Carriage of HBs antigen in New Caledonia. Study according to ethnic group

Owing to 2,772 New Caledonian blood donors and pregnant women, a study was made of the salient features of the H. B. s. antigen carrier state; percentages of carriers showed no difference according to the age and a slight difference between sexes. These percentages proved to be quite different according to ethnic groups. Smaller rates of carriers were found among Europeans (1.1%) than among Melanesians (7.6%) as well as Polynesians (7.7%). There is a relation between H. B. s. carrier state and positive treponema serology, the latter occurring more frequently among melanesian and polynesian groups.     

Markers of hepatitis-viral infection in children born of mothers with hepatitis B

Sixty-two women suffering from hepatitis B (HB) and their newborn babies were examined by a highly sensitive radioimmunoassay (RIA). The fluorescent antibody technique was also used to examine autopsy specimens of livers of 7 fetuses, 1 stillborn, and 3 babies dying in the first days of life whose mothers during pregnancy or delivery had experienced HB. Frequent infection of babies (77.8%) was observed at high concentrations of HBsAg in mothers in labor with subsequent development of persisting HBs-antigenemia, and in half of the babies of chronic hepatitis. HBsAg was detected in the first days of life not only in the blood serum, but also in the liver tissue which may be explained by intrauterine infection. At low concentrations of HBsAg in mothers the babies were infected less frequently (26.1%) and half of them were shown to have anti-HBs in the umbilical blood and blood serum in the first days and months of life. Anti-HBc transmission from mothers was also demonstrated. In babies born to convalescents after HB in the absence of HBsAg, anti-HBs in combination with anti-HBc were determined.     

Delayed visuomotor development in children born to adolescent mothers

The objective of the present study was to determine visuomotor development of children born to adolescent mothers and to compare it with that observed in those born to adult mothers. The sample included 59 urban Mestizo children, 7–8 years of age, who were born to adolescent mothers, and 73 urban Mestizo children of the same age, who were born to adult mothers (>20 years). Visuomotor development was assessed using the Bender test. Children born to adolescent mothers had a higher number of errors in the Bender Gestalt scores compared to those obtained by children born to adult mothers. Items of perseverance and integration in the Bender-Gestalt test were the most affected in children born to adolescent mothers. Of the children born to adolescent mothers, 13.8% repeated a school grade compared to 4.3% of children born to adult mothers (P < 0.01). Differences in sociocultural circumstances between the adolescent and adult mothers may have influenced the results. Nevertheless, children born to adolescent mothers have delayed visuomotor maturation and a low performance at school. Am. J. Hum. Biol. 9:717–723, 1997. © 1997 Wiley-Liss, Inc.     

Staining method for hepatitis B surface antigen (HBs Ag) and its mechanism

HBs Ag in the hepatocytes has been stained by the orcein method. As degenerative and necrotic cytoplasms of hepatocytes are occasionally stained also by this method, it is difficult to identify HBs Ag. The orcein dye has different staining properties from lot to lot, causing difficulty in obtaining stable results. Therefore, the author tried to modify the orcein method and found that the procedure using a sensitizer (ferric ammonium sulfate or uranium nitrate) after oxidizing the solution gave stable and satisfactory results. By this method, in the hepatocytes, only HBs Ag is stained positively. The mechanism of function of the sensitizer is not clear, but it is considered that ferric or uranium ions occupy small gaps in the protein molecular structure in the cells before orcein molecules occupy these gaps and that the method does not give any false positive result. It is also suggested that various HBs Ag staining dyes can react with sulfonic acid residue groups which are formed by the oxidization of disulfide group of proteins. Another new staining method for HBs Ag using resorcin fuchsin has been developed. The results of this method were also discussed.     

Absence of hepatitis B virus (HBV) DNA in children born after exposure of their mothers to HBV during in vitro fertilization.

During in vitro fertilization, 22 human embryos were exposed to hepatitis B virus (HBV) in contaminated human serum present in the culture medium. All mothers experienced hepatitis B during the first trimester of pregnancy, and two had hepatitis B surface antigen and HBV DNA, as determined by PCR, at the time of delivery. No HBV DNA was found in serum or lymphocytes from the exposed 22 infants. HBV DNA was also absent from one infant at autopsy.     

Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis

Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long-term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving antiviral immunity. In particular, treatment with nucleoside analogs was found to increase CD40 ligand (CD40L; CD154) levels, an inducible molecule expressed on activated T lymphocytes. The present study investigated potential immunostimulatory effects of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving either ante- or postnatal therapy to reduce the transmission rate. To this end, we analyzed CD40L expression in unstimulated lymphocytes from peripheral blood samples of uninfected infants vertically exposed to HIV and subjected to ART. The CD45 PanLeucogating strategy was applied in flow cytometry to analyze the lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found increased CD154 expression on both CD4+ and CD8+ lymphocytes in ART-treated infants, compared with the controls. CD154 was apparently functional, because the expression of CD86 on monocytes was enhanced; moreover, inhibition of the CD40-CD40L interaction produced downmodulation of CD86. From these results, we conclude that CD4+ and CD8+ lymphocytes of HIV-exposed noninfected infants, who have been exposed to antiretroviral drugs in fetal and early life, display enhanced CD154 expression and costimulatory activity.     

A mathematical model predicting anti-hepatitis B virus surface antigen (HBs) decay after vaccination against hepatitis B

The determination of serum levels of antibodies against hepatitis B virus surface antigen (anti-HBs) after hepatitis B vaccination is currently the only simple test available to predict the decay of protection and to plan the administration of booster doses. A total of 3085 vaccine recipients of plasma-derived and recombinant vaccine have been followed for 10 years to determine the kinetics of anti-HBs production and to construct a mathematical model which could efficiently predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days after the last dose of recombinant vaccine and 138 days after the last dose of plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic mathematical model (log10 level, log10 time) of anti-HBs decay has been constructed on a sample of recombinant vaccine recipients and subsequently validated on different samples of recombinant or plasma-derived vaccine recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number of vaccine doses (three or four) did not influence the mathematical model of antibody decay. The program can be downloaded at the site: http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs determination obtained after the peak, the program calculates a prediction of individual anti-HBs decline and allows planning of an efficient booster policy.     

Development of anti-hepatitis B surface (HBs) antibodies after HBs antigen loss in HIV-hepatitis B virus co-infected patients

BackgroundHepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV.ObjectivesTo determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients.Study designPatients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation.ResultsFourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR = 1.1–5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57–1.93 year⁻¹ (population maximum growth rate = 1.02) and antibody production plateaued between 2.09–3.66 log₁₀ mIU/mL at the end of follow-up (population maximal antibody levels = 2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads (P = 0.03) and proportion with elevated ALT levels (P = 0.02) and HBeAg-positive serology (P = 0.08). No such differences were observed in those without HBsAg-seroconversion.ConclusionsMost co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection.     

Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers.

The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates, respectively. 58 infants who could not be vaccinated constituted the control group. It was observed that in the unvaccinated group approximately 70% of the infants became infected. In both the vaccinated groups, the seroconversion and seroprotection rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up, but, at 12 months, infants given HBIG and vaccine showed better seroprotection rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine was also better in both the groups if the mothers were anti-HBe positive. Despite immunization, 14.2% and 25% infants in group I and II, respectively, became chronic carriers if their mothers were HBeAG positive.     

Behavior and development patterns in children born to heroin-addicted and methadone-addicted mothers

This paper reviews the literature regarding the development of children up to age 6 years who were born to mothers addicted to heroin or methadone. These children are compared with children born to nonaddicted mothers to determine whether there were any differences between the two groups related to maternal drug addiction. This paper discusses the obstetrical and medical complications associated with maternal drug addiction and their effects on the prognosis of the infant at delivery.     

Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B

Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n = 52), immune clearance (IC group, n = 105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n = 97), HBeAg-negative quiescent group (ENQ group, n = 95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n = 55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r = 0.874, p <0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r = 0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r = 0.537, p <0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p <0.001) and HBsAg (5.05/5.96 log mIU/mL, p <0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.     

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009. © 2009 Wiley‐Liss, Inc.     

Study of antigen HBs and antivirus antibodies of hepatitis C during hepatopathies in Mali

A prospective study carried out in Bamako, Mali between July 1998 and January 1999 has assessed the seroprevalence of hepatitis C virus (HCV) in 91 carrier patients of chronic hepatopathy at a cirrhrosis stage (53) or of hepato-cellular carcinoma (38) and to compare with in 92 blood donors as a control population. Only seroprevalence confirmed by a complementary test has been taken into account (RIBA). HCV seroprevalence reached 25% including all hepatopathies, 24% in cirrhrosis and 26% in hepato-cellular carcinomae (HCC) versus 4% in blood donors. Antigen HBs of hepatitis B virus has been found in 55% of patients, versus 25% of the control cases (p = 0.0006). On the whole, the two markers have been notified a little more often in HCC than in cirrhosis and the combination of the two markers has been more frequent during cirrhosis as well. The role of HCV played in cirrhosis and HCC onset in Mali appears to be important.     

The variability of hepatitis B envelope is associated with HBs antigen persistence in either chronic or acute HBV genotype A infection

BackgroundMore than 240 million people are chronically infected by hepatitis B virus (HBV) worldwide. Envelope proteins play a crucial role in viral cellular entry and immune recognition. The loss of HBs antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved with or without treatment (3–16%).ObjectivesHBV envelope variability was investigated according to HBsAg persistence.Study designThe cohort consisted of 15 HBV genotype A-infected patients divided into “resolvers”, with HBsAg clearance, and “non-resolvers”, with HBsAg persistence and in subgroups: acute (n = 5, AHBV) or chronic infection (n = 4, CHBV) and HBV/HIV coinfection (n = 6, CHBV/HIV). HBV S and preS sequences were studied by direct and ultra-deep sequencing. Amino acid sequences were analyzed with bioinformatics for predicted antigenicity.ResultsIn S gene, the complexity was lower in AHBV than in chronic-infected patients (p = 0.046). Major mutations, detected using direct sequencing, were more frequent in AHBV developing chronicity (p = 0.01) than in AHBV resolvers. In the Major Hydrophilic Region, more frequent mutations were observed in non-resolvers versus resolvers (p = 0.047) and non-resolvers tended to have more haplotypes with a reduced predicted antigenicity (p = 0.07). Most of the mutations in preS/S region were found rather in epitopic than in non-epitopic areas (p = 0.025). Interestingly, the mutation sY161F found in 3/8 non-resolvers was associated with a decrease in predicted antigenicity (28%; AnTheProt).ConclusionsHBsAg persistence was correlated with mutations and deletions in areas playing a key role in immune recognition. These data suggest that variability in HBV envelope could favor immune escape in various clinical settings of HBV genotype A-infected patients.     

Use of hepatitis B virus DNA quantitation to predict hepatitis B e antigen reversion in cases of chronic hepatitis B

Seventy-three chronic hepatitis B patients who had either hepatitis B e antigen (HBeAg) seroconversion (group I) or HBeAg-negative disease (group II) were studied. HBV DNA levels at HBeAg seroconversion (group I) and at initial visits (group II) were significantly lower among patients who were persistently negative for HBeAg than among those who underwent HBeAg reversion.