Anti-pre-S2 antibodies in natural hepatitis B virus infection and after immunization.

Anti-pre-S2 antibodies were detected by enzyme-linked immuno-absorbant assay using a synthetic peptide analogue of pre-S2 protein, in different groups of hepatitis-B-infected subjects, including patients presenting with cirrhosis and liver cancer, and also in infants immunized with hepatitis B vaccine. Anti-pre-S2 antibodies were not detected in hepatitis B surface antigen (HBsAg) chronic carriers, including patients with cirrhosis or primary liver cancer. Anti-pre-S2 antibodies were not detected in HBsAg-positive sera during the early phase of acute hepatitis. They were only noted upon recovery, when anti-HBs antibodies are detectable at the same time as HBsAg. After recovery, anti-pre-S2 antibodies were noted in 57% of test sera and were still detectable in 16% of anti-HBs-positive sera obtained years after HBV infection. Anti-pre-S2 antibodies were detected in 70% of infants immunized with 2 or 5 micrograms doses of Hevac B Pasteur vaccine, confirming that this vaccine contains pre-S2 antigen. Anti-pre-S2 detection was correlated with the anti-HBs antibody titre.

HBsAG positive reactivity in man not due to hepatitis B virus.

A viral infection characterised by serum HBsAg positivity with serum anti-HBc negativity has been encountered in Senegal. The infection is not associated with the presence of HBeAg, so it differs from hepatitis B virus in its core antigen, but the surface antigen of the two viruses share some epitopes. After the loss of HBsAg, neither anti-HBc nor anti-HBs becomes detectable. Anti-HBs, naturally acquired or produced by immunisation, does not protect against this new infection. Chronic carriage occurs. If this new infection is confirmed to cause chronic liver disease, hepatitis B vaccine should include surface antigen from the new virus.

Persistence of circulating complexes between HBsAg and immunoglobulin M in sera of hepatitis B surface antigen positive patients suffering from liver cirrhosis or primary liver cancer.

Complexes between hepatitis B surface antigen (HBsAg) and immunoglobulin M (IgM) have been detected in acute type B hepatitis. Sequential serum testing for the presence of these complexes has been shown to be the best method for predicting disease chronicity. The presence of HBsAg/IgM complexes was investigated using an enzyme-linked immunosorbent assay with selected sera from Senegal. The three population groups studied were composed of 405 Senegalese soldiers as well as 84 liver cirrhosis and 169 primary liver cancer patients. Only one of the 122 HBsAg negative sera tested was found to be positive for HBsAg/IgM complexes. Complexes were detected 13.9% of the HBsAg positive soldiers, in 40% of the HBsAg positive liver cirrhosis patients, and in 50% of the HBsAg positive primary liver cancer patients. HBsAg/IgM complexes were also detected in 53.6% of the hepatitis B e antigen (HBe) positive soldiers, compared to 75 and 76% for the HBeAg positive liver cirrhosis and primary liver cancer patients, respectively. In anti-HBe positive sera, an increased proportion of HBsAg/IgM complexes was observed during the sequence chronic hepatitis (5%)-cirrhosis (29%)-primary liver cancer (42%). On the other hand, it has been reported that in the sequence of events leading from chronic hepatitis to primary liver cancer, there is an increase in anti-HBeAg prevalence and in alpha-fetoprotein levels. In this study, only alpha-fetoprotein levels were found to increase. Values higher than 15 IU/ml were observed in 4.3, 27.3, and 86.4% of the HBsAg positive individuals from the three groups. No significant variation was observed in the anti-HBe prevalence between the population group (64-75%).

Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen.

We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary.

Simultaneous administration of diphtheria/tetanus/pertussis/polio vaccine and hepatitis B vaccine in a simplified immunization programme.

In most developing countries hepatitis B virus is endemic and prevention has to be carried out early in life and on a mass scale. In these regions, simultaneous administration of multiple antigens is normal practice. We have therefore, investigated the interaction of hepatitis B vaccine with DTP-Polio vaccine. Studies include the immune response post one and two injections to diphtheria and tetanus toxoid, pertussis and hepatitis B surface antigen. The vaccines were given simultaneously or not at a 6 months interval. The immune response to HBsAg vaccine and DTP-Polio vaccine injected simultaneously was equal to the immune response observed after administration of vaccines alone. Moreover, no adverse reactions were noted. This trial also demonstrated that immunization with two doses of DTP-Polio vaccine, containing 30 Lf of diphtheria and tetanus toxoids, at a 6 months interval is sufficient to obtain a very good immune response.

[Hepatitis B and primary cancer of the liver in intertropical Africa]. / Hépatite B et cancer primitif du foie en Afrique Intertropicale.

During the past 15 years, a growing body of evidence incriminates hepatitis B virus as the major factor in the etiology of primary liver cancer. Epidemiological studies throughout the world reported a striking correspondence between areas where the frequency of primary liver cancer is high and where HBV infection is hyperendemic. Moreover, primary liver cancer is commonly associated with cirrhosis of the postnecrotic macronodular type. Such data suggested a sequence hepatitis-cirrhosis-PLC. Such sequence was confirmed by extensive serologic testing studies which reported a high frequency of HBV markers in PLC patients compared to matched control groups. Data collected in Senegal, Mali and Burundi on 12,000 individuals stress the importance of HBV infections in these countries, as the high rate of chronic carrier state in patients suffering from liver cirrhosis or primary liver cancer (62-63%) compared to the general population (12-17%). Other HBV markers including anti-HBs, anti-HBc, HBeAg and anti-HBe had no prognostic value in the sequence hepatitis-cirrhosis-PLC. A new HBV seric marker, the HBsAg/IgM complexes, observed in HBsAg positive individuals, is more frequently detected in PLC patients (50%) and cirrhosis (40%) than in healthy HBsAg carriers (14%). These results would indicate that HBsAg carriers are more likely to develop cirrhosis or primary liver cancer when they evidence HBsAg/IgM complexes. In conclusion, the seric markers of evolution towards primary liver cancer are: HBsAg (the highest known risk factor), the presence in such individuals of HBsAg/IgM complexes, and increased values of alphafoetoprotein.

Hepatitis B virus serological markers in Africans with liver cirrhosis and hepatocellular carcinoma.

Serum samples were collected at the time of hospitalization from 221 black Africans suffering from cirrhosis and 453 suffering from hepatocellular carcinoma (HCC). These patients came from Senegal, Burundi and Mali, and 6655 adults from different population groups in these countries were used as controls. Hepatitis B virus (HBV) serum markers, including hepatitis B surface antigen (HBsAg), anti-HBs, antibody to hepatitis B core antigen (anti-HBc), HBeAg and anti-HBe, were determined by radioimmunoassay, while alpha-fetoprotein and complexes between HBsAg and IgM were detected by ELISA tests. HBsAg was detected in 11.8-17.6% of controls as opposed to 63.3% of patients suffering from cirrhosis and 62.7% of patients suffering from HCC. There was less evidence for HBV replication in cirrhosis and HCC in older patients. A significant increase in the frequency of HBsAg/IgM complexes was found in passing from the HBsAg chronic carrier state (13.9%) to cirrhosis (29.9%) and finally to HCC (33.7%).