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Biomedical subjects

C Brechot

Publications and source records attributed to C Brechot.

At least 91 records · Page 5Linked to original sources
PubMed1992

Failure of acyclovir to enhance the antiviral effect of alpha lymphoblastoid interferon on HBe-seroconversion in chronic hepatitis B. A multi-centre randomized controlled trial.

Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and six controls (14%) (difference: 11%, 95% CI-5-28%). A partial response (HBeAg less than 50% of initial level) was found significantly more often for treated patients (n = 13, 30%) than for controls (n = 2, 5%) (difference: 25%, 95% CI 10-40%). During acyclovir-interferon combination therapy the decrease in HBeAg level was similar to that achieved during therapy with interferon alone. We conclude that acyclovir does not enhance the effect of interferon on serum HBeAg levels. Since HBeAg levels continue to decline during interferon treatment and rebound thereafter to pretreatment levels, prolongation of therapy may yield a higher response rate.

Acyclovir↗
PubMed1992

Hepatitis C viremia and anti-HCV antibodies in alcoholics.

We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab) detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2 positive and in none who were RIBA2 negative. Liver biopsies, available for 12 HCV RNA-positive patients, revealed histological features of purely alcohol-related lesions in seven and mixed alcohol-viral lesions in five. These results indicate that HCV replication is maintained in most alcoholics who score positive for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with histological features typical of alcoholic liver disease.

Adult↗
PubMed1992

[Relapse prevention in liver transplant patients treated for liver involvement due to hepatitis B virus].

Controversy surrounds the indication of liver transplantation in patients with hepatitis B virus infection. The major problem is the very high risk of infection of the graft. Some investigators have suggested that the presence of HBsAg is a contraindication to liver transplantation. Between February 1975 and December 1990, 178 HBs positive patients were transplanted at Paul Brousse Hospital in Professor H. Bismuth's Department, 137 for post hepatitis cirrhosis and 41 for fulminant hepatitis. Since April 1984 we have decided long term immunoprophylactic therapy for all patients with HBs infection. But only from August 1987 our supply of purified anti HBs immunoglobulin has been adequate to treat all our patients according to the following protocol: 10.000 IU during the peroperative phase, 10.000 IU immediately after intervention, 10.000 IU every day for the first 6 days, 10.000 IU when the anti HBs levels were under 150 IU/l. One hundred thirty-nine patients were treated by this method. 110 cleared HBs antigen from their sera and their liver were biologically and histologically free of B virus infection. 29 patients showed reappearance of HBs antigen in their sera and nearly all of them developed objective, histologically confirmed, graft lesions. These lesions are those of classical infection: acute hepatitis, active chronic hepatitis and cirrhosis. So 79% of patients were successfully treated with a follow up of 45 months to 6 months. We also studied the prognostic factors under treatment. The study shows: in the case of fulminant hepatitis, 93% success versus 77% in post hepatitis cirrhosis; in the case of Delta superinfection, 94% success versus 66% with pure B infection; in the absence of HBVDNA in the patient's sera before transplantation, 92% success versus 20% in the presence of HBVDNA. For a better understanding of the overall results, the two following parameters have to be considered: some patients relapsed after stopping their treatment, some other patients, despite repositivation of HBs antigen in their sera showed a paradoxal good evolution. These considerations enable us to obtain HBVDNA positive patients: 10% success, HBVDNA negative patients: Fulminant hepatitis: 100% success B Delta post hepatitis cirrhosis: 100% success B post hepatitis cirrhosis: 92% success.

Hepatitis B↗
PubMed1992

Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction.

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.

Base Sequence↗
PubMed1992

Thymic abnormalities in fetuses aborted from human immunodeficiency virus type 1 seropositive women.

Pathological abnormalities of the thymus were found in 3 of 37 fetuses aborted from human immunodeficiency virus (HIV)-infected mothers. These lesions were located predominantly in the thymic cortex, which contains mostly immature lymphocytes. Areas of focal lymphocyte depletion were infiltrated with CD4+ macrophages and were associated with abnormalities of the epithelial stromal network. No evidence of extensive HIV infection in any of the 37 thymuses was detected by either immunofluorescence or in situ hybridization techniques, although rare cells that expressed HIV antigens were found in 3 fetuses. Although less extensive, this thymic fetopathy was similar to that described in postnatal acquired immunodeficiency syndrome thymuses, strongly suggesting that the lesions were related to HIV infection. Thymic fetopathy might represent the initial injury to the lymphoid system in HIV-infected infants in whom early and severe immunosuppression develops.

Abortion, Induced↗
PubMed1991

Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients.

110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation.

Adolescent↗
PubMed1991

Hepatitis B defective virus with rearrangements in the preS gene during chronic HBV infection.

We have found a defective form of HBV2 in a HBsAg- and anti-HBe-positive patient with liver cancer. Viral deletions were identified in the preS coding region using PCR. The presence of deleted HBV forms was observed in serum, PBMC, and liver samples. After sequencing 12 clones were analyzed (subtype adr). In 9 out of 12 clones a 183-bp in-frame deletion was recorded in the preS1 region (2995 to 3177). Three out of 9 clones also yielded rearrangements of the preS2 N-terminal part. Four out of 9 showed numerous point mutations in the preS1 and preS2 sequence. In addition, 3 out of 12 clones, which did not show the 183-bp preS1 deletion were found to have small deletions and insertions in the same part of the preS1 gene. Immunological mapping using monoclonal anti-preS antibodies showed loss of preS epitopes located at the 3'-part of preS1 and the 5'-part of preS2. On the other hand, epitopes mapped to the 5'-part of preS1 and 3' of preS2 were conserved. PBMC were also tested and solely PCR showed the major form of defective HBV with preS1 183-bp deletion. However, viral deletions in the preS gene eliminated the preS2 promotor region and B- and T-cell recognition sites. In contrast to this, the preS1 binding site to hepatocytes was conserved. Therefore, such deletions would potentially lead to an impairment in viral clearance without affecting viral penetration in liver cells, possibly accounting for chronic HBV infection.

Adult↗
PubMed1991

Hepatitis C virus (HCV)-RNA in non-A, non-B chronic hepatitis in France. Nucleotide sequence of a French HCV isolate.

The sera of 36 French patients with post-transfusional and sporadic non-A, non-B (NANB) chronic hepatitis were investigated, with a combination of serological and polymerase chain reaction (PCR) assays, for HBV and HCV infections. Eighty-nine percent of the patients were found positive with serological and/or molecular tests. Among the positive patients, 68% (22/32) were found positive for both anti-HCV and HCV-RNA, 16% (5/32) and 16% (5/32) were found positive only for anti-HCV or HCV-RNA, respectively. HBV-DNA sequences were detected in two patients associated to the HCV viraemia. This study confirms the extremely high prevalence of HCV infection in NANB chronic hepatitis in France. It also shows the possible co-infection by HCV and HBV in NANB hepatitis. We have also determined the nucleotide sequence of the 5' non-coding, E1, E2/NS1 and NS3/NS4 regions of a French isolate using the polymerase chain reaction. Comparison of these nucleotide sequences with those available from American and Japanese isolates showed a significant genetic variability. The genetic variability is higher in the E2/NS1 (13 to 33% and 12 to 30% at the nucleic acid and amino acid level, respectively) than in the E1 (10 to 28% and 7 to 21%) and NS3/NS4 (5 to 21% and 2 to 7%) regions. The sequence of the French isolate is more closely related to that of the American HCV prototype than to the Japanese HCV isolates. This study confirms the extent of HCV genetic variability.

Amino Acid Sequence↗
PubMed1991

Insulin-like growth factor II (IGF-II) mRNA expression during hepatocarcinogenesis in transgenic mice.

Insulin-like growth factor II (IGF-II) mRNA expression is developmentally regulated in liver tissue. We previously observed the reexpression of fetal IGF-II mRNAs in human primary liver cancer and in surrounding cirrhotic tissue. In order to determine the steps of liver cancer progression where the activation of IGF-II fetal mRNAs occurs, we analyzed IGF-II mRNA expression during hepatocarinogenesis in transgenic mice carrying an antithrombin III-SV40 early region hybrid gene. The comparative analysis of mRNAs encoding IGF-II and other differentiation-associated proteins, as well as histological analysis, indicate that the reexpression of fetal IGF-II mRNAs takes place in specific steps of liver cancer progression, both in early pretumorous lesions and in well-differentiated hepatocellular carcinomas.

Aging↗
PubMed1991

Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease.

We conducted a retrospective study in 229 patients to determine the prevalence of hepatitis C virus (HCV) according to the type of liver disease and also the serum hepatitis B virus (HBV) status. There were 55 cases of hepatocellular carcinoma (HCC), 78 cases of alcoholic cirrhosis (AC) and 96 cases of non-cirrhotic alcohol liver disease (NCA). Half the AC and NCA groups were constituted of patients with or without serum HBV markers. The prevalence of anti-HCV antibodies in HCC (58.2%) was significantly higher than in the other groups (AC, 35.9%; NCA, 17.7%). Combining the two AC and NCA groups gave a 25.8% anti-HCV prevalence in the alcoholics. Altogether anti-HCV antibodies were more frequently present in HBV-positive than in HBV-negative patients (42.2 vs. 26.1%, p less than 0.01), although the difference was not significant when the HCC group was separately analysed. The S/N ratio of anti-HCV-positive samples varied according to the type of the disease (tumorous vs. non-tumorous) and to the serum HBV status. Indeed, 65.6% of HCC had a S/N greater than 4 compared to only 32.2 and 23.5% in AC and NCA, respectively (p less than 0.01). On the other hand more than half of the AC and NCA had a S/N less than 2, indicating possible artefacts in certain cases. The 15 HBsAg and anti-HCV-positive patients had a significantly lower mean S/N than patients displaying only antibodies against HBV, even in the HCC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Emergence of and takeover by hepatitis B virus (HBV) with rearrangements in the pre-S/S and pre-C/C genes during chronic HBV infection.

We have shown, by analyzing serial serum samples from a chronic hepatitis B virus (HBV) carrier, the emergence of HBV DNA molecules with nucleotide rearrangements in the pre-S/S and pre-C/C genes. Serum samples were obtained at four different times (1983, 1985, 1988, and 1989) from an HBsAg- and HBeAg-positive carrier with chronic hepatitis. The polymerase chain reaction was used to amplify the pre-S/S and pre-C/C genes. The amplified products were cloned, and 8 to 10 independent clones were sequenced. In 1983 and 1985 only one type of HBV DNA molecule was observed. Nucleotide divergence relative to the adw2 subtype was 4.7, 7.2, and 1.6%, for the pre-S1, pre-S2, and S regions, respectively, and 2.2 and 3.9% for the pre-C and C regions, respectively. In 1988 and 1989, HBV DNA forms with marked rearrangements of both the pre-S/S and pre-C/C regions were evidenced. In the pre-S/S region, they comprised two distinct HBV DNA molecules. The first showed nucleotide divergence of 20.4, 14.8, and 3.3% for the pre-S1, pre-S2, and S regions when compared with the adw2 sequence. In addition, nucleotide deletions in the pre-S1 region led to the appearance of a stop codon. The second was created by recombination between the original and mutated HBV DNA. In the pre-C/C region, the mutated viral DNA showed 11.7% divergence when compared with the adw2 sequence. A point mutation led to the creation of a stop codon in the pre-C region, together with an insertion of 36 nucleic acids in the core gene. Most of this DNA insertion was identical to that reported in an independent HBV isolate but showed no significant homology with known sequences. Semiquantitative estimation of the proportion of wild-type and mutated HBV DNA molecules showed a marked increase in the mutated forms during the period of follow-up. Sucrose gradient analysis indicated that the defective HBV DNA molecules were present in circulating virions. Western immunoblot analysis showed the appearance of modified translation products. Our findings thus indicate the emergence of and gradual takeover by mutated HBV DNA forms during the HBV chronic carrier state. The rearrangements we observed in the pre-S/S and pre-C/C genes might lead to changes in the immunogenicity of the viral particles and thus affect the clearance of the virus by the immune system.

Amino Acid Sequence↗
PubMed1991

An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.

Inhibition of okadaic acid-sensitive phosphatases released the cyclin degradation pathway from its inhibited state in extracts prepared from unfertilized Xenopus eggs arrested at the second meiotic metaphase. It also switched on cyclin protease activity in a permanent fashion in interphase extracts prepared from activated eggs. Even after cdc2 kinase inactivation, microinjection of okadaic acid-treated interphase extracts pushed G2-arrested recipient oocytes into the M phase, suggesting that the phosphatase inhibitor stabilizes the activity of an unidentified factor which shares in common with cdc2 kinase the maturation-promoting factor activity.

Animals↗
PubMed1991

Expression of insulin-like growth factor II, alpha-fetoprotein and hepatitis B virus transcripts in human primary liver cancer.

Insulin-like growth factor II is a fetal growth factor structurally and functionally related to insulin and insulin-like growth factor I. Its mRNA expression is developmentally regulated in human liver, the reexpression of insulin-like growth factor II fetal transcripts being often observed in primary liver cancer. Insulin-like growth factor II and alpha-fetoprotein mRNAs were studied in 16 human primary liver cancers, most of which were highly differentiated. Hepatitis B virus transcripts were also analyzed in the tumors from hepatitis B virus chronic carriers. alpha-Fetoprotein mRNA was detected in only four tumors and in one nontumorous cirrhotic tissue; all these samples also displayed insulin-like growth factor II fetal transcripts. Furthermore, fetal insulin-like growth factor II mRNAs were observed in five tumors and six nontumorous cirrhotic areas not expressing alpha-fetoprotein mRNA. The presence of hepatitis B virus RNA was only observed in tissues not expressing alpha-fetoprotein or fetal insulin-like growth factor II mRNA. In conclusion, fetal insulin-like growth factor II transcripts are more frequently observed than alpha-fetoprotein mRNA in highly differentiated liver cancers and in surrounding cirrhotic areas. The reexpression of fetal insulin-like growth factor II transcripts might then be a marker of early steps of liver cell transformation.

Carrier State↗
PubMed1991

Significance of anti-HBx antibodies in hepatitis B virus infection.

Serological responses to hepatitis B virus-X determinants have been noted in human sera, but conflicting findings concerning the correlation of anti-HBx antibodies with different stages of hepatitis B virus infection or pathological sequelae have been reported. Using an adenovirus-based eukaryotic vector, the 17 kD X protein was efficiently expressed in 293 cells. Cellular extracts containing the eukaryotic X protein have been used to screen for anti-HBx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis B virus chronic hepatitis, hepatocellular carcinoma and acute viral hepatitis. Sera from 32 of 171 (19%) chronic hepatitis B virus patients were positive for anti-HBx antibodies. Only one of thirty-two (3%) HBsAg-negative, anti-HBs/anti-HBc-positive chronic hepatitis serum was anti-HBx positive. Very few sera from primary hepatocellular carcinoma patients showed positivity for anti-HBx (8 of 149 or 5%). Anti-HBx were also detected in 8 of 48 (17%) acute viral hepatitis patients. In the four cases that were followed up weekly, anti-HBx antibodies appeared 3 to 4 wk after the onset of the clinical signs. To compare the X protein expressed in eukaryotic and prokaryotic cells as a substrate for anti-HBx antibody detection, 171 sera were screened with HBx fusion proteins expressed in Escherichia coli. The prokaryotic cell extract test seems to be more sensitive. During the chronic phase of hepatitis B virus infection, the presence of anti-HBx antibodies detected with the eukaryotic cell extract correlates with the presence of well-established markers of ongoing viral replication: serum hepatitis B virus-DNA (p less than 0.001) and intrahepatic HBcAg expression (p less than 0.001).

Biomarkers↗