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Biomedical subjects

P Marcellin

Publications and source records attributed to P Marcellin.

At least 127 records · Page 7Linked to original sources

Comparison of the sensitivity of nested PCR in the 5' non-coding and the NS5 regions of the HCV genome.

Thirty-seven patients with antibodies to hepatitis C virus detected by second-generation enzyme-linked immunoabsorbent assay were studied. Serum of 20 patients with increased serum alanine aminotransferase and 17 patients with normal serum alanine aminotransferase levels was tested for hepatitis C virus RNA with reverse transcription and nested polymerase chain reaction. The nested polymerase chain reaction was independently performed in both the 5' non-coding region and putative non-structural 5 region. The results of these 37 sera were: 28 5' non-coding region polymerase chain reaction positive (17 with increased alanine aminotransferase) and 13 non-structural 5 region polymerase chain reaction positive (8 with increased alanine aminotransferase). Eighteen of the 20 patient with increased alanine aminotransferase (90%) and 11 of the 17 patients with normal alanine aminotransferase (65%) were polymerase chain reaction positive. Of the 28 5' non-coding region polymerase chain reaction positive subjects, 16 were non-structural 5 region polymerase chain reaction negative. The failure to amplify hepatitis C virus-RNA using the non-structural 5 region primers in these patients may be related to the higher genetic variability in the non-structural 5 region than in the 5' non-coding region. Overall, the 5' non-coding region polymerase chain reaction provides a more reliable test for the diagnosis of hepatitis C virus. However, a recombinant immunoblot assay-2 indeterminate patient with increased alanine aminotransferase was polymerase chain reaction negative in the 5' non-coding region and polymerase chain reaction positive in the non-structural 5 region. For this patient, the specificity of the non-structural 5 amplified product was confirmed by hybridization and sequencing.

Base Sequence↗

Comparison of anti-HBe-positive and HBe-antigen-positive chronic hepatitis B in France. French Multicentre Group.

Two groups of patients with HBV DNA-positive chronic active hepatitis B, from 20 French hospitals, separated according to HBe status, were prospectively subjected to a comparative analysis of various epidemiological, clinical, biochemical, serologic and histologic features. There were 61 patients with anti-HBe and 215 patients with HBeAg. At diagnosis, 25 variables were compared between the two groups. Some of the patients were followed up for 1 year. Anti-HBe chronic hepatitis B occurred with a prevalence of 22.1%. In the anti-HBe-chronic hepatitis B group, the patients were older, and more often of Southern European origin; the source of infection was more frequently unknown, hepatitis B markers were more frequently observed within the family, and the estimated duration of liver disease was longer. Serum HBV DNA levels were lower in the anti-HBe-positive group. No difference was observed in ALT levels at diagnosis and during follow up in the patients studied. Cirrhosis was more frequent in the anti-HBe-positive group. There was no difference in histological activity score between the two groups. These results suggest that anti-HBe-positive, chronic active hepatitis B is not rare in France, and that the higher occurrence of cirrhosis in this group may be related to a longer duration of the disease.

Adult↗

Detection and quantitation of serum HCV-RNA by branched DNA amplification in anti-HCV positive blood donors.

The detection of serum HCV-RNA needs to be standardized. The aim of this study was to assess the effectiveness of the branched DNA amplification method in detecting and quantitating serum HCV-RNA in 54 blood donors, 33 with and 21 without increased serum alanine aminotransferase levels and with detectable serum HCV-RNA by polymerase chain reaction. HCV-RNA was detected by branched DNA signal amplification in 42/54 (77%) of the blood donors. Positivity rates were not different among the 21 blood donors with normal and the 33 blood donors with increased serum alanine aminotransferase levels (86% and 76%, respectively). Median serum HCV-RNA levels were not different among donors with or without increased serum alanine aminotransferase levels (28.6 x 10(5) Eq/ml and 14.7 x 10(5) Eq/ml, respectively). There was no significant correlation between serum alanine aminotransferase levels and serum HCV-RNA levels. These findings show that branched DNA signal amplification identifies most of the donors with true hepatitis C virus viremia and that the level of hepatitis C virus replication is not correlated to serum alanine aminotransferase levels.

Adult↗

Etiology of chronic hepatitis in France: predominant role of hepatitis C virus.

The aim of this study was to assess the causes of histologically proven chronic hepatitis in a series of 357 consecutively admitted patients. Patients with chronic alcohol intake above 50 g per day, Wilson's disease, idiopathic hemochromatosis or homozygous alpha-1 antitrypsin deficiency were excluded. Sera of all patients were tested for antibodies to hepatitis C virus with second-generation enzyme-linked immunoassay and recombinant immunoblot assay, for markers of hepatitis B and hepatitis D viruses, and for autoantibodies. Detection of hepatitis C viral RNA by polymerase chain reaction was attempted if recombinant immunoblot assay was indeterminate, or if both viral and autoimmune markers were absent. If no serum markers, including HCV RNA, were found, the cause of chronic hepatitis was considered as unknown. The cause of chronic hepatitis was found in 343 cases (96.4%), including three patients with HCV RNA as the only marker. Chronic hepatitis was related to hepatitis C virus in 51.8%, to hepatitis B virus in 32.8% (including hepatitis D infection in 3.1%), and to autoimmune hepatitis in 5.9% of cases, respectively. No case of drug-induced chronic hepatitis was observed in this series, and in 5.9% of cases, there were probably multiple causes. Finally, in 3.6% of the cases the cause of chronic hepatitis remained unknown despite extensive evaluation suggesting the existence of a non-A, non-B, non-C viral agent.

Adult↗

Indeterminate third-generation recombinant immunoblot assay in hepatitis C virus infection. Group d'Etudes Moléculaires des Hépatites (GEMHEP).

Third-generation recombinant immunoblot assay is widely used for the validation of the serological diagnosis of hepatitis C virus infection. To determine whether indeterminate recombinant immunoblot assay 3.0 patterns may be associated with viral replication and liver disease, 89 indeterminate patterns were studied (67 c22n 14 c33c, 5 c100p and 3 NS5); 35 (39%) had immunosuppression. Serum alanine aminotransferase activity was increased in 49 (55%); HCV RNA was evidenced through polymerase chain reaction in 52 (58%). The observation of indeterminate recombinant immunoblot assay 3.0 justifies investigation of liver disease and search for HCV RNA, since a large proportion of individuals with such patterns are hepatitis C virus-infected.

Adolescent↗

Hepatitis C virus (HCV) viremia in human immunodeficiency virus-seronegative and -seropositive patients with indeterminate HCV recombinant immunoblot assay.

Positivity of recombinant immunoblot assay (RIBA) for detection of antibodies to hepatitis C virus (anti-HCV) is usually associated with HCV viremia. The significance of an indeterminate RIBA result, defined by reactivity to only one HCV antigen, is unclear. Whether anti-human immunodeficiency virus (HIV)-negative or -positive subjects with an indeterminate RIBA have HCV viremia detectable by polymerase chain reaction was investigated. An indeterminate RIBA was found in 48 (15%) of 318 anti-HIV-negative and 38 (23%) of 167 anti-HIV-positive subjects (P < .05). Clinical stage was IV-C-1 or IV-C-2 in 82% of those anti-HIV-positive. HCV viremia was found more frequently in anti-HIV-positive (89%) than in anti-HIV-negative subjects (50%) with an indeterminate RIBA (P < .05). These results suggest an impaired anti-HCV response associated with HIV infection.

Alanine Transaminase↗

Distribution of hepatitis B virus DNA sequences in different peripheral blood mononuclear cell subsets in HBs antigen-positive and negative patients.

Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV-infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers.

Carrier State↗

Long-term histologic and viral changes in patients with chronic hepatitis C who responded to alpha interferon.

We assessed the long-term outcome in 24 patients with chronic hepatitis C who responded to alpha interferon. All patients were followed up for 12 months, and 16 patients were followed up 41 +/- 9 months. During the follow-up period, 18 of the 24 patients (75%) relapsed (serum ALT levels increased again); 16 had an early relapse within the 6 months and two had a late relapse 21 and 36 months after therapy; one cirrhotic patient with relapse died. Serum HCV RNA remained detectable in the two patients before the late relapse and in three of the six patients with sustained biochemical response. Histologic assessment 13 to 31 months after therapy showed a decrease in activity in most patients, even in some of those with relapse, but the decrease in portal inflammation was more marked (p < 0.05) in patients with sustained biochemical response. Liver HCV RNA was not detectable in the two sustained responders who were negative for serum HCV RNA. Despite biochemical remission induced by interferon therapy, HCV replication persists in many patients with a potential risk of late relapse. In contrast, some patients have no long-term detectable HCV RNA, suggesting clearance of HCV. Long-term histologic improvement of portal inflammation in most patients confirms the beneficial effect of interferon.

Adult↗

Pretransplantation interferon treatment and recurrence of hepatitis B virus infection after liver transplantation for hepatitis B-related end-stage liver disease.

Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis is commonly complicated by reinfection with the hepatitis B virus, with rapidly progressive liver disease and poor survival rate. We assessed the efficacy of prior therapy with recombinant interferon-alpha on the prevention of posttransplantation hepatitis B virus reinfection. Twenty-two patients with hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha until transplantation. The rates of posttransplantation hepatitis B virus reinfection and survival in this group were compared with those in a group of 26 patients previously given transplants for the same disease but not given interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis was applied after transplantation in both groups. Recombinant interferon-alpha was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with disappearance of serum hepatitis B virus DNA in seven of the eight patients initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of the three patients initially positive for HBeAg. Serum hepatitis B virus DNA remained detectable with polymerase chain reaction at transplantation in 56% of the interferon-treated patients. After transplantation, hepatitis B virus reinfection was more frequent in polymerase chain reaction-positive than in polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One patient's condition deteriorated during interferon treatment; this patient was not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared from serum) improved so markedly during treatment that they were not given transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prevalence of hepatitis C virus infection in asymptomatic anti-HIV1 negative pregnant women and their children.

The prevalence of hepatitis C virus (HCV) infection was studied prospectively in pregnant women in France and their children by detection of anti-HCV with second-generation ELISA (ELISA2). In ELISA2-positive women, anti-HCV was detected with second- and third-generation RIBA (RIBA2 and RIBA3) and serum HCV RNA was detected with PCR. Among 670 women, anti-HIV1-negative, 26 (3.9%) were positive with ELISA2. RIBA2 was positive in 13 and HCV RNA was found in 10. Ten ELISA2-positive women had a further evaluation with assessment of HCV infection in their children. Among the 10 children born to the index pregnancy, only one was positive with ELISA2 and RIBA2 but negative with RIBA3 and PCR; the nine other children were ELISA2, RIBA2, RIBA3, and PCR negative. All 26 siblings (2-16 years old), of whom 14 were born to PCR-positive mothers, were ELISA2 and RIBA2 negative. We conclude that among anti-HIV1-negative pregnant women with normal serum ALT levels, the prevalence of HCV infection is relatively high but the risk for mother-to-infant transmission of HCV seems to be low.

Adult↗

Cryoglobulinemia with vasculitis associated with hepatitis C virus infection.

Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis. This report presents four cases of cryoglobulinemia with vasculitis associated with chronic hepatitis related to hepatitis C virus infection. Hepatitis C virus infection was ascertained in the four patients by both the presence in the serum of anti-HCV antibodies detected by the four-antigen recombinant immunoblot assay and of HCV RNA detected by polymerase chain reaction. In two patients tested, anti-HCV antibodies were not detected after centrifugation in the purified cryoglobulin but were detected in the supernatant. HCV RNA was detected in the purified cryoglobulin in all four patients and was detected in the supernatant in three patients. In one patient receiving recombinant interferon alfa, serum aminotransferases normalized and cryoglobulin disappeared; in another patient receiving recombinant interferon alfa, serum aminotransferases remained high and the cryoglobulin persisted. The presence of HCV RNA in the cryoglobulin and the parallelism of the changes of the cryoglobulinemia and of the serum aminotransferases during recombinant interferon alfa administration suggest that HCV infection is responsible for the production of cryoglobulinemia and vasculitis. It is proposed that HCV infection is a cause of cryoglobulinemia associated with chronic hepatitis.

Adult↗

Chronic non-B, non-C hepatitis among blood donors assessed with HCV third generation tests and polymerase chain reaction.

Forty five blood donors with increased serum aminotransferases levels had liver histologic assessment and were tested for antibodies to hepatitis C virus (anti-HCV) with second and third generation ELISAs and RIBAs, and for HCV RNA with polymerase chain reaction (PCR) in serum and liver tissue. Twenty-nine of these 45 donors (65%) had steatosis without chronic hepatitis. Sixteen (35%) had chronic hepatitis. Twelve had evidence of HCV infection. Four had no evidence of HCV infection demonstrable by ELISA, RIBA or PCR. These four patients had no known cause of chronic hepatitis and no risk factor for parenterally acquired viral infection was found in them. This observation supports the hypothesis that a non-B, non-C virus might be implicated in chronic hepatitis. However, this hypothesis remains to be demonstrated.

Blood Donors↗

Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C.

OBJECTIVE: Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy. DESIGN: Prospective study. PATIENTS: A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks. MEASUREMENTS: TSH and autoantibodies against thyroid were looked for at (-2) weeks and 24 weeks in all patients. Blood samples obtained at (-2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year. RESULTS: Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P < 0.001) antimicrosomal, antithyroglobulin, and/or anti-TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 1.5 years after interferon withdrawal. No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases. CONCLUSION: (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy; (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.

Adolescent↗

Hepatitis C virus infection in anti-HIV positive and negative French homosexual men with chronic hepatitis: comparison of second- and third-generation anti-HCV testing.

To determine the prevalence of hepatitis C virus (HCV) infection in homosexuals with chronic hepatitis, we tested for anti-HCV antibodies 113 (47 anti-HIV positive) French non-drug-addicted homosexual men admitted for chronic viral hepatitis. Anti-HCV were detected with second- and third-generation ELISAs (ELISA2 and ELISA3) and RIBAs (RIBA2 and RIBA3). Chronic hepatitis was related to non-A, non-B infection in four, to hepatitis D virus (HDV) infection in five and to hepatitis B virus (HBV) infection in 104 patients. Anti-HCV positivity was found in 50.4% and 12.4% of the 113 patients, with ELISA2 and ELISA3, respectively. Positivity with RIBA2 and RIBA3 was found in only six of the 57 ELISA2 positive patients (all six were ELISA3 positive). The high prevalence of positivity with ELISA2 not confirmed by RIBA2 or RIBA3 suggests false-positive results. ELISA2 positive results were more frequent with frozen serum samples than with fresh serum samples (62% vs 23.5%, p = 0.0003). However, even with fresh serum, ELISA2-positive RIBA-negative results remained frequent in anti-HIV positive patients. ELISA3 seems to give more specific results. We conclude that the prevalence of HCV infection, as assessed with RIBA, was 5.3% among French homosexual men with chronic hepatitis (3.8% after exclusion of transfused patients). This low prevalence suggests that homosexual transmission of HCV is relatively uncommon.

Adult↗

Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine.

In this pilot study of the effects of interferon alfa in 10 anti-HIV positive, chronic hepatitis B patients treated with zidovudine (AZT), tolerance to interferon was good and similar to that in anti-HIV negative patients. After treatment, the HIV stage and CD4 lymphocyte count were unchanged. In two patients hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) disappeared and the serum alanine aminotransferase (ALT) returned to normal; loss of hepatitis B surface antigen (HBsAg) with absence of histopathological activity was observed after treatment in one of these patients. These preliminary results need to be confirmed by a larger study.

Adult↗