Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection

<jats:sec> <jats:title/> <jats:p> <jats:bold>The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 ± 16.3 vs. 36.0 ± 14.3 years,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>< .0017), less predominantly male (43% vs. 71%,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>= .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>< .0001), less infected with subgenotype Ae (0% vs. 13%,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>< .05), and more frequently with Bj (30% vs. 4%,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>< .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>< .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%,</jats:bold> <jats:bold> P </jats:bold> <jats:bold>= .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In</jats:bold> <jats:bold> in vitro </jats:bold> <jats:bold>transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation.</jats:bold> <jats:bold> In conclusion </jats:bold> <jats:bold>, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.</jats:bold> <jats:bold> Supplementary material for this article can be found on the HEPATOLOGY website </jats:bold> (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).</jats:p> </jats:sec>