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

Abstract

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, P < .0017), less predominantly male (43% vs. 71%, P ‫؍‬ .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .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%, P < .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%, P ‫؍‬ .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 in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, 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.

Role of TNF-α Produced by Nonantigen-Specific Cells in a Fulminant Hepatitis Mouse Model

“…It was reported that the intracellular accumulation of HBV DNA and Ags may play a role in inducing liver damage (20). Moreover, HBV/ genotype Bj was an independent risk factor for the development of fulminant hepatitis, and the expression of intracellular Ags in HBV/genotype Bj was the highest (20,21). Therefore, the HBsAg transgenic mouse lineage 107-5D may be suitable for the analysis of human fulminant hepatitis because the HBsAg particles were retained within the endoplasmic reticulum of the hepatocyte in this lineage.…”

Genetic Diversity of HBV Genotypes/ Subgenotypes and Their Correlation with Disease Progression

“…158 In Japan, persistence of HBV was associated with Ae, whereas fulminant hepatitis was associated with Bj. 161 In a study from Vietnam, genotype A was more frequent in asymptomatic patients as compared with symptomatic patients. Genotype C was more frequent in patients with HCC.…”

Strategy for preventing hepatitis B reactivation in patients with resolved hepatitis B virus infection after rituximab-containing chemotherapy

“…2,3 The researchers should specify whether the kinetics of HBV DNA and severe hepatitis were associated with precore and/or basal core promoter mutations in the patients with HBV reactivation, because general readers need to be aware of such important viral factors to perform safe monitoring of HBV DNA.…”