Universal Emergence of Precore Mutant Hepatitis B Virus along with Seroconversion to Anti-HBe Irrespective of Subsequent Activity of Chronic Hepatitis B

Abstract

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.

Current status of liver diseases in Korea: Hepatitis B

“…Some investigators suggested the emergence of precore mutant HBV as a universal phenomenon during the natural history of chronic HBV infection and that the precore mutant did not appear to have pathogenic role. 42 In contrast, other investigators proposed the clinically important role of mutations in the progression of HBV-related liver diseases because BCP and precore mutations were more frequent in advanced liver diseases than in the other clinical statuses. 43 Pre-S mutations were also detected in advanced liver diseases, and were considered to have a clinical significance.…”

Hepatitis B in childhood: An update for the paediatrician

“…Rarely, seroconversion may result from the development of a 'precore mutant' (whereby a mutation occurs at nucleotide 1896 in the precore region of the HBV DNA genome). This mutation of uncertain virulence occurs during the course of infection and renders the virus incapable of producing HBeAg (8).…”

A novel primer‐extension assay for the detection of a G to A mutation in the distal precore region of hepatitis B virus DNA

“…The mutation occurs at nucleotide (nt) 1896 where a guanine (G) to adenine (A) change results in a TAG stop codon at codon 28 of the precore region that interferes with the synthesis of HBeAg [5,8,9]. However, subsequent studies have failed to prove any consistent relationship between the precore stop codon mutation and the severity of the liver disease [8,[10][11][12]. More recently, mutations of the core gene and the core promoter gene have been investigated and many studies have reported that core gene or core promoter gene mutations are more closely associated with severity of HBV infection and responsiveness to interferon-α treatment than the precore stop codon mutation [13][14][15][16][17].…”