B型肝炎病毒基因體變異在慢性B型肝炎急性發作的角色探討: 一前瞻性全長病毒基因體研究
Date Issued
2003
Date
2003
Author(s)
劉俊人
DOI
912314B002402
Abstract
The onset of acute exacerbation (AE) during the course of chronic hepatitis B is likely related
to the break of balance between virus and host immune responses. Whether such a break of immune
tolerance is triggered major by the changes of host immune status or by an alteration of HBV
hepatitis B virus (HBV) genome still remains controversial. To address this issue, a prospective
study from silent (asymptomatic) stage to acute exacerbation and a full-length sequencing strategy
are needed.
Although the underlying mechanism remains unknown, clinical observations and animal
studies clearly show that an upsurge of viral load always precedes or sometimes coincides with AE
in chronic hepatitis B. Thereby, a key to the understanding of these AEs seems to unravel the origin
and identity of such a viral surge. To clarify these issues, in the first year, we have already
collected the clinical and serological data from 14 patients who developed acute exacerbation of
chronic hepatitis B spontaneously, after discontinuing lamivudine treatment, or during interferon
treatment. We first regularly monitored the serum ALT levels and HBV DNA levels during the
development of acute exacerbation. Our results consistently showed that serum viral load resurged
before the maximal hepatitis activity in 13 (93%). We then performed full-length HBV genome
sequencing from the serum samples obtained at 4 points: at enrollment, at the peak of serum viral
load, at the peak of serum ALT level, and after acute exacerbation. We found that the viral genome
at virologic peak remained almost identical to that at baseline in 12 (86%) of them. On the contrary,
the viral genomes obtained after the development of hepatitis exacerbation are different from the
corresponding one at baseline in 7 (50%).
Our preliminary results suggested that the development of hepatitis B exacerbation was not
related to the changes of HBV genome. Nevertheless, from a viral evolution point of view, we need
to consider the origin of the HBV strains at baseline. Some viral strains may exist and remain
inactive in the host for a long time before reactivation, as is the case of chemotherapy-induced AE.
The other baseline viral strains, especially those from repeated spontaneous AE, may just represent
survivors from previous episode of AE. These HBV survivors may either be new viral variants
selected out from host immune surveillance in previous exacerbation, or they may remain the same
strain as prior to preceding AE and again trigger the current episode of exacerbation.
In the second year, the sequential serum dominant viral sequences in some individuals with
several episodes of AE will be determined to clarify if the viral variant selected during first AE will
trigger a new AE. The in vitro phenotype of the viral variants emerged during AE will be
determined. The representation of the serum viral genome to the intra-hepatic one will be
determined by comparing the dominant viral sequences in the serum and liver specimens obtained
simultaneously from the same individuals. Finally, the serial serum cytokines such as TNF-α and
IFN-γ will be determined to see if antiviral host factors become defective before AE.
We expect providing evidence to clarify whether alteration of viral genome besides host factor
is related to the trigger of AE. In longitudinal follow-up, we can further clarify the impact of viral
variations on AE and the biologic behavior of the emerged viral variants.
Subjects
Acute exacerbation
hepatitis B virus
variant
viral load
full-length
genome
prospective
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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