title: Hepatitis B virus heterogeneity, one of many factors influencing the severity of hepatitis B.
abstract: The pathogenesis of hepatitis B can be subdivided into three sequentially correlated events: (a) loss of virus tolerance, (b) liver cell necrosis mediated by virus specific inflammatory response, (c) non-specific death of functionally compromised hepatocytes mediated by inflammatory cytochines released by virus specific inflammatory response. The severity of liver damage depends on the occurrence of these events as well as other factors. The HBeAg defective mutant appears to be involved in the loss of virus tolerance and therefore in the pathogenesis of acute hepatitis B. In addition it is positively selected by antiviral immunoreaction, behaves as an escape mutant, and it also contributes to the pathogenesis of chronic hepatitis B. The combination of these characteristics explains the relative prevalence of this mutant over wild-type HBV in patients with severe acute hepatitis B and in chronic HBsAg carriers during anti-HBe seroconversion and/or hepatitis B exacerbations. However, the absence of HBeAg defective mutants in some cases of severe and fulminant hepatitis B as well as its detection in asymptomatic carriers of HBsAg should not be surprising. The severity of hepatitis is influenced by many other factors: the number of virus infected cells, the competence and genetic heterogeneity of the immune system, the vigor and extent of non-specific inflammatory response and the killing of hepatocytes endangered by other diseases or infected with other hepatotropic viruses.
authors.affiliation: Department of Gastroenterology, Molinette Hospital, Torino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bonino
authors.forename: M R
authors.initials: MR
authors.lastname: Brunetto
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D006509:Hepatitis B / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D009336:Necrosis