INFLUENCE OF DELTA INFECTION ON SEVERITY OF HEPATITIS B

doi:10.1016/S0140-6736(82)90156-8

The Lancet

Volume 320, Issue 8305, 30 October 1982, Pages 945-947

https://doi.org/10.1016/S0140-6736(82)90156-8 Get rights and content

Abstract

The prevalence of serum markers of primary delta infection was determined in 532 patients with acute benign hepatitis B seen in Italy, and in 111 patients with fulminant hepatitis B seen in Italy, France, and England. Patients with fulminant hepatitis had a significantly higher prevalence of delta markers (43/111, 39%) than did those with benign hepatitis (101/532, 19%). In 25 of the 43 patients with delta-positive fulminant hepatitis, serum markers indicated a primary hepatitis B infection while in the remaining 18, IgM antibody to hepatitis B core antigen was absent, indicating that hepatitis B preceded superinfection with the delta agent. The increased morbidity of HBsAg hepatitis with delta infection may result from the cumulative simultaneous exposure to hepatitis B virus and delta, or from superinfection of HBsAg carriers with delta.

References (22)

M. Rizzetto et al.
Incidence and significance of antibodies to delta antigen in hepatitis B virus infection
Lancet
(1979)
A. Smedile et al.
Infection with the HBV associated delta (δ) agent in HBsAg carriers
Gastroenterology
(1981)
M. Rizzetto et al.
Transmission of hepatitis B virus-associated delta antigen to chimpanzees
J Infect Dis
(1980)
M. Rizzetto et al.
Delta antigen: the association of delta antigen with hepatitis B surface antigen and ribonucleic acid in the serum of delta infected chimpanzees
Proc Natl Acad Sci USA
(1980)
M. Rizzetto
Biology and characterization of the delta agent
Jl Germ et al.
Serial passage of the delta agent (δ) in chimpanzees
Fed Proc
(1982)
M. Rizzetto et al.
Immunofluorescence detection of a new antigen-antibody system (δ/anti-δ) associated with the hepatitis B virus in the liver and in the serum ofHBsAg carriers
Gut
(1977)
E. Stoecklin et al.
Delta antigen in hepatitis B: Immunohistology of frozen and paraffin-embedded liver biopsies and relation to HBV-infection
Hepatology
(1981)
A. Picciotto et al.
Interplay of cell and serum immunologic markers in chronic persistent or active hepatitis B
J Med Virol
(1981)
F. Bonino et al.
The δ agent: HBsAg particles with δ antigen and RNA in the serum of an HBV carrier
Hepatology
(1981)

There are more references available in the full text version of this article.

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INFLUENCE OF DELTA INFECTION ON SEVERITY OF HEPATITIS B

Abstract

Lancet

Gastroenterology

Transmission of hepatitis B virus-associated delta antigen to chimpanzees

J Infect Dis

Delta antigen: the association of delta antigen with hepatitis B surface antigen and ribonucleic acid in the serum of delta infected chimpanzees

Proc Natl Acad Sci USA

Biology and characterization of the delta agent

Serial passage of the delta agent (δ) in chimpanzees

Fed Proc

Immunofluorescence detection of a new antigen-antibody system (δ/anti-δ) associated with the hepatitis B virus in the liver and in the serum ofHBsAg carriers

Gut

Delta antigen in hepatitis B: Immunohistology of frozen and paraffin-embedded liver biopsies and relation to HBV-infection

Hepatology

Interplay of cell and serum immunologic markers in chronic persistent or active hepatitis B

J Med Virol

The δ agent: HBsAg particles with δ antigen and RNA in the serum of an HBV carrier

Hepatology