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Biomedical subjects

D Ouzan

Publications and source records attributed to D Ouzan.

At least 37 records · Page 2Linked to original sources

Comparison of high initial and fixed-dose regimens of interferon-alpha2a in chronic hepatitis C: a randomized controlled trial. French Multicenter Interferon Study Group.

The efficacy of a high-dose de-escalating treatment regimen versus the standard, fixed-treatment regimen of interferon-alpha2a (IFN; Roferon-A) in chronic hepatitis C was evaluated in 291 patients who had elevated alanine aminotransferase (ALT) levels, for at least 6 months prior to the study, and histologically proven chronic hepatitis. Patients were randomized into two groups: 142 patients received IFN at a fixed dose (3 million international units (MIU) three times a week for 6 months) and 149 patients received 6 MIU three times a week for 3 months followed by 3 MIU three times a week for the next 3 months. The groups did not differ significantly with respect to age, gender or percentage of patients with cirrhosis. Response was evaluated by monitoring ALT levels monthly during treatment and during the 6 months post-treatment follow-up. Sixty-one per cent and 66% of the patients in the fixed and de-escalating treatment groups had a primary response (serum ALT normalization) during the treatment period; sustained-response rates at the end of follow-up were 20% and 29%, respectively (not significant). In non-cirrhotic patients, a primary response was recorded in 65% and 70% of the patients in the fixed and de-escalating groups; sustained-response rates were 22% and 33%, respectively. Overall, 62% of patients with a sustained response showed histological improvement. In univariate analysis, patients with sustained response tended to be non-cirrhotic and had lower initial serum gamma-glutamyl transpeptidase and ferritin levels. Multivariate analysis indicated that only ALT activity assessed at month 1 (P < 0.01) was a significant predictor of sustained response. These findings suggest that although the difference in the response rates between the de-escalating (6 MIU three times a week for 3 months; 3 MIU three times a week for 3 months) and fixed (3 MIU three times a week for 6 months) treatment regimens did not reach statistical significance, there was a clear trend towards higher response with the 6 MIU induction dose in patients without cirrhosis.

Adolescent↗

Prospective virological follow-up of hepatitis C infection in a haemodialysis unit.

Hepatitis C virus (HCV) is of major concern in the management of patients on maintenance haemodialysis. Many studies have reported a high prevalence of HCV infection in dialysis centres. The objective of our study was first, to perform a prospective follow-up of the evolution of HCV infection in a haemodialysis centre, and second, to assess the rate of viral clearance in patients on dialysis. For this, genotypes, HCV antibodies (anti-HCV) and HCV RNA were evaluated initially and 9 months later. HCV RNA quantification was also performed. Of 136 patients, 62 (45.6%) were anti-HCV positive by third-generation enzyme immunoassay (EIA 3) in the first survey and 64 of 136 (47.1%) were anti-HCV positive by EIA 3 in the second survey. The rate of new HCV infection, estimated from the two seroconversions between the surveys, was 1.9% per year. One of the two patients was initially HCV RNA positive, with a titre of 0.6 x 10(6) eq ml-1. The viral load measured in the dialysis patients was low and does not seem to be influenced by dialysis. No significant difference was observed in viral load between the two periods nor were there any gender-related differences in viral load. In conclusion, detection of antibodies to HCV, together with HCV RNA, seems to be relevant in haemodialysis patients, but this strategy is not suitable for use in all haemodialysis centres because of its high cost.

Adolescent↗

Lack of influence of hepatitis G virus infection on alcohol-related hepatic lesions.

BACKGROUND: The purposes of this study were to analyse the prevalence and histologic impact of hepatitis G virus (HGV), a newly discovered virus, in alcoholic patients, a population known to be at risk for viral hepatitis. METHODS: One hundred and thirty-nine consecutive alcoholics admitted to our liver unit (106 men and 33 women; mean age, 47.1 +/- 10.9 years) were included in the study. All patients had consumed more than 60 g of ethanol per day for at least 1 year. One hundred healthy blood donors constituted a control group. Antibodies to HGV E2 protein and HGV-RNA testing by reverse transcription-polymerase chain reaction (RT-PCR) with primers derived from the NS5 coding region were performed in all serum samples. RESULTS: A significantly higher seroprevalence of anti-E2 antibodies was observed in alcoholic patients than in healthy blood donors (41 (29.5%) versus 8 (8%); P < 0.0001). Moreover, the prevalence of HGV-RNA was significantly higher in alcoholic patients (13 (9.3%) versus 1 (1%); P = 0.01). HGV-RNA and anti-HGV antibodies were never detected simultaneously. HGV viraemia was not associated with an increased risk of cirrhosis or hepatocarcinoma in alcoholic subjects. CONCLUSIONS: Our study reports a high prevalence of HGV in alcoholic patients. HGV infection does not modify or aggravate the course of alcoholic liver disease.

Case-Control Studies↗

[Primary neuroendocrine tumor in the intrahepatic bile ducts: a rare finding in an asymptomatic patient].

Neuroendocrine tumors of the biliary tree are rare. In all cases except one, diagnosis was made in symptomatic patients. We report a case of an asymptomatic intrahepatic bile duct neuroendocrine tumor in a 74-year old man. To our knowledge, this is the second reported case of an asymptomatic intrahepatic bile duct neuroendocrine tumor. Diagnosis was only made by anatomopathological examination of the tumor after resection. Systemic and immunohistochemical hormonal screening was negative. Twenty months after surgery, the patient was asymptomatic and there was no recurrence.

Aged↗

Serotyping and genotyping of hepatitis C virus (HCV) strains in chronic HCV infection. Commission Hepatologie du CREGG. Club de Reflexion des Cabinets de Groupes en GastroEnterologie.

Hepatitis C virus (HCV) genotypes can be established by methods based on PCR typing and serological typing. The accuracy of these methods depends on their sensitivity and specificity. These should be compared with the reference method, direct sequencing, and analysis of viral genomes. Among the serologic methods recently developed, the performance of a new serotyping assay (RIBA HCV 3.0 SIA, Chiron corporation, Emeryville) was assessed using a panel of 147 well-characterized French isolates from chronic hepatitis C patients. Definitive genotypes of the isolates were established by direct sequencing in 5' NC and in some cases in NS-5B. HCV serotypes 1, 2, and 3 were determined by measuring type specific antibodies to core and NS-4 derived peptide antigens. Of the 147 sera, serotypic-specific antibodies were detected in 136 (sensitivity, 92.5%). The specificity of the RIBA SIA HCV serotyping assay was 92.6% (including samples with mixed results); without these, the specificity was 80.1%. Analysis of the 28 discrepant samples showed that (1) a different serotype was found in 18 samples including five for genotype 1, three for genotype 2, two for genotype 3, five for genotype 4, and three for genotype 5, and that (2) ten patients showed a reactivity with mixed serotypes, one had circulating antibodies to type 1 or 2, and nine had circulating antibodies to type 1 or 3. In summary, except for genotypes 4 and 5, the results of the test were well correlated (85.7%) with those of direct sequence genotyping. The former test is rapid and does not require the strict HCV RNA storage and preservation conditions of the latter. This new method may thus be considered as an alternative for HCV typing. However, although it is convenient, its lower sensitivity compared to the molecular typing method and the discrepant results limit its routine use in a clinical context.

Antibodies, Viral↗

[Clinical significance of detection and quantification of hepatitis C virus RNA in hemodialysis: proposal for a rational diagnostic strategy].

Viral infections due to hepatitis C virus in hemodialysis patients are frequent and have a potential risk of progression towards chronicity. Biochemical and viral markers of infection, are transaminases level, anti-HCV serology and the detection of HCV RNA, respectively. A rational strategy based on routine use of these three diagnostic tools is proposed in order to avoid unnecessary assays and to increase in the case of health cost control, the cost/efficacy ratio. The latter is set up, in the sero-negative hemodialysed, on the early detection of infection by the hepatitis C virus in order to consider of a therapeutic which is able to cure patients and to avoid the ineluctable passage towards chronicity; in hemodialysed with positive HCV serology, the detection of HCV RNA allows to establish the infectiosity status of these hemodialysis patients. It is therefore very important to evaluate prospectively this diagnosis approach in hemodialysis patients.

Genotype↗

[Hepatic resection and transplantation for hepatocellular carcinoma in patients with cirrhosis].

OBJECTIVES: Liver resection and liver transplantation are the only curative treatments for hepatocellular carcinoma in patients with cirrhosis. The aim of this retrospective study was to compare survival and tumor recurrence in patients with cirrhosis after hepatic resection or liver transplantation for hepatocellular carcinoma in patients with cirrhosis. METHODS: Between March 1988 and March 1995, 34 patients underwent liver resection and 30 patients with cirrhosis had liver transplantation for hepatocellular carcinoma. The probability of survival and recurrence were studied according to clinical, biological and pathological factors, defined in liver specimens. Comparisons were performed by the actuarial method and log rank test. RESULTS: Five-year survival after resection and transplantation was 13% and 32.6%, respectively, and 5-year recurrence was 92.6% and 40.9%, respectively (P < 0.01). The diameter of nodules was a significant predictive factor of recurrence in resected patients; the number of nodules was a significant predictive factor in transplanted patients. The combination of these two factors could be used to identify two groups: patients with large carcinoma (diameter > 5 cm and/or number of nodules > 3), and patients with small carcinoma (diameter < or = 5 cm and number of nodules < or = 3). The five-year survival rate of large hepatocellular carcinoma was 17.3% after resection and 0% after transplantation. The five-year survival rate of small hepatocellular carcinoma was 0% after resection and 69.3% after transplantation (P < 0.01). The five-year recurrence of large hepatocellular carcinoma was 72.3% after resection and 100% after transplantation. The five-year recurrence of small hepatocellular carcinoma was 82.6% after resection and 11.1% after transplantation (P < 0.01). CONCLUSIONS: Liver transplantation seems to be the best treatment for small hepatocellular carcinoma, mainly because of a lower recurrence rate. On the other hand, both treatments had a high recurrence rate in large hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group.

BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B. METHODS: Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis. RESULTS: Survival analysis disclosed 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). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment. CONCLUSIONS: Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.

Adult↗

[Course of the recurrence of hepatitis C virus infection after liver transplantation].

OBJECTIVES: Hepatitis C virus recurrence is frequent after orthotopic liver transplantation. The aim of this study was to evaluate the clinical, biological, and histological characteristics of recurrence. METHODS: One hundred and ten patients (91 males, mean age 49 years) with liver transplantation were followed up for more than 1 year (mean: 26 months, range: 12-71). Hepatitis C virus serologic 2nd generation tests were performed before and every 3 months after transplantation in all patients. Serum RNA was detected every 6 months after transplantation by polymerase chain reaction. A percutaneous liver biopsy was performed every year in all patients and in case of abnormal biological liver tests. RESULTS: In 44 patients (40%), hepatitis C virus serology was positive before transplantation, and was unchanged after transplantation. In this group histologic chronic hepatitis was observed in 35 patients (79.5%). The mean Knodell score was 8.4 +/- 2.3, associated with an increase in serum aminotransferases (> twice the upper limit of normal) in 26 cases (74.3%) and with serum RNA in 33 cases (94.3%). The Knodell score was not significantly higher 2 years or more after transplantation than before (9.5 +/- 3.9 vs 7.2 +/- 3.5). In 66 patients with negative hepatitis C virus serology before transplantation, no changes were noted after transplantation. In this group, histologic chronic hepatitis was found in 14 cases (21.2%) associated with serum hepatitis C virus RNA in 7 cases. Actuarial survival rates of the two groups were 97.1% and 91.2% at 2 years, and 93.5% and 86.7% at 5 years, respectively. No death clearly related to hepatitis C virus recurrence was observed. CONCLUSION: Hepatitis C virus recurrence after liver transplantation is frequently associated with chronic hepatitis, and a progressive increase in liver lesions. Nevertheless, the 5-year survival rates was not different in these patients compared to patients with negative hepatitis C virus serology before transplantation.

Adult↗

Anti-GOR and anti-thyroid autoantibodies in patients with chronic hepatitis C.

Anti-thyroid autoantibodies have been described in anti-hepatitis C virus (HCV)-positive patients. It has been suggested that the anti-GOR response is closely related to HCV infection and may reflect an HCV-associated autoimmune phenomenon. This study was designed to evaluate the humoral anti-GOR response in anti-HCV-positive patients with anti-thyroid autoantibodies (group 1, 22 patients) and to compare it with the response in anti-HCV-positive patients without anti-thyroid autoantibodies (group 2, 44 patients) and in anti-HCV-negative patients with autoimmune thyroiditis (group 3, 28 patients). The prevalences of anti-GOR in groups 1, 2, and 3 were, respectively, 72.7, 61.3, and 3.5%. Anti-GOR levels were higher in group 1 than in group 2 or group 3 (P = 0.0001). Moreover, comparison of the Anti-GOR levels of groups 1 and 2 also revealed a statistically significant difference (P = 0.008). Detection of more elevated anti-GOR levels in group 1 patients suggests that anti-thyroid autoantibodies in anti-HCV-positive patients may be related to HCV.

Aged↗

[Risk of transmission of hepatitis C virus by digestive endoscopy].

OBJECTIVE: In 30 to 50% of cases, the route of transmission of virus C remains unknown. The aim of this study was to investigate the effectiveness of manual cleaning and disinfection procedures after endoscopic examinations in highly infected patients. METHODS: In 39 patients with chronic hepatitis C and a high level of replication, a gastroscopy with biopsy was performed with a fully submersible endoscope. Cleaning and disinfection were carried out with the following protocol: cleaning with detergent solution (Sekulyse), rinsing, 3 to 5 min immersion into a glutaraldehyde disinfectant solution (Sekucid) and final rinsing. One hundred mL of sterile water was flushed through the biopsy channel immediately after removal of the endoscope (T1), after cleaning (T2), and after final disinfection (T3). These 100 mL were collected in aliquots for viral and bacterial screening. Virus C particles were searched for in the effluent of the biopsy channel using two methods of polymerase chain reaction. RESULTS: Virus C particles were found in 2 of 39 patients in T1 aliquots collected before washing. Routine cleaning with a detergent eliminated all viral particles, as tests were negative at T2 and T3. The usual bacteria (Pseudomonas, Streptococcus, Neisseria...) were detected at T1 and had disappeared after total disinfection at T3. CONCLUSION: Virus C hepatitis could be transmitted during endoscopic examination, but cleaning and disinfection procedures effectively eliminated all viral particles.

Disinfection↗

Prevention of relapse in patients with chronic non-A, non-B/C hepatitis who respond to alpha-interferon. A controlled multicenter trial of low-dose maintenance therapy. Groupe d'Etude Multicentrique de l'Interféron dans les Hépatites.

We tested the efficacy of maintenance treatment with alpha-2a interferon, 1 megaunit thrice weekly for 6 months, in preventing relapse of non-A, non-B/C hepatitis in remission after treatment with alpha interferon given thrice weekly according to the following dose schedule: 3 megaunits for 3 months, 2 megaunits for 2 months and 1 megaunit for 1 month. Fifty-three patients with hepatitis C in remission were randomly allocated to a treatment group (n = 26) or a control group (n = 27). A relapse (aminotransferase activity > 1.5 times the upper limit of normal) occurred in 46% of the controls and 35% of the treated patients (NS). Maintenance treatment had no significant influence on histopathologic changes evaluated by three independent observers: in both groups the overall score for histologic lesions improved between the initiation of interferon therapy and the end of the study. We conclude that relapses in patients with non-A, non-B/C hepatitis in remission after treatment with alpha interferon at tapering doses are not prevented by maintenance therapy with low-dose alpha interferon. Journal of Hepatology.

Alanine Transaminase↗