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Biomedical subjects

P Roingeard

Publications and source records attributed to P Roingeard.

35 records · Page 2Linked to original sources
PubMed1995

Hepatitis B, C, D, and E markers in rural equatorial African villages (Gabon).

Serologic markers of hepatitis B virus (HBV), including HBV DNA, and of hepatitis delta virus were measured in three villages in Gabon. Of 303 subjects studied, 19% were carriers of hepatitis B surface antigen (HBsAg); 8.5% of these had anti-delta antibodies. No difference among the three villages was observed. All HBV DNA carriers were children less than 11 years of age. In the 2-9-year-old group, 71% of the HBsAg-positive children tested were HBV DNA carriers. These results indicate that HBV prevalence is high in Gabon and emphasize the importance of horizontal transmission of HBV in Africa. Antibodies to hepatitis C virus, assessed in one of the three villages, were found with a prevalence of 35% with a second generation enzyme-linked immunosorbent assay (ELISA) and 24% with a third generation ELISA. None of 35 subjects tested for antibodies to hepatitis E virus was positive.

Adolescent↗
PubMed1994

Serum alanine aminotransferase measurement as a guide to selective testing for hepatitis C during medical checkup.

The efficiency of elevated serum alanine aminotransferase values for selecting subjects to be tested for hepatitis B or C infections in a large French population undergoing a medical checkup was investigated. For 5 consecutive weeks, serum alanine aminotransferase values were controlled in 9044 subjects; 308 subjects (202 males) were selected with alanine aminotransferase levels 1.2-fold above the normal value (58 iu/l for men, 34 iu/l for women). For each selected case, an age- and sex-cross-matched control was included. Of the 308 subjects with elevated alanine aminotransferase values, one was HBsAg positive and 15 (seven males) were anti-HCV positive. All anti-HCV sera tested by enzyme immunoassay were also positive by three immunoblots and 11/15 (73%) were HCV-RNA positive by reverse transcription-polymerase chain reaction. Of the 308 control subjects, two were HBsAg positive and four (two males) were weakly anti-HCV positive by enzyme immunoassay. Only one weakly anti-HCV positive serum was reactive by one immunoblot and all were HCV-RNA negative. This study shows the usefulness of alanine aminotransferase screening to detect hepatitis C virus infection in the general French population. Many of the anti-HCV positive subjects detected in this study were not aware of their hepatitis C virus seropositivity (12/15) or that they were viremic (11/15). Use of this low-cost assay will considerably reduce the number of subjects to be tested for hepatitis C virus serological status and therefore the cost. It may make possible the investigation of large populations by setting up public health programs to detect and treat hepatitis C virus. Hepatitis C virus infected subjects detected in these programs could benefit from medical follow up, including antiviral therapy.

Adolescent↗
PubMed1994

Influence of human immunodeficiency virus infection on hepatitis delta virus superinfection in chronic HBsAg carriers.

It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis delta virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV, HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during delta virus superinfection in HDV-positive, chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-delta antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis delta antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0%; P = 0.01), while markers of HDV replication (serum anti-HD IgM, serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50%, respectively) as in those who were HIV-negative (75%, 52% and 30%, respectively; P > 0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 +/- 3.2) and HIV-negative (10.7 +/- 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM. HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear); (3) the histological severity of liver disease is not influenced by HIV status.

Adult↗
PubMed1993

Perinatal transmission of hepatitis B virus in Senegal, west Africa.

We studied 152 healthy pregnant women and their 156 newborns for markers of hepatitis B virus (HBV) infection in Dakar, Senegal. Of these, 120 mothers (79%) had antibodies to the hepatitis B core antigen (anti-HBc), 21 (13.8%) were hepatitis B surface antigen (HBs Ag) positive, including 2/21 (9.5%) hepatitis B core-associated antigen (HBe Ag) positive and 1/21 (4.7%) HBV DNA positive. At birth, 11 (7%) infants were HBs Ag positive; 9/11 had an HBs Ag positive mother. Ten of these HBs Ag positive-born infants were investigated at 6-7 months: 5 were strongly HBs Ag positive and developed antibodies to HBs Ag, HBc Ag or HBe Ag; these 5 (3.2% of the total) probably became chronic carriers of HBV. The 5 others were HBs Ag negative and 4/5 did not develop antibodies against HBV Ag; HBs Ag positivity at birth was likely due to contamination of the mother's blood. Thirty-one of the 145 HBs Ag negative-born infants were studied at 6-7 months and remained HBs Ag negative. However, 5 (16%) showed evidence of HBV infection occurring between 0 and 6 months, as shown by the development of antibodies to HBs Ag, HBc Ag, and/or HBe Ag. Despite the low prevalence of HBV DNA and HBe Ag in HBs Ag positive African mothers, this study shows the occurrence of perinatal transmission of HBV in West Africa, in contrast with previous studies. Perinatal HBV transmission could explain the HBV vaccination failure recently reported in children in Senegal.

Carrier State↗
PubMed1993

Characterization of RNA-binding domains of hepatitis delta antigen.

Hepatitis delta antigen (HDAg), the only protein encoded by the hepatitis delta virus (HDV), binds specifically genomic and antigenomic strands of the HDV RNA. In a previous study, three recombinant HDAg subdomains were synthesized, covering residues 11 to 78, 79 to 163 and 164 to 212, and only the middle domain was shown to be responsible for the binding to HDV RNA. To investigate HDAg sequences involved in HDV RNA binding, we synthesized five peptides, 15 to 29 residues in length, and tested their ability to bind HDV RNA using a simple non-radioactive ELISA with digoxigenin-labelled HDV genomic or antigenomic RNA probes. The specificity of interactions was demonstrated by comparison with control peptides and non-HDV RNA probes, and with an inhibition assay using recombinant HDAg. The HDAg-binding domain found within the middle region (79 to 163) of HDAg was more finely mapped: it is located between residues 79 and 107. In addition, another domain (residues 2 to 27) of HDAg was also found to bind specifically to HDV RNA. These two peptides share sequence similarities at residues 2 to 10 and 97 to 107 with other RNA-binding domains.

Amino Acid Sequence↗
PubMed1993

Immune response to synthetic peptides of hepatitis delta antigen.

Hepatitis delta antigen (HDAg) is the only viral protein known to be expressed during hepatitis delta virus (HDV) infection. Detection of antibody to HDAg (anti-HD) is the usual method for diagnosis of HDV infection since viremia lasts only a few weeks. In an effort to identify the major epitopes recognized by humans during natural infection, four oligopeptides including residues 2 to 17 (SP1), 155 to 172 (SP2), 168 to 182 (SP3), and 189 to 211 (SP4) of the HDAg molecule were synthesized and probed by enzyme-linked immunosorbent assay with a panel of 80 serum specimens from 45 patients suffering from either HDV-hepatitis B virus coinfections (n = 17) or HDV superinfections (n = 28). Sera from infected patients recognized these relatively short peptides. Peptide SP2 was the most antigenic; 71% of serum specimens reacted. Antibody to SP2 was also the commonest in sera taken early in the course of the disease. Peptide SP2 corresponds to one of the two regions which is highly conserved between different isolates. Among the 63 serum specimens which scored anti-HD positive by a commercial assay, all but 3 reacted to at least one of the peptides (95% agreement). Peptide assays appeared to be significantly more sensitive than the commercial assay with native HDAg early in the course of HDV infection since 14 of 17 (82%) serum specimens which scored anti-HD negative in the commercial assay reacted to one or more peptides. All serum specimens giving one or more positive results with the various peptides were confirmed as being HDV positive by an inhibition assay with free peptide in solution. The immune response to HDAg peptides vared greatly between individuals. No specific reactivity profile could be assigned to those with either HDV-hepatitis B virus coinfections or HDV superinfections. Overall, HDAg peptides appeared to be convenient reagents in addition to native antigen for the development of new and improved diagnostic tests for HDV infection.

Amino Acid Sequence↗
PubMed1992

Persistent delta antigenaemia in chronic delta hepatitis and its relation with human immunodeficiency virus infection.

The prevalence of persistent hepatitis delta (HD) antigenaemia and associated factors in patients with chronic infection with the hepatitis delta virus (HDV) were investigated. Among 157 consecutive patients known to be carriers of hepatitis B surface antigen (HBsAg), 36 (23%) had one serum marker of HDV infection (anti-HD and/or HDAg). Nine of the patients with an HDV marker were HDAg positive, including three who were anti-HD negative. A follow-up over a mean period of 13 months showed that five of five patients had a persistent HD antigenaemia. This serological profile was associated with the presence of antibody to the human immunodeficiency virus (anti-HIV) (P < 0.01), serum HIV antigen (HIVAg) (P < 0.2), and the female sex (P < 0.05). Persistent HD antigenaemia could be the consequence of the suppression of T cell cytotoxic activity against hepatocytes expressing HDAg, a lower humoral response, and/or hormonal factors.

Adult↗
PubMed1992

Infection due to hepatitis delta virus in Africa: report from Senegal and review.

A review of the literature shows strong variations in the prevalence of hepatitis delta virus (HDV) among Africans seropositive for hepatitis B surface antigen (HBsAg). In Senegal, West Africa, prevalence of antibodies to HDV among asymptomatic HBsAg carriers appears to be linked to regional and/or socioeconomic factors. Antibodies to HDV were found in 22 (47%) of 47 HBsAg-seropositive patients with liver disease who were hospitalized in the main hospital of Dakar and in 4% to 44% of asymptomatic HBsAg carriers. Eight (36%) of 22 patients with liver disease were seropositive for IgM antibodies to HDV, whereas none of 18 asymptomatic subjects were seropositive (P less than .01). According to studies conducted in Europe and the United States, the presence of this marker may constitute support for the argument that HDV plays a role in the development of HBsAg-associated liver diseases in Senegal and, presumably, within the African continent.

Adult↗
PubMed1990

Immunocytochemical and electron microscopic study of hepatitis B virus antigen and complete particle production in hepatitis B virus DNA transfected HepG2 cells.

The relationship between the presence of hepatitis B virus antigens, their localization and hepatitis B virus replication was studied in different clones of cultured HepG2 hepatoblastoma cells transfected with cloned hepatitis B virus DNA. Intracellular hepatitis B virus antigens were detected by immunofluorescence. The production of these antigens was evaluated in the culture media by enzyme-linked immunoassay. Hepatitis B virus DNA was detected using dot-blot hybridization. Three types of HBcAg staining were observed in transfected HepG2 cells: (a) cells with nuclear HBcAg, (b) cells with cytoplasmic HBcAg and (c) cells with both nuclear and cytoplasmic HBcAg. Cell types b and c also expressed hepatitis B virus DNA in their culture media. Our results suggest that cytoplasmic HBcAg may be more involved than nuclear HBcAg in hepatitis B virus replication. The site of hepatitis B virus formation in hepatocytes was studied by electron microscopic examination of a specific hepatitis B virus producer clone, thereby allowing detection of intracellular Dane particles more easily than liver biopsy samples from infected patients. Dane particles and HBsAg filaments were found in large, dilated structures probably related to the endoplasmic reticulum. Budding of core particles into cisternae of endoplasmic reticulum-related structures appears to be a possible mechanism for hepatitis B virus formation; our results suggest that the exocytosis of cisternae to extracellular spaces may be a mechanism for release of hepatitis B virus particles.

Blotting, Southern↗
PubMed1990

Hepatitis B virus core antigen (HBc Ag) accumulation in an HBV nonproducer clone of HepG2-transfected cells is associated with cytopathic effect.

Two clones of the hepatoblastoma HepG2 cell line transfected with complete hepatitis B virus deoxyribonucleic acid (HBV DNA) were studied. The kinetics and cytopathic effect of HBV Ag production in these two clones (one of which was an HBV producer) were compared to those of the parent HepG2 cell line. The presence of hepatitis B surface antigen (HBs Ag) and hepatitis B e antigen (HBe Ag) was determined by commercial enzyme-linked immunosorbent assay (ELISA). A hepatitis B core antigen (HBc Ag)-specific ELISA assay was developed, using monoclonal anti-HBc to detect HBc Ag. Amounts of HBs, HBe, and HBC Ags were partially quantified in both intracellular and extracellular compartments. The HBV producer clone excreted high levels of HBc, HBe, and HBs Ags from the beginning of the growth phase, and no cytopathic effect was observed. The HBV nonproducer clone produced high levels of HBs and HBe Ags, but there was no detectable HBc Ag in the supernatant; instead, HBc Ag accumulated in the intracellular compartment. In this clone, significant cell death was observed 4 days after cell confluency, corresponding with notable HBc Ag release into the supernatant. These results suggest a cytopathic effect associated with HBc Ag accumulation in the HBV nonproducer clone, but no cytopathic effect in the HBV producer clone. This suggests that virological factors as well as the host's immune response may be considered in explaining liver injury occurring in hepatitis B.

Carcinoma, Hepatocellular↗
PubMed1989

Hepatitis delta virus infection in French male HBsAg-positive homosexuals.

The prevalence and serological features of hepatitis delta virus infections were studied in a French population of chronic, non-drug addict, hepatitis B surface antigen carriers: 42 male homosexual patients were compared to 30 nonhomosexuals (20 who evidently had not been exposed to any of the usual hepatitis B virus-hepatitis delta virus risk factors and 10 hemodialyzed patients or kidney allograft recipients). Six of the 42 male homosexuals (14.3%) had at least one serological marker of hepatitis delta virus infection (hepatitis delta antigen, total and/or IgM anti-hepatitis delta antibodies). Serological follow-up was obtained for five of these patients over several months and confirmed the chronicity of the delta infection in at least four of the five subjects. Hepatitis delta antigen and hepatitis delta virus RNA were found in the liver and in the serum, respectively, of four of the five tested patients. Hepatitis B virus DNA was negative in the serum of five of the six hepatitis delta virus-positive homosexuals vs. only eight of 35 hepatitis delta virus-negative homosexuals (p less than 0.02). Human immunodeficiency virus was negative in all of the nonhomosexuals; its prevalence did not differ between the hepatitis delta virus-positive and -negative homosexuals: three were human immunodeficiency virus-positive among the six former vs. 15 among the 36 latter. Human immunodeficiency virus positivity was without obvious influence on hepatitis B virus replication, since among 35 hepatitis delta virus-negative homosexuals hepatitis B virus DNA was found in 80% of the human immunodeficiency virus-positive individuals and 70% of those who were human immunodeficiency virus-negative.

Adult↗
PubMed1988

[Serologic diagnosis and epidemiology of acute delta hepatitis in Indre-et-Loire].

A 6 years retrospective study (1981-1986) of 153 consecutive cases of HBsAg positive acute hepatitis was carried out to assess the prevalence of delta virus infections in the Indre-et-Loire a district of the Loire Valley in France. Diagnostic value of the various serum markers of delta infection, i. e. HDAg, anti-HD and anti-HD IgM, were evaluated using immunoenzyme assays. During the survey, 22 cases of delta hepatitis were diagnosed (12 co-infections, 10 superinfections). They all involved young adults, 21 of them were drug-addicts, and one young woman was the consort of a drug-addict. In Indre-et-Loire, delta virus infection was responsible for half of acute HBsAg positive hepatitis among drug-users in the last 3 years of our study. Clinical and biological features of acute delta hepatitis were compared to those of the other HBsAg positive hepatitis: two cases of fulminant hepatitis occurred among the 12 co-infections; 4 of 6 superinfection that could be followed up to 6 months developed biopsy-proven chronic active hepatitis. Delta Ag was found constantly during the first week of the disease, its disappearance was always followed by a seroconversion to anti-HD after four weeks. Anti-delta IgM was an inconstant and late marker: it was detected within the first 4 weeks in only one case (a co-infection); it persisted only in superinfections. Our study shows that delta Ag is an efficient serum marker for the early diagnosis of acute delta hepatitis.

Acute Disease↗