A proposed system for the nomenclature of hepatitis C viral genotypes.
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Genotype↗
Biomedical subjects
C Brechot
Publications and source records attributed to C Brechot.
Cell lineage study in the liver using retroviral mediated gene transfer. Evidence against the streaming of hepatocytes in normal liver.
The fate of normal hepatocytes in adult rat liver was studied after genetic labeling using the Escherichia coli beta-galactosidase gene coupled to a nuclear localization signal. The marker gene was introduced by direct in vivo retroviral-mediated gene transfer into hepatocytes 24 hours after partial hepatectomy. Analysis of beta-galactosidase expression in the liver at various time after gene transfer revealed that labeled hepatocytes were distributed throughout the entire lobule with a predominance in the periportal and mediolobular regions. Long-term experiments demonstrated that division of hepatocytes did occur as was revealed by the increasing number of beta-galactosidase-positive cells in isolated clusters. There was no evidence for the participation of stem cells in this process. Moreover, we found that after more than 1 year, the pattern of distribution of positive cells within the lobule was not modified. This suggests that hepatocytes do not migrate from the portal space to the perivenous region, as has been previously hypothesized.
Animals↗
Localization of cyclin A at the sites of cellular DNA replication.
Cyclin A is a nuclear protein which is part of a kinase complex with either p34cdc2 or p33cdk2. Cyclin A is required in higher eukaryotic cells at the G1/S and the G2/M transitions. To examine the relationship between cyclin A and DNA replication, we simultaneously labeled exponentially growing HeLa cells for the distribution of cyclin A and proliferating cell nuclear antigen (PCNA). We have now demonstrated, by means of immunoelectron microscopy, that cyclin A is located at the sites of DNA replication visualized by both BrdU and PCNA labeling. Thus cyclin A may play a significant role in the phosphorylation of proteins at or near the sites of DNA replication.
Bromodeoxyuridine↗
HCV infection in alcoholics.
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Alcoholism↗
Post-transfusional anti-HCV-negative non-A non-B hepatitis (II) serological and polymerase chain reaction analysis for hepatitis C and hepatitis B viruses.
Hepatitis C virus (HCV) is a major etilogical agent of post-transfusional and sporadic acute and chronic hepatitis in various geographical areas. However, anti-HCV seroconversion was uncommon in a recent study of patients with post-transfusional hepatitis in Paris, France (N. Asar et al., companion paper). The aim of the present study was to detect viral markers, in particular HCV RNA and hepatitis B virus (HBV) DNA, in these patients. A combination of second-generation assays for anti-HCV antibodies and the polymerase chain reaction were used to identify HCV RNA and HBV DNA sequences in serum samples collected before and after transfusion from patients who developed non-A, non-B hepatitis. Eighteen cases of acute, post-transfusional, non-A, non-B hepatitis were identified in the prospective clinical survey. Only three of these 18 subjects developed anti-HCV antibodies in second-generation tests. HCV RNA was identified in the serum of these three subjects but in none of the others. Two patients who were anti-HCV-negative had polymerase chain reaction evidence of HBV DNA. Known viral markers were not identified in 13 of the 18 patients with acute post-transfusional non-A, non-B hepatitis. These results raise the issue of HCV strains or 'non-A, non-B, non-C' viruses not identified by current HCV and HBV markers and implicated in post-transfusional hepatitis in France.
Base Sequence↗
Presence of HIV-1 in human parenchymal and non-parenchymal liver cells in vivo.
The infection of liver cells by HIV-1 was investigated in vivo. Liver biopsies from 13 anti-HIV-1 antibody-positive patients were studied and HIV-1 DNA was revealed by polymerase chain reaction (PCR) in eight. In situ hybridization demonstrated the presence of HIV-1 RNA in all eight PCR-positive liver specimens. Mononuclear inflammatory cells in the portal tracts and Kupffer cells were labeled by a HIV-1 35S-RNA probe in all cases and by an anti-p24 monoclonal antibody, in seven cases. In addition, hepatocytes also clearly scored positive for HIV-1 RNA in three cases. These results demonstrate the infection of both parenchymal and non-parenchymal liver cells by HIV-1 in vivo and therefore show that HIV-1 can infect an epithelial CD4-negative cell type.
Acquired Immunodeficiency Syndrome↗
Assessment of screening tests for transfusion-associated non-A non-B hepatitis.
Non-A non-B hepatitis is the most common serious sequela of blood transfusion, and its screening has become an essential goal of blood transfusion centers. Before 1989, two surrogate screening tests (for alanine aminotransferase and for antibody to hepatitis B core antigen) were used; in 1989, a direct test for the antibody to hepatitis C virus (the main agent of this hepatitis) was developed. The French National Agency for the Development of Medical Evaluation undertook an investigation to determine the optimal prevention strategy for posttransfusion non-A and non-B hepatitis (PTH). A detailed literature review was performed, complemented by expert group opinion. The performance of each test was derived indirectly by calculating the number of cases of PTH averted by each test. Hepatitis C virus testing is probably the most promising strategy, but different policies can be developed given the uncertainties of scientific data. Cost considerations should be taken into account in identifying the best screening strategy.
Alanine Transaminase↗
Hepatitis C virus RNA in serum of blood donors with or without elevated transaminase levels.
The pattern of hepatitis C virus (HCV) viremia in blood donors who are positive for antibody to HCV (anti-HCV) according to the level of transaminase activity is unclear. A polymerase chain reaction-based HCV RNA detection method was used to study two clearly defined groups of anti-HCV-positive blood donors with repeatedly normal (n = 27) and elevated (n = 17) alanine aminotransferase (ALT) levels. HCV RNA was detected in only 4 of 27 blood donors with normal ALT values and 15 of 17 with elevated ALT values. These results indicate that anti-HCV-positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases. Polymerase chain reaction should be useful in the surveillance of anti-HCV-positive blood donors with normal ALT levels, by identifying those who might benefit from further investigation and treatment.
Alanine Transaminase↗
Characterization of dual HIV-1 and HIV-2 serological profiles by polymerase chain reaction.
OBJECTIVE: To evaluate the frequency of dual HIV-1 and HIV-2 DNA sequences in patients with dual serological profiles. DESIGN: We tested 40 samples from AIDS patients living in Abidjan, Côte d'Ivoire. METHODS: Dual serological reactivity was determined by double Western blot and two enzyme-linked immunosorbent assays with recombinant proteins and synthetic peptides as antigens. The Western blot was considered to show dual reactivity when sera reacted with at least two glycoproteins and one core protein of each virus. HIV DNA sequences were detected by hybridization to radiolabelled probes of polymerase chain reaction (PCR) products amplified using specific primers. RESULTS: Both HIV-1 and HIV-2 DNA sequences were detected in four out of 11 samples with a dual serological profile and in four out of 24 samples with anti-HIV-1 antibodies only. CONCLUSION: These results show that dual HIV-1 and HIV-2 serological profiles are not always due to infection by both viruses, and emphasize the need for a combination of serological and PCR assays for the appraisal of these viral infections.
AIDS Serodiagnosis↗
Lack of mother-to-infant transmission of hepatitis C virus in human immunodeficiency virus-seronegative women: a prospective study with hepatitis C virus RNA testing.
The published risk of mother-to-infant transmission of hepatitis C virus varies according to the population studied and the tests used. In a prospective study we used the polymerase chain reaction to assess the risk of vertical transmission of hepatitis C virus in an unselected population of women uninfected by human immunodeficiency virus. Hepatitis C virus antibodies were sought with a second-generation enzyme-linked immunosorbent assay in 2,367 consecutive pregnant women. Forty-one were positive, and 17 consented to serological follow-up of their offspring (n = 18). A second-generation recombinant immunoblot assay, ALT determination and hepatitis C virus RNA testing were performed on maternal sera obtained during pregnancy and sera from the offspring at birth and thereafter. Five older brothers or sisters were also tested. Hepatitis C virus RNA sequences in serum were amplified with a modified nested polymerase chain reaction procedure with primers from the highly conserved 5' noncoding region of the hepatitis C virus genome. All the neonates were positive for hepatitis C virus antibodies, with enzyme-linked immunosorbent assay titers and recombinant immunoblot assay patterns similar to those of their mothers. After birth hepatitis C virus antibodies gradually disappeared within 6 mo. Hepatitis C virus RNA was consistently negative in the 18 children from birth to 24 mo (range = 3 to 24 mo) and in the 5 older children, regardless of the hepatitis C virus polymerase chain reaction status of the mothers (8 of whom were positive).(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
[Efficacy of immunotherapy with vaccination against hepatitis B virus on virus B multiplication].
In a prospective, non-randomized, pilot study, we evaluated the efficacy of hepatitis B virus (HBV) vaccination in inhibiting HBV replication of chronic hepatitis B. Fourteen consecutive chronic HBs antigen carriers received standard vaccination with three injections of the GenHevac B vaccine, one month apart. All the patients had active HBV replication with chronic hepatitis but not cirrhosis. They were compared to a historical group of 34 patients who fulfilled the same inclusion criteria. Over the 6-month follow-up period after the first injection, serum HBV DNA became undetectable in 3 patients (21.4%). Four additional patients (28.6%) showed a significant decrease in HBV replication. In 4 cases, the disappearance of or decrease in HBV DNA was preceded by an increase in transaminase activities, which was also observed in one patient who did not modify his viral replication. Vaccination was otherwise uneventful. By contrast, during a mean follow-up of 40 months, only 3 (9%) of the 34 unvaccinated patients who served as controls lost serum HBV DNA, giving a 6-month HBV DNA disappearance rate of 1%. In sum, vaccination appeared able to reduce or stop HBV replication in half of the chronic HBsAg carriers with chronic hepatitis. This additional therapeutic tool may enhance the rate of response to interferon-alpha therapy, which is dependent on the level of HBV replication. Thus, immunotherapy should be considered of potential importance for the treatment of HBV infection.
Adult↗
[Bullous drug eruption caused by Introna].
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Adult↗
Allograft biopsies in situ hybridization HBVDNA detection of serum HBs Ag-repositive patients treated with anti-HBV immunoprophylaxis after liver transplantation for HBV cirrhosis.
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Biopsy↗
Patterns of hepatitis delta reinfection after liver transplantation and their evolution during a long term follow-up.
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Adult↗
Interactions between human immunodeficiency virus-1, hepatitis delta virus and hepatitis B virus infections in 260 chronic carriers of hepatitis B virus.
To evaluate the factors determining the severity of chronic hepatitis B virus infection and the interactions of human immunodeficiency virus and hepatitis delta virus infections, we retrospectively analyzed 260 patients, 146 of whom were followed for a mean of 31.4 +/- 1.8 mo. Human immunodeficiency virus, hepatitis B virus, and hepatitis delta virus status and aminotransferase activities, histological activity index, alcohol consumption and the prevalence of cirrhosis were investigated. The patients included 54 homosexuals, 19 parenteral drug abusers and 187 subjects with other or unidentified risk factors for exposure to hepatitis B virus. Thirty-five patients (13%) were positive for antibody to human immunodeficiency virus; 27 were homosexual and 8 were drug abusers. The mean aminotransferase activities, histological activity index and the prevalence of cirrhosis were similar in the human immunodeficiency virus-positive and human immunodeficiency virus-negative subgroups. Actuarial survival was significantly lower in the human immunodeficiency virus-negative subgroups. Actuarial survival was significantly lower in the human immunodeficiency virus-positive group than in the human immunodeficiency virus-negative subjects (p = 0.004); the cause of death was clearly related to liver failure in four of the five human immunodeficiency virus-positive patients and two of the six human immunodeficiency virus-negative subjects who died. To evaluate the factors determining the severity of liver disease, we compared homogeneous subgroups of subjects. Among the homosexual patients, the prevalence of HBeAg and hepatitis B virus DNA, aminotransferase activities and the histological activity index did not differ according to human immunodeficiency virus antibody status.(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
Clinical significance of the polymerase chain reaction (PCR) assay in chronic HBV carriers.
PCR was evaluated as a clinical tool for use in accurate identification of the specific etiologic agent in chronic HBV carriers. The method was found to be valuable in diagnosis and for monitoring therapy, as well as for elucidation of genotypic variants of HBV in chronic HBV cases. By this means an HBV defective variant with alterations in the preS1/preS2 sequence was detected and is consequently described here.
Asia, Southeastern↗
Expression of insulin-like growth factor II (IGF-II) and IGF-II, IGF-I and insulin receptors mRNAs in isolated non-parenchymal rat liver cells.
The insulin-like growth factor II (IGF-II) is involved in embryonic growth. Modifications of its expression might play a role in the development of primary liver cancer in humans and woodchucks. In the liver, little information is available on the cell types involved in its synthesis. We have investigated the expression of IGF-II as well as IGF-II, IGF-I and insulin receptor mRNAs in non parenchymal liver cell preparations in rats of various ages. The results indicate that Kupffer cells, endothelial cells and fat-storing cells express both IGF-II and the three different receptor mRNAs. Furthermore, a switch from a fetal to an adult IGF-II mRNA profile was obtained in the different cell preparations. Therefore, our results indicate that regulation of IGF-II gene expression can be analyzed through these isolated liver cell preparations. These results might also be important in investigating the potential role of IGF-II in liver carcinogenesis.
Animals↗