A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis

N Engl J Med. 1991 Jun 13;324(24):1705-9. doi: 10.1056/NEJM199106133242405.


Background: A nosocomial outbreak of fulminant hepatitis B occurred in five patients in Haifa, Israel. Previous investigations identified the suspected source as a carrier of hepatitis B surface antigen who was positive for antibodies to hepatitis B e antigen and had chronic liver disease. We examined the strain of hepatitis B virus (HBV) that caused this epidemic, in order to identify specific mutations in the precore or core region.

Methods: The presence of HBV was identified by polymerase-chain-reaction amplification of viral DNA in serum from the source patient, the five patients with fulminant hepatitis B, and five controls with acute, self-limited hepatitis B. The amplified viral HBV DNA samples were then cloned and sequenced.

Results: Sequence analysis of viral DNA established that the same HBV mutant with two mutations in the precore region was present in the source patient and the five patients with fulminant hepatic failure. This HBV mutant had significant sequence divergence from other known HBV subtypes in the X, precore, and core regions. Cloned HBV DNA derived from a hospitalized patient who had subclinical hepatitis B at the same time as the outbreak and from four other control subjects with acute, self-limited hepatitis B all contained the wild-type sequence in the precore region.

Conclusions: In the outbreak we studied, a mutant hepatitis B viral strain was transmitted from a common source to five patients who subsequently died of fulminant hepatitis B infection. Naturally occurring viral mutations hepatitis B infection. Naturally occurring viral mutations in the HBV genome may predispose the infected host to more severe liver injury.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carrier State / immunology
  • DNA, Viral / analysis
  • Disease Outbreaks / statistics & numerical data
  • Hepatitis B / epidemiology
  • Hepatitis B / microbiology*
  • Hepatitis B Antibodies / analysis
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / genetics*
  • Humans
  • Israel / epidemiology
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction


  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens