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Biomedical subjects

M Rizzetto

Publications and source records attributed to M Rizzetto.

At least 271 records · Page 15Linked to original sources
PubMed1986

Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope.

Hepatitis delta virus (HDV)-associated particles were purified from the serum of an experimentally infected chimpanzee by size chromatography and by density centrifugation. Hepatitis delta antigen (HDAg) was detected after mild detergent treatment at a column elution volume corresponding to 36-nm particles and banded at a density of 1.25 g/ml. The serum had an estimated titer of 10(9) to 10(10) HDV-associated particles and had only a 10-fold excess of hepatitis B surface antigen (HBsAg) not associated with HDAg. Therefore, HDV appears to be much more efficiently packed and secreted than is its helper virus, hepatitis B virus (HBV), which is usually accompanied by a 1,000-fold excess of HBsAg. The protein compositions of the HDAg-containing particles were analyzed by immunoblotting with HDAg-, HBsAg-, and hepatitis B core antigen-specific antisera and monoclonal antibodies to HBV surface gene products. The HBsAg envelope of HDAg contained approximately 95% P24/GP27s, 5% GP33/36s, and 1% P39/GP42s proteins. This protein composition was more similar to that of the 22-nm particles of HBsAg than to that of complete HBV. The significant amount of GP33/36s suggests that the HBsAg component of the HDV-associated particle carries the albumin receptor. Two proteins of 27 and 29 kilodaltons which specifically bound antibody to HDAg but not HBV-specific antibodies were detected in the interior of the 36-nm particle. Since these proteins were structural components of HDAg and were most likely coded for by HDV, they were designated P27d and P29d.

Animals↗
PubMed1985

Clinical significance of antibody to the hepatitis delta virus in symptomless HBsAg carriers.

Antibody to the hepatitis delta virus (anti-delta) was detected in 112 out of 2487 (5%) individuals fortuitously found to have the hepatitis B surface antigen (HBsAg) in the blood. Liver function was impaired in 38% (43 of 112) of the anti-delta-positive carriers but in only 9% (215 of 2375) of the anti-delta-negative subjects (p less than 0.001). Liver biopsy specimens were obtained from 31 antibody-positive and 97 antibody-negative subjects with impaired liver function. Important histological changes were observed in 61% of the 31 antibody-positive carriers (7 chronic active hepatitis, 4 active cirrhosis, 8 inactive cirrhosis) but in only 19% of the 97 antibody-negative carriers (p less than 0.001). The presence of anti-delta in serum identifies a subpopulation of apparently healthy HBsAg carriers whose risk of underlying liver disease is four times higher than that in the ordinary carrier. The identification of anti-delta in a symptom-free HBsAg carrier with abnormal liver function is thus an indication for a diagnostic liver biopsy.

Antibodies, Viral↗
PubMed1985

Risk of post-transfusion infection with the hepatitis delta virus. A multicenter study.

Hepatitis delta virus is a defective virus that can replicate only in the presence of hepatitis B virus. To determine the prevalence, circumstances of transmission, and clinical importance of infection with hepatitis delta virus, we obtained data on 262 patients with post-transfusion hepatitis who were positive for the hepatitis B surface antigen (HBsAg) even though they had received blood screened for it. We also studied 94 HBsAg carriers who were receiving repeated blood transfusions for other diseases, and 103 HBsAg carriers with hemophilia who were receiving various forms of coagulation factors. Antibody to hepatitis delta virus was found in 9 of 262 patients (3.5 per cent) with post-transfusion hepatitis, 5 of 234 (2 per cent) with self-limited disease, and 4 of 28 (14.5 per cent) with fulminant disease (P less than 0.05). The absence of IgM antibodies to the hepatitis B core antigen indicated that three of the nine patients with both HBsAg and antibodies to hepatitis delta virus had been carriers of HBsAg at the time of transfusion, and the acute disease represented the combined effects of the two viruses. Antibody to hepatitis delta virus was found in 3 of 94 Italian carriers of HBsAg who were receiving repeated blood transfusions, in none of 24 Brazilian, East German, or Australian hemophiliac carriers infused with clotting factors prepared from single or mini-pool volunteer plasma, and in 27 to 100 per cent of 79 hemophiliac carriers from European and U.S. series who received coagulation factors manufactured from large pools of plasma. We conclude that infection with hepatitis delta virus is likely to be more severe than infection with hepatitis B virus alone and that screening for HBsAg provides a high degree of safety in preventing infection with hepatitis delta virus, but that the risk is considerably greater in patients who are already carriers of HBsAg. We recommend that HBsAg carriers be given only blood derivatives prepared from a single donor or mini-pool donors.

Acute Disease↗
PubMed1985

Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe.

A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southern blot hybridization; ten carriers were negative by in situ hybridization, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellular distribution of HBV nucleic acids.

Autoradiography↗
PubMed1985

Epidemiology of hepatitis delta virus (HDV) infection.

Markers of hepatitis delta virus (HDV) infection have been detected all over the five continents. Geographical prevalence varied heavily: HDV infection is very rare in Far East Asia, but extremely frequent in Arabian countries, in Romania and in certain Indian populations of South America. In Europe and in the USA the infection is widely spread among high risk groups such as intravenous drug abusers and haemophiliacs.

Africa↗
PubMed1985

Delta hepatitis--present status.

The hepatitis delta virus (Delta) is a defective RNA pathogen dependent for replication on obligatory helper functions provided by the hepatitis B virus (HBV). The virion is a particle of 35-37 nm, which encloses within a HBsAg coat the RNA genome and the Delta antigen, the specific immunologic expression of the new pathogen. Infection is diagnosed by the presence of Delta antigen in liver and the finding of antibody to Delta in serum. The virus is infectious for primates but can also adapt to non-primates. Distribution is world-wide with peak prevalence in the Mediterranean basin, the Middle East and areas of Africa. Transmission occurs by direct parenteral inoculation and by non-parenteral routes linked to close body contacts. Delta is highly pathogenic and a cause or an aggravating factor of HBsAg-positive liver disease. Infection superimposed on acute HBV hepatitis may induce a fulminant illness. Superinfection of carriers of HBsAg may convert a previously asymptomatic carrier in a carrier with chronic hepatitis, or accelerate the downward clinical course of chronic underlying HBV disease. Carriers of HBsAg probably represent the reservoir of the virus.

Carrier State↗
PubMed1985

Infection with the delta agent in children.

Serological evidence of infection with the hepatitis B virus associated delta agent (delta) was found in 34 of 270 Italian children with HBsAg-positive liver disease. In different histological forms of chronic HBsAg hepatitis the prevalence of delta infection increased in parallel with the activity of the disease and was maximal in children with cirrhosis. During two to seven years of follow up the hepatitis deteriorated in 38% of the 34 patients with delta infection and ameliorated only in 9%. By contrast the disease usually ran a mild course in the 236 delta-negative carriers of HBsAg, with remission in 55% of these children and deterioration in only 7%. The outcome of chronic hepatitis associated with delta infection was not influenced by treatment with steroids and azathioprine. Chronic delta infection in children is usually accompanied by serious liver disease, that has a tendency to progress and is unresponsive to conventional immunosuppressive treatment.

Adolescent↗
PubMed1985

[Delta hepatitis].

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Carrier State↗
PubMed1984

Experimental infection of chimpanzees with the HBsAg-associated delta (delta) agent: an ultrastructural study.

Characteristic cytoplasmic membranous structures and intranuclear aggregates of particles similar to those reported in non-A, non-B hepatitis were observed by electron microscopy in the liver biopsies of chimpanzees inoculated with human serum, infectious for the delta agent. The ultrastructural changes were maximal during the intrahepatic production of the delta antigen, but were detected also independently of delta-Ag expression. The ultrastructural analogies provide further evidence that delta has properties distinct from HBV.

Alanine Transaminase↗
PubMed1984

Delta hepatitis agent: structural and antigenic properties of the delta-associated particle.

Delta agent (delta) was serially passaged to a second and third hepatitis B surface antigen (HBsAg) carrier chimpanzee, using as inoculum the peak delta antigen (delta Ag) serum of an animal previously infected with human serum. The characteristics of serially transmitted delta Ag were similar to those described in first-passage animals. It was consistently detected before the development of anti-delta, in association with a 35- to 37-nm subpopulation of HBsAg particles and a unique low-molecular-weight (5.5 X 10(5)) RNA. RNase susceptibility of the delta-associated RNA and release of delta Ag activity upon treatment of delta-associated particles with detergent revealed that this particle is organized into a virion-like form with the RNA and delta Ag as internal components within a coat of HBsAg. Surface determinants of the delta-associated particle other than HBsAg were not detected by radioimmunoprecipitation experiments, using sera of humans and chimpanzees convalescent from delta hepatitis. The HBsAg-associated particle is the "candidate agent" of delta hepatitis.

Animals↗