.5 for the other conditions). There were also differences between the three cardiac defects with respect to percentage of low birth weight, preterm births, and rate and type of associated extracardiac malformations. This paper stresses the advantage of pooling data from different registries in studies of uncommon specific malformations and infrequent characteristics.

Adult↗