Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis

Article Abstract:

Hepatitis B virus causes acute hepatitis in some patients and chronic liver disease in others. Still other people carry the virus without symptoms of disease. It is generally thought that the hepatitis B virus does not directly harm the liver cells it infects, and much of the damage which results from hepatitis B may result from the immune response to the virus and not from the virus itself. However, recent research has shown that in some cases of rapidly fatal hepatitis B, a peculiar viral genetic mutation may be involved. Previous research has indicated that the presence in the blood of a particular virus protein, the 'e' antigen, tends to correlate with more severe disease. The correlation is not complete, however, and some patients die of hepatitis B without the e antigen in their blood. The hepatitis B e antigen, abbreviated HBeAg, is a rather unusual protein, and its function is not known. Hepatitis B virus has a core protein which provides structural support for the viral DNA, and, naturally, the virus has a gene for this core protein. However, just before the core gene is another gene, called precore. When the protein-making process begins at the precore gene, it does not stop, but keeps right on going through the core gene. The resulting protein therefore "includes" the core protein within its structure. However, this protein is then snipped shorter at both ends; the resulting protein is HBeAg and is very similar to the core protein. To elucidate the role of HBeAg in the development of hepatitis, viral genes were sequenced from seven patients who died of severe hepatitis but without HBeAg in their blood. A mutation was found which would prematurely terminate the protein-making process in the precore region just short of the core gene. Such a mutation would prevent the synthesis of HBeAg. Since the core gene is unaffected, the virus can make plenty of core protein for the DNA of new virus particles. It is not known why the absence of the e antigen should affect the course of the disease. The observation of the same mutation in seven different patients, all of whom had either severe exacerbations of chronic hepatitis B or explosively rapid fatal hepatitis B, suggests that the mutation is likely to play an important role. (Consumer Summary produced by Reliance Medical Information, Inc.)

---

Variants of hepatitis B virus associated with fulminant liver disease

Article Abstract:

In the June 13, 1991 issue of The New England Journal of Medicine, two separate research groups present findings which demonstrate that a specific mutation in the hepatitis B virus can result in a particularly severe and fatal form of the liver disease. Curiously, the mutation affects a viral protein whose function is not known. The 'e' antigen of the hepatitis B virus, abbreviated HBeAg, is often correlated with increasing severity of disease. However, the rule is far from hard and fast, since patients may have HBeAg in their blood without symptoms of disease, and patients may suffer a fulminant, or rapidly fatal, hepatitis with no detectable HBeAg. The e antigen is related to the core protein of the viral particle itself. However, unlike the core protein, which is a fundamental part of the viral structure, the function of the e antigen is not known. As infected cells are manufacturing more virus particles, the gene for the e antigen is transcribed and translated into a protein molecule; this molecule actually includes the structure of the core protein. However, the e antigen is then cleaved at both ends, and the resulting protein is, in fact, smaller than the core protein. The researchers demonstrated that in some patients who died of fulminant hepatitis B, a mutation could be found which prematurely terminates the genetic transcription process before the molecular machinery gets as far as the core protein gene. As a result, no detectable e antigen is synthesized. While it is certain that this viral mutation can cause especially severe hepatitis B, it is also clear that individuals may be infected with this same mutant virus without developing severe hepatitis. The elegant genetic research presented in this issue of the Journal provides important new insights into the nature of the hepatitis B virus. However, the results also suggest that hepatitis B itself cannot be understood without learning more about the individual immunological response of each patient to this viral infection. (Consumer Summary produced by Reliance Medical Information, Inc.)

Causes of, editorial

---

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

Article Abstract:

There is evidence that a mutation affecting the hepatitis B e antigen, or HBeAg, may be involved in particularly severe cases of hepatitis B, a type of liver infection. However, while mutation rates are low, so many viruses may be produced so rapidly during an infection that the occurrence of a mutation becomes likely just by chance. Therefore, when a mutant virus is discovered in an infected individual, it becomes important to ask whether the patient was infected with a mutant virus or whether the mutation was a chance occurrence in the patient's body which followed the initial infection by a standard "wild type" virus. An outbreak of fulminant hepatitis B in a hospital provided an opportunity to answer this question. (Fulminant hepatitis B is a form of the liver infection that progresses especially rapidly.) The source of the outbreak of hepatitis B was traced to a single patient who had been hospitalized for gastrointestinal bleeding related to advanced liver disease. Five other patients in the hospital contracted rapidly fatal hepatitis B. A genetic analysis of the hepatitis B virus specimens obtained from these patients revealed the same genetic mutation in every case, including the patient who was the source of the infection. This finding demonstrates that the mutation was present in the virus which initially infected the five patients with fatal fulminant hepatitis and was not merely the result of a mutation which occurred during the progress of the infection. The function of HBeAg is not known, nor is it understood why the absence of this protein should result in such a particularly severe hepatitis. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prognosis

Similar abstracts:

• Abstracts: A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan. Role of hepatitis C virus in non-B chronic liver disease
• Abstracts: Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas
• Abstracts: High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection
• Abstracts: Home monitoring of transcutaneous oxygen tension in the early detection of hypoxaemia in infants and young children
• Abstracts: Long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Natural history of opportunistic disease in an HIV-infected urban clinical cohort

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.