ObjectivesIt has been controversial whether or not the emergence of precore mutant HBV is related to the severe form of chronic hepatitis B (CH-B). To further clarify the role of the precore mutant HBV in the natural course of CH-B, we conducted a longitudinal analysis of precore-region sequences according to the biochemical severity along with seroconversion to anti-HBe in patients with CH-B.MethodsThe precore sequences of the ten sets of serial serum samples, obtained from 6 chronic hepatitis B patients with (group I) and from 4 patients without subsequent biochemical remission after seroconversion to anti-HBe (group II), were analyzed by direct sequencing of DNA amplified by PCR.ResultsThe precore mutat HBV having a G-A mutation at the nucleotide 1896 was most commonly found (9/10). Wild-type precore HBV was detected in 4 of 6 (66.7%) in group I and 3 of 4 (75.0%) in group II during HBeAg-positive period (p >0.05), and during anti-HBe-positive period it was found in 2 of 6 (33.3%) in group I and 0 of 4 (0%) in group II (p >0.05). In contrast, precore mutant HBV was detected in 5 of 6 (83.3%) in group I and 2 of 4 (50.0%) in group II during HBeAg-positive period (p >0.05), and in all patients of both groups during anti-HBe-positive period.ConclusionThe most common type of precore mutant HBV in Korea was the mutant with a G-A mutation at nucleotide 1896. The emergence of precore mutant HBV was a universal phenomenon during the natural history of CH-B; therefore, the precore mutant does not appear to have an pathogenic role in determining the severity of the CH-B.
Objectives:There are regions in the core gene of hepatitis B virus (HBV) where missense mutations are clustered, and mutations in that region are related to severe liver disease. However, there were some differences of the major regions for mutation clustering among ethnic groups. To explore the phenomenon of clustering mutations in Korean patients with chronic HBV infection and to elucidate the correlation between clustering mutation region of the core gene and the severity of liver damage, we analyzed the precore/core gene sequence of HBV in the sera from fifteen chronic hepatitis B (CH-B) patients.Methods:We analysed the HBV precore and core sequences in the sera obtained from fifteen patients (14 males and 1 female, mean age 30.0 years) with biopsy-proven CH-B. The patients were divided into two groups according to the pathological severity of CH-B; namely, group I consisted of 8 patients with chronic persistent hepatitis (CPH), and group II included 7 patients with chronic active hepatitis (CAH). After extraction of HBV DNA from each serum by proteinase K and phenol-chloroform solution, the entire precore and core region of HBV was amplified by PCR, and then the PCR products were subjected to direct sequencing using thermostable DNA polymerase. Fisher’s exact test and Mann-Whitney U test were used for statistical analysis.Results:A total of 181 nucleotide substitutions were found in the HBV core gene from the 15 CH-B patients, of which 23 were missense and 158 were silent. The nucleotide and amino acid substitution rates were not significantly different between the two groups (p>0.05). Two mutational hot spots (MHS), codons 21–34 (MHS1) and codons 85–100 (MHS2), were found in the deduced amino acid alignment of the core gene. The alteration rate of amino acid residue in these regions were 2.857×10−2 and 5.000×10−2, respectively. Of 8 CPH patients, 5 showed missense mutations only in MHS2. In comparison, of 7 CAH patients, 3 showed them both in MHS1 and MHS2, 1 only in MHS1, and 1 only in MHS2; thus, missense mutation in MHS1 was exclusively found in patient with CAH.Conclusions:There were two mutation clusterings in the core region of adr subtype of HBV from Korean CH-B patients. Mutations in MHS1 (codon 21–34), but not in MHS2 (codon 85–100), are more likely to be related to the severity of CH-B. A longitudinal study using sequential samples is warranted to further clarify the role of MHS1 in the pathogenesis of more severe CH-B.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.