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G1896A Precore Mutation and Association With HBeAg Status, Genotype and Clinical Status in Patients With Chronic Hepatitis B.

ABSTRACT: BACKGROUND:Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia. OBJECTIVES:We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate. PATIENTS AND METHODS:Serum samples from 93 patients confirmed as hepatitis B carriers were collected for molecular assay. The whole genome of HBV was amplified by polymerase chain reaction and directly sequenced. The precore and basal core promoter regions were analyzed for presence of mutations. RESULTS:The most commonly observed mutation in the precore region was C1858T with 64.5% prevalence. The precore mutation of interest (G1896A) was identified in 25.8% of isolates. The basal core promoter mutations detected were A1762T-G1764A (26.9%), C1653T (8.6%), A1752G (10.8%) and C1766T (2.2%). No significant association was observed between G1896A mutation and HBeAg-negativity. Nonetheless, G1896A was highly prevalent among HBV genotype B. Clinical association revealed that subjects with G1896A mutations were mainly detected in asymptomatic chronic hepatitis B (58.3%) and liver cirrhosis (41.7%). One subject was diagnosed with fulminant hepatitis (4.2%) and 8.3% had hepatocellular carcinoma (HCC). CONCLUSIONS:Our data suggested an intermediate prevalence of G1896A mutation among Malaysian hepatitis B carriers. The stop codon mutation has a significant association with genotype B and patients with chronic hepatitis B and liver cirrhosis.

SUBMITTER: Suppiah J

PROVIDER: S-EPMC4644636 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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G1896A Precore Mutation and Association With HBeAg Status, Genotype and Clinical Status in Patients With Chronic Hepatitis B.

Suppiah Jeyanthi J Mohd Zain Rozainanee R Bahari Norazlah N Haji Nawi Salbiah S Saat Zainah Z

Hepatitis monthly 20151028 10

<h4>Background</h4>Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia.<h4>Objectives</h4>We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate.<h4>Patients and methods</h4>Serum samples from 93 patients confirmed as hepat ...[more]

PMID: 26587040

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Project description:AimIn order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections).ResultsOverall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896.DiscussionHBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.

Dataset Information

G1896A Precore Mutation and Association With HBeAg Status, Genotype and Clinical Status in Patients With Chronic Hepatitis B.

Publications

G1896A Precore Mutation and Association With HBeAg Status, Genotype and Clinical Status in Patients With Chronic Hepatitis B.

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