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Initial load of hepatitis B virus (HBV), its changing profile, and precore/core promoter mutations correlate with the severity and outcome of acute HBV infection

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Abstract

Background

The pathogenesis of the fulminant or severe form of acute hepatitis B virus (HBV) infection remains unclear, although both host- and virus-specific factors are considered to have a great impact on the c course. We aimed to define possible viral factors implicated in the severe form of acute HBV infection.

Methods

We investigated viral factors in 42 patients with acute HBV infection: 11 had fulminant hepatitis (FH); 9 had a severe form of acute hepatitis (SAH), defined as having a prothrombin activity of less than 40% without encephalopathy; and 22 had acute self-limited hepatitis (AH).

Results

Although there was no significant difference in serum HBV DNA levels on admission among the three groups, the level decreased more rapidly in patients with SAH or FH than in those with AH. In patients with SAH or FH, the HBV load on admission was higher in patients who died than in those who recovered (7.0 ± 1.6 vs 5.6 ± 1.0 log copies/ml; P = 0.0293). In univariate analysis, seronegativity for hepatitis B envelope antigen (HBeAg) and mutations in both the precore (G1896A and/or G1899A) and core promoter (T1753A/C and/or T1754C/G and/or A1762T/G1764A) were associated with FH (odds ratio [OR], 5.60; P = 0.0269 and OR, 52.0; P = 0.0006; respectively). In multivariate logistic regression analysis, only the presence of precore/core promoter mutations was associated with FH (OR, 42.8; P = 0.0020).

Conclusions

The rapid decrease in viral load in the early phase of acute HBV infection was associated with the severity of the disease. A high viral load on admission and the presence of both precore and core promoter mutations in patients with severe coagulopathy closely correlated with mortality.

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Author notes

  1. Shigehiko Sainokami

    Present address: Department of Internal Medicine, Fussa Hospital, 1-6-1 Kamidaira, Fussa, Tokyo, 197-8511, Japan

Authors and Affiliations

  1. First Department of Internal Medicine, Iwate Medical University, Iwate, Japan

    Shigehiko Sainokami, Koichi Abe, Akihiro Sato, Ryujin Endo, Yasuhiro Takikawa & Kazuyuki Suzuki

  2. Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan

    Hiroaki Okamoto

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  1. Shigehiko Sainokami
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Sainokami, S., Abe, K., Sato, A. et al. Initial load of hepatitis B virus (HBV), its changing profile, and precore/core promoter mutations correlate with the severity and outcome of acute HBV infection. J Gastroenterol 42, 241–249 (2007). https://doi.org/10.1007/s00535-006-1997-5

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