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Nucleotide sequence analysis of the precore region in patients with spontaneous reactivation of chronic hepatitis B
Insights
Precore mutations in Hepatitis B virus (HBV) can influence chronic hepatitis B (CHB) reactivation. Some HBeAg-positive patients developed these mutations during reactivation, while HBeAg-negative patients often had them prior, potentially indicating attenuated viral replication.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- The role of HBV precore mutations in spontaneous chronic hepatitis B (CHB) reactivation is not well understood.
- Hepatitis B virus (HBV) infection can lead to chronic liver inflammation and reactivation.
Purpose of the Study:
- To investigate the association between HBV precore mutations and spontaneous reactivation in patients with CHB.
- To analyze sequence variations in the precore and core regions of HBV during reactivation events.
Main Methods:
- Studied 10 CHB patients undergoing spontaneous reactivation (5 HBeAg+ and 5 anti-HBe+).
- Sequenced precore (87 nt) and proximal core (81 nt) regions of HBV from serum samples collected before, during, and after reactivation.
- Utilized PCR amplification for viral DNA detection.
Main Results:
- In HBeAg+ patients, 2/5 developed HBeAg-defective mutations (G to A at nt 1896) during reactivation.
- In anti-HBe+ patients, 3/5 harbored HBeAg-defective mutants before and during reactivation; 2/3 became HBV DNA negative post-reactivation.
- Observed other sequence polymorphisms, some altering amino acid sequences, present initially or developing during reactivation.
Conclusions:
- Spontaneous CHB reactivation in HBeAg+ patients can be accompanied by a shift towards HBeAg-defective mutants.
- HBeAg-defective HBV mutations are frequently present before reactivation in anti-HBe+ patients.
- Pre-existing precore defective mutants may precede an attenuation of viral replication during spontaneous reactivation.
Abstract:
The role of HBV precore mutations in the spontaneous reactivation of chronic hepatitis B (CHB) is currently unknown. We studied 10 patients with CHB; five were HBeAg+ (group I) and five were anti-HBe+ (group II). All 10 had spontaneous reactivation of CHB as defined by the appearance of clinical symptoms along with an increase of serum ALT activity at least 5X above baseline values, in the absence of any other known causes of liver disease or CHB reactivation. The precore (87 nt) and proximal core (81 nt) regions were sequenced after PCR amplification. From each patient three serum samples studied: one 3-12 months before, one during, and one six months after reactivation. Prior to reactivation, none of the group I patients harbored an HBV strain having a mutation that prevented HBeAg synthesis; however, 2/5 developed such a mutation during reactivation (G to A transition at nt 1896). Among the group II patients, three harbored an HBeAg defective mutant both before and during reactivation; after six months, two of these three patients were HBV DNA negative in serum by PCR. Several other sequence polymorphisms, some of which changed the predicted amino acid sequence, were either present initially or developed during reactivation. In conclusion, in this small group of CHB patients who were HBeAg+ spontaneous reactivation was accompanied in some cases by a shift to an HBeAg defective mutant, while in patients who were anti-HBe+, such mutations were frequently present prior to reactivation. In patients already harboring precore defective mutants, spontaneous reactivation may precede an attenuation of viral replication.