Biomedical subjects
Publications and source records attributed to A Goudeau.
Hepatitis B core antigen was demonstrated in the hepatocytes of 28 of 40 patients with chronic active hepatitis in whose sera hepatitis B surface antigen was not detectable by radioimmunoassay. This finding suggests that in these patients, despite hepatitis B surface antigen being undetectable in serum, the liver disease is the consequence of chronic infection with hepatitis B virus.
Clinical observations of patients with primary hepatocellular carcinoma (PHC) at Le Dantec Hospital, Dakar, Senegal, were studied to determine a correlation with hepatitis B virus (HBV) infection. Of the 103 patients with PHC, 80 had an active HBV infection (HBsAg and/or anti-HBc); 23 showed signs of previous HBV infection (anti-HBs and anti-HBc). The two groups were similar in the detection of alpha-fetoprotein (approximately 60%) and in the major clinical findings: hepatomegaly, 76.25% and 86.96%, respectively; and ascites, 57.50% and 47.83%, respectively. Jaundice, however, was three times more frequent (P < 0.01) in the group of patients with signs of active HBV replication. Distribution of HBV markers as a function of age at onset of PHC revealed that the presence of HBsAg was primarily confined to the sera of the younger patients (< 50 yr old). When compared with leprosy patients and blood donors, the younger PHC patients differed in the frequency of detection of HBsAg and anti-HBs. The older people (> 50 yr old) in the three groups (PHC patients, leprosy patients, and blood donors) had identical HBV markers.
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The frequency of inapparent hepatitis A infection estimated by the detection of IgM anti-HAV in the absence of clinical signs, was found to be very low in two institutions for children. Only 15.4% of the infections are inapparent in department of pediatric psychiatry. Thus, poor hygienic conditions resulting in frequent and massive fecal-oral infections might lead to an increased number of overt hepatitis A infections.
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The presence of hepatitis B virus (HBV) antigens was examined in specimens of liver tissue obtained at necropsy from black Senegalese patients suffering from primary hepatocellular carcinoma (PHC). The results were correlated with markers of hepatitis B infection in serum. Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) were sought for in 15 liver extracts. HBsAg was found in the liver in 10 of 12 cases with HBsAg-positive serum. HBcAg was detected in three livers. The HBsAg was detected in seven of eight livers by immunofluorescence and orcein staining. HBsAg-positive cells were mainly located in the peri-tumoral cirrhotic tissue, although positive hepatocytes were also found in tumour nodules in liver from one of the patients. HBcAg was found in five of seven cases by immunofluorescence in hepatocytes of the cirrhotic areas. HBcAg fluorescence was primarily nuclear but, in some lobules, a patchy cytoplasmic fluorescence was observed. This suggests a cytoplasm-nucleus pathway in the synthesis of the HBV core antigen. Electron microscopy was performed on two HBsAg- and HBcAg-positive cases. Fibrillar and crystalline cytoplasmic inclusions were observed in tumour cells. In the same cells, 20-25 nm virus-like particles were present in swollen cisternae of the endoplasmic reticulum.
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The hepatitis B virus markers were studied on 553 leprous sera and 100 controls sera. HBs Ag detected by RIA were present on 25,4% of leprous and 12% of controls; the anti-HBs by RIA were revealed in 44,1% of patients out 38% of controls. The leprous was not carrying this markers were HBe Ag or anti-HBe or anti-HBc positive. By this vertical study it appears that 2,4% of the cases presented recent or acute hepatitis; 23% were chronic carriers; 41,7% had been in times past infected but were cured and the third remaining had been infected but coat markers were absent, it is more than likely that is an old infected group. The study revealed no significant difference in hepatitis chronic forms frequency between lepromatous and tuberculoïd patients.
The prevalence of antibody to the hepatitis A antigen (anti-HAV) has been studied in Senegal, among patients suffering from primary hepatocellular carcinoma (PHC) and among healthy blood donors. Anti-HAV was found in 62.5% of 64 cases of PHC as compared to 64% of 50 blood donors. Anti-HAV was as prevalent among PHC patients who evidenced chronic hepatitis B infection as among those without markers of chronic hepatitis B infection. These data suggest that hepatitis A infection is not associated with PHC in Senegal.
The development of a vaccine against hepatitis B prepared with purified and inactivated HBs Ag is described. This vaccine has been applied in patients and staff members of haemodialysis centres. Safety and efficiency of the vaccine are very satisfactory. The response of patients to immunisation was significantly lower compared to the response of the staff members. None of the volunteers who had a primary response to immunisation developed signs of clinical or biological hepatitis.
Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV). A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsAg-positive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to persistent infection with hepatitis B virus. Epidemiological clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa.
Antibody to hepatitis B core antigen (anti-HBc), which has been assumed to be a more sensitive indicator of hepatitis B virus replication than hepatitis B surface antigen (HBsAg), was detected in the sera of 26 of our 65 patients with HBsAg-negative chronic active hepatitis. Thus despite the absence of HBsAg the liver disease could be the consequence of chronic infection with hepatitis B virus in these patients. They differed, however, from a group of 35 patients with HBsAg-positive hepatitis in being older on average and having less active liver lesions. The two groups could represent either two stages of chronic infection with hepatitis B virus or two types of response to it.
Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization. Tumours from two of three patients with a current HBV infection contained 1--2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen-positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti-HBs contained no detectable HBV DNA. A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models.
A study of the serological markers of Hepatitis B virus (HBV) including e antigen (HBe Ag) and antibody against HBe Ag (anti-HBe) was performed in Senegalese patients suffering from cirrhosis and primary hepatocellular carcinoma, and in a control group (blood donors). It was not possible to diagnose additional HBV infections in primary hepatocellular carcinoma patients using HBe Ag or anti-HBe Ab alone as serological markers. The lower prevalence of HBe Ag among primary hepatocellular carcinoma patients as compared with cirrhotic patients suggests that active replication of HBV becomes increasingly defective during the course of the malignant process.
A formalin-treated hepatitis B vaccine in the form of purified hepatitis B surface antigen (HBsAg) was prepared from asymptomatic human HBsAg carriers. Its safety and potency were tested in 5 chimpanzees. The vaccine was administered to 264-individuals. The results of the first 173 immunizations--46 hemodialysis patients and 127 staff members--are presented. Potency was ascertained and efficacy assessed by the development of humoral immune responses to HBsAg (anti-HBs antibody) and seroepidemiologic studies of vaccinated and nonvaccinated subjects. The results, 2 years after immunization, suggest that the vaccine was protective against hepatitis B infection in high-risk hemodialysis settings. Preliminary studies with an inactivated hepatitis B vaccine similarly prepared, but with aluminum hydroxide as adjuvant, indicate that a such a preparation induces a more rapid and stronger anti-HBs response.
In October 1975, a specific immunization by means of a formalin inactivated hepatitis B vaccine has been introduced to protect patients and staff members of three haemodialysis units of the Loire Valley (Tours, Blois, Orléans). After two years follow-up the innocuity and efficacy of this preparation have been shown to be very satisfactory in the conditions under which it was used. A method of vaccine preparation has been instituted in the development of industrial batches of vaccine to be used for broad clinical trials in France. The HBsAg purification was carried out by four different steps including, successively, selective adsorption-desorption on colloidal silicate (Aerosil), precipitations by polyethylene glycol, gel filtration and finally zonal ultracentrifugation. Step-by-step results of the purification are presented. Up to 65 % of the starting antigen was recovered at the end of the purification process. One dose of vaccine (1 ml) has a titre in HBsAg of 1/4 in countercurrent electrophoresis and a protein amount of 2-10 micron/ml. It contains traces of homologous serum proteins only detectable after high concentration. Purity, antigenic quality and safety of the vaccine are analysed in regards to its use for immunization against hepatitis B in man.
During 1976, two hepatitis A epidemics in institutions enabled the authors to study the presence of the virus in the faeces during the course of the disease. After concentration of feacal extracts in polyethyleneglycol 6000, virions were observed by immune electron microscopy. Among 13 stool extracts examined, 11 proved positive. The two negative extracts were samples collected one month after the onset of clinical symptoms and signs. The samples richest in particles were those collected during the preicteric phase of the disease. In those cases in which samples were collected during jaundice, the viral concentration was lower. The limit of detection was a period of five days after the onset of jaundice. Thus, examination for hepatitis A virus in the faeces by electron microscopy may be used to obtain an aetiological diagnosis at the beginning of the disease. In one of the patients, a study of the kinetics of the appearance of antibodies was possible. From the time of onset of jaundice, the presence of specific antibodies was noted, reaching a maximum after two months. In the children's institution, no cases of hepatitis A were seen among those entrants who had received an injection of standard polyvalent gammaglobulin at the time of admission.
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