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D Ouzan

Publications and source records attributed to D Ouzan.

At least 19 recordsLinked to original sources
PubMed2006

Multicentre study of hepatitis B virus genotypes in France: correlation with liver fibrosis and hepatitis B e antigen status.

The clinical significance of hepatitis B virus (HBV) genotypes is still under debate. The aims of this study were to assess the distribution of HBV genotypes in France and to identify the associations between HBV genotypes and patient demographics, severity of liver disease and HBeAg status in patients referred to tertiary care centres. This was a French, multicentre, retrospective study on 262 patients with chronic HBV infection. HBV genotypes were determined using INNO-LiPA. Liver fibrosis damage was evaluated by histological analysis of biopsy samples. Patients were mainly male (74%), of Caucasian (65%), Asian (17%) or African (18%) ethnicity and 36% were HBeAg positive. All A-G genotypes were found, the most frequent being genotypes D (27%) and A (24%), followed by E (13%) and C (12%), and B (7%). Mixed genotypes were detected in 16% of the cases. Genotype A was associated with sexual contact (P < 0.001) and genotype D with transfusion (P < 0.001) and HBe antibody positivity (P = 0.03).The distribution of HBV genotypes differed with regard to the ethnicity, and may reflect migration patterns. Genotypes A and D were the most frequent in France. Genotype A was associated with HBeAg positivity and genotype D with HBe antibody positivity. In our European patients, we find no clear association between a given HBV genotype and liver disease severity.

Adult↗
PubMed2006

Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies.

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).

Adult↗
PubMed2005

Management of chronic hepatitis C in French departments of internal medicine and infectious diseases.

This prospective, multicentre study was conducted during 2-30 April 2001 in the internal medicine/infectious diseases services in France and included data from 1858 hepatitis C virus (HCV)-infected patients, half of whom were HIV co-infected. The aims were to outline the type of pre-therapeutic evaluation of HCV infection performed (HCV RNA, genotype, liver biopsy); determine the proportion and characteristics of patients receiving antiviral treatment; and determine if any changes in these parameters had occurred between 1995 and 2001. Patients whom had a complete pre-therapeutic evaluation (39%, 709/1834) and received antiviral treatment (38%, 690/1830) were more likely to have abnormal liver biochemistry, cirrhosis and cryoglobulinaemia (P < 0.001). Injecting drug users and HIV-co-infected patients were less likely to have a complete pre-therapeutic evaluation or receive antiviral treatment (P < 0.001). A complete pre-therapeutic evaluation was more often performed in 2001 than in 1995 (39% vs. 6%, P < 0.001), including qualitative HCV RNA testing (91% vs. 68%, P < 0.001), genotyping (59% vs. 7%, P < 0.001) and a liver biopsy (60% vs. 29%, P < 0.001). The frequency of anti-HCV treatment approximately doubled between 1995 and 2001 (20% vs. 38%, P < 0001). Although adherence to consensus recommendations regarding pre-therapeutic evaluation is not ideal, a substantial improvement has occurred since 1995. Nevertheless, means of increasing the availability of antiviral therapies, particularly for patients with HIV co-infection or injecting drug use, require further study.

Adult↗
PubMed2003

Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.

Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.

Adult↗
PubMed2003

Slow viral dynamics of hepatitis C virus genotype 4.

Patients infected with hepatitis C virus genotype 4 (HCV-4) respond to interferon alpha (IFN) as poorly as those infected with genotype 1. However, there is no information on the viral dynamics of HCV-4. Interferon-ribavirin treatment was administered to untreated patients infected with HCV-4. Viral load was assessed with Versant 3.0. Viral dynamics parameters were estimated based on the bi-phasic model for HCV during IFN treatment. Viral kinetics of HCV-4 follow a bi-phasic decline pattern also. The mean effectiveness of IFN in blocking production of HCV-4 was a decline of 77.8% during the first day of treatment. The half-life of free virions was estimated at 3.5 h and that of infected cells from 1.9 to over 70 days. The viral dynamics parameters of HCV-4 appear similar to those of HCV-1 and slower than those of HCV-2. HCV-4 infected patients should be grouped with those with HCV-1 when therapeutic schemes are considered in relation to genotype.

Antiviral Agents↗
PubMed2002

Serological response to infection with different isolates of hepatitis C virus.

Different isolates of hepatitis C virus (HCV) show nucleotide sequence variability throughout the genome. Detection of antibodies to recombinant proteins derived from hepatitis C virus genotype 1, the prototype HCV clone HCV-PT, constitutes the main method for screening HCV infection. The influence of the genomic variability on the serological diagnosis of HCV by enzyme immunoassay remains poorly defined. The aim of this study was to assess the serological reactivity of a panel of well characterized French HCV isolates typed by sequence analysis from patients with chronic hepatitis. The 73 sera samples were tested in three third generation EIA tests and three confirmatory assays. HCV isolates were determined by RT-PCR and sequencing in NS5B region of the genome. The 73 sera were positive in the three EIA tests. The three confirmatory tests showed a weaker reactivity with NS5 protein whatever the genotype, and a lower reactivity in NS4 antigens of non-type 1 sequences, particularly for genotype 3. Even though the reactivity of the antigens differed among the HCV isolates, the 73 isolates from genotype 1-6 were reactive with the three commercial screening assays. These results demonstrate that using a single test is adequate in the routine diagnosis of HCV infection in clinical laboratory, as recommended by the last French and European consensus conference.

Female↗
PubMed2002

Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. RESULTS: ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.

Adult↗
PubMed2001

Changes in histological lesions and serum fibrogenesis markers in chronic hepatitis C patients non-responders to interferon alpha.

BACKGROUND/AIMS: The aim of this study was to evaluate the changes in histological lesions and serum N-terminal peptide of type III procollagen (PIIINP) and hyaluronate (HA) levels in virologic non-responder patients treated by Interferon alpha (IFNalpha). METHODS: We enrolled 183 patients treated by IFNalpha and 56 controls, all with paired biopsy specimens. Yearly liver fibrosis progression was estimated before and during a follow-up of 1 year. RESULTS: By contrast to sustained responders, non-responders (n = 105) did not achieve improvement of histological scores after therapy. Their yearly fibrosis progression rate was similar before and during follow-up (0.18, 95%CI: 0.16-0.20, vs 0.26 (95%CI: 0.12-0.40) fibrosis units/year, NS), and was not different in controls (0.17, 95%CI: 0.06-0.27). The levels of PIIINP and hyaluronate (HA) remained unchanged during follow-up. Histological improvement was observed for the second biopsy in 25% of non-responders, but also in 23% of controls. This improvement was not correlated with decrease of ALT level, viral load, PIIINP, or HA. CONCLUSIONS: Our results suggest that IFNalpha therapy is unable to decrease PIIINP or HA levels and cannot improve the histological outcome in virologic non-responder patients. The histological improvement observed in a subset of patients may be linked to sample fluctuation or lack of reproducibility of histological scores.

Adult↗
PubMed2001

Hepatitis C virus genotyping based on 5' noncoding sequence analysis (Trugene).

Hepatitis C virus (HCV) genotyping of samples from 184 patients with chronic HCV infection by the Trugene 5'NC genotyping kit, based on sequence analysis of the 5' noncoding region (5' NCR), and the InnoLiPA assay was evaluated. In addition to these methods, the 184 samples were also analyzed by sequencing of part of the NS5B of the HCV genome after in-house PCR amplification, as a means of validating results obtained with the 5' NCR. The distribution of the genotypes typed by NS5B sequence analysis was as follows: 1a, 41 samples; 1b, 58 samples; 1d, 1 sample; 2a, 5 samples; 2b, 2 samples; 2c, 7 samples; 3a, 46 samples; 4a, 7 samples; 4c, 1 samples; 4e, 9 samples; 5a, 6 samples; 6a, 1 sample. The Trugene and InnoLiPA assays gave concordant results within HCV types in 100% of cases. The ability to discriminate at the subtype level was 76 and 74% for the Trugene and the InnoLiPA assays, respectively.

5' Untranslated Regions↗
PubMed2000

Hepatitis C virus infection and lymphoproliferative diseases in France: a national study. The GERMIVIC Group.

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenström's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.

Adult↗
PubMed2000

Integrity of the NS5A (amino acid 2209 to 2248) region in hepatitis C virus 1b patients non-responsive to interferon therapy.

BACKGROUND/AIMS: In hepatitis C virus-1b, it has been suggested that an amino acid stretch (aa 2209-2248) of the carboxy terminal half of the non-structural 5A (NS5A) region participates in the response to interferon treatment. We tested the hypothesis that absence of mutations in the NS5A (aa 2209-2248) sequence is required for interferon resistance. We also investigated the importance of different HCV-1b isolates in interferon response in France. METHODS: We determined the NS5A sequences of 70 patients with chronic hepatitis C before IFN therapy and then compared them with HCV-J prototype sequence. The isolates were determined by NS5B sequencing, the "gold standard" method for genotyping and subtyping. Pre-therapeutic viral load was also measured. RESULTS: No sustained virological response was observed in the patients without amino acid substitutions in the NS5A (aa 2209-2248) sequence, and in the patients with HCV-J isolates. Viral load was significantly higher in the patients with no amino acid substitutions in the NS5A (aa 2209-2248) sequence. CONCLUSIONS: In HCV-lb infected patients, an HCV-J strain with no amino acid substitution in the NS5A (aa 2209 2248) region indicates a poor prognosis for response to IFN therapy. The low interferon response rate in HCV-lb infection in Europe is probably not due to a difference between isolates.

Alanine Transaminase↗
PubMed2000

Effects of 1-year interferon-alpha 2a treatment in patients with chronic hepatitis C and persistently normal transaminase activity.

BACKGROUND: Certain chronic hepatitis C carriers have persistently normal transaminase activity. The aims of this study were to determine the virologic and histologic effects of 1 year of interferon-alpha treatment in such patients. METHODS: Thirty-one patients were followed up in our Liver Unit. Eleven accepted interferon-alpha therapy; the 20 others were not treated and served as controls. Interferon-alpha, 3 MU, was given thrice weekly for 1 year. Serum was examined for hepatitis C virus (HCV)-RNA before, at the end of, and 6 months after treatment. Liver biopsy was performed 6 months after the cessation of treatment in 10 of 11 treated patients (one refused biopsy) and after a mean of 30.6+/-22.7 months in the 20 untreated patients. RESULTS: At the end of follow-up two of the treated patients had undetectable serum HCV-RNA and five had increased alanine aminotransferase (ALAT) values. In contrast, only one of the untreated patients had abnormal ALAT activity. All 20 untreated patients were constantly viremic. No significant histologic improvement was observed in the treated patients evaluated by means of post-treatment liver biopsy. The mean annual progression rate of fibrosis was very slow and similar in the treated and untreated patients (0.09 (range, 0-0.62) versus 0.07 (range, 0-0.60) fibrosis units). CONCLUSIONS: One year of interferon-alpha treatment can suppress HCV-RNA in patients with chronic hepatitis C and persistently normal ALAT values followed up over long periods. The rate of fibrosis progression in such patients is very slow, and therapeutic strategies should take this fact into account. Antiviral treatment is debated for patients without fibrosis in initial biopsy specimens.

Adult↗
PubMed2000

[Epidemiological information obtained from anti-hepatitis C virus screening in blood donors and candidates for autologous transfusion from 1992 to 1996 in the Alpes-Maritimes region].

OBJECTIVES: To determine the evolution of the frequency of anti-hepatitis C virus antibodies from 1992 to 1996 in blood donors and in candidates for autologous transfusion in the Alpes-Maritimes region and to assess risk factors. METHODS: Anti-hepatitis C virus antibodies were assessed by second generation ELISA in 1992 and in the first quarter of 1993, and then by third generation ELISA; in all cases, anti-hepatitis C virus antibodies were confirmed by RIBA test. RESULTS: Since 1992 (when the second generation ELISA test became available), the prevalence of anti-hepatitis C virus antibodies in blood donors in the Alpes-Maritimes region (0.54% in 1992 to 0.20% in 1996) has decreased. Positive ELISA anti-hepatitis C virus was confirmed by RIBA in 53 to 68% of anti-hepatitis C virus blood donations. The percentage of anti-hepatitis C virus donors with ALT above the upper limit (donation exclusion threshold) was between 28 and 56%.The most frequent age interval for new anti-hepatitis C virus positive donors was between 30 and 40 years. Since 1992, a third of the anti-hepatitis C virus blood donors agreed to participate in a medical history questionnaire. One or several risk factors were found in almost all donors. The most frequent source of infection was nosocomial (50%). During the 5 years of the study, the number of candidates for autologous transfusion increased: 717 in 1992 to 1 528 in 1996. The prevalence of anti-hepatitis C virus in this older population (mean age: 64 years) decreased progressively (2.9% in 1992 to 1.1% in 1996, P<0, 01) since the prevalence of anti-HBc remained stable, near 12%. Among the 96 subjects found to be anti-hepatitis C virus positive before an autologous transfusion, 49 were transfused before 1990 and 40 had a history of surgery. CONCLUSION: The prevalence of anti-hepatitis C virus has decreased since 1992 in blood donors and in candidates for autologous transfusion which may suggest that there is better screening in the general population and presenting the spread of hepatitis C virus infection.

Adult↗
PubMed1999

[Risk of transmission of hepatitis C through endoscopy of the digestive tract].

NOSOCOMIAL TRANSMISSION: Increasingly implicated in HCV infection in patients with no patent risk factors, nosocomial transmission has been demonstrated between patients hospitalized in the same ward and from health carers to patients. The risk of HCV transmission by medical instruments could only be quantified with a prospective study of examined patients. There is a theoretical risk for all endoscopic examinations whatever organ explored. Instrumental manipulations have been found as the only risk factor in blood donors. VALUE OF FORMER DISINFECTION GUIDELINES: Disinfection protocols for endoscopes have been found to eliminate 3 viruses (HCV, HBV, HIV). The endoscope-related risk could be due to minimal bleeding provoked by biopsies (risk factors independent of HCV infection) via the operator channel. THREE REPORTED CASES OF HVC INFECTION: One case of HVC infection following retrograde cholangiography and two after coloscopy have been reported. In all three cases disinfection was found to be insufficient. Recently, an official statement by the French health authorities indicates that a 20-min gluteraldehyde bath is necessary for optimal efficacy. Instruments susceptible to cause bleeding must be sterilized. The sterilization process must be tracable. The anesthesia-related risk appears to be due to use of multidose bottles or reuse of syringes. SAFE ENDOSCOPY: Disinfection procedures must be rigorously applied. One new perspective is the culture of titratable virus models. Several arguments show that well-conducted disinfection of endoscopes and medical instruments can eliminate all risk of viral transmission, including HCV.

Cross Infection↗
PubMed1999

Prevalence of GBV C/HGV RNA and GBV C/HGV antibodies in French volunteer blood donors: results of a collaborative study.

BACKGROUND AND OBJECTIVES: Posttransfusion hepatitis still occurs at an incidence of about 1 in 118,000 for HBV and 1 in 220,000 for HCV. This collaborative study aimed to determine the prevalence of a novel flavivirus, GBV-C/HGV, even though its role in transfusion-associated hepatitis is uncertain. MATERIALS AND METHODS: GBV-C/HGV RNA was detected by PCR using either the Boehringer detection kit or by primers previously described. HGV antibodies were detected by a serological assay from Boehringer. RESULTS: The observed GBV-C/HGV RNA frequency was 3.4%. HGV antibodies occurred in 9.5% of donors. CONCLUSION: In our study, 12. 9% of the donors had been in contact with the GBV-C/HGV virus.

Adolescent↗
PubMed1998

[Pretreatment with prednisolone enhances the effect of human lymphoblastoid interferon in chronic hepatitis B].

Patients (n = 213) with chronic hepatitis B were randomised to prednisolone (two weeks of 0.6 mg/kg/day, one week of 0.45 mg/kg/day and one week of 0.25 mg/kg/day) or placebo followed by two weeks rest, and were then given human lymphoblastoid interferon 10 MU daily for five days followed by 10 MU thrice weekly for 11 weeks. There were statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). HBeAg disappearance and HBeAg to anti-HBe seroconversion rates were 28 vs. 44% and 23 vs. 38% (placebo vs. prednisolone). Fifteen patients (7.5%) lost HBsAg. Three out of 22 cirrhotic patients (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome. Prednisolone pre-treatment, enhances the effect of lymphoblastoid interferon in chronic hepatitis B. Interferon treatment (with and without prednisolone) should be used with caution in patients with cirrhosis and avoided in patients with evidence of hepatic decompensation.

Adult↗