Dataset Information

Sequence analysis of the Pre-S gene in chronic asymptomatic HBV carriers with low-level HBsAg.

ABSTRACT: In a hepatitis B virus (HBV)?infected population, persistently low expression levels of serum HBV serum antigen (HBsAg) are present, particularly in chronic asymptomatic HBV carriers (ASCs). The present study sequenced the HBV Pre?S gene, and aimed to elucidate its features in ASCs with low HBsAg expression compared with in the established HBV Pre?S reference gene sequences from ASCs with high HBsAg expression. A total of 1,308 ASCs were grouped according to HBsAg serum levels (cut?off value, 10 IU/ml), and clinical characteristics were analyzed in detail. The HBV Pre?S gene was sequenced in 276 ASCs with low?level HBsAg; in addition, 100 of the remaining 1,032 ASCs with high?level HBsAg were randomly selected for HBV Pre?S gene sequencing on the basis of age matching with the low?level HBsAg group. Comparative analysis of the gene sequences from these groups was subsequently conducted. The major clinical features of the population with low?level HBsAg were as follows: Most were ASCs with chronic HBV infection; 97.1% were HBsAg/anti?HBe/anti?HBc?positive; 82.54% carried the B genotype; and 84.13% displayed the adw serotype. The results indicated that there were novel and meaningful mutations, including co?mutations, at numerous loci and sites in the Pre?S gene, as well as deletion mutations in the Pre?S2 gene. These mutations in the Pre?S1 and Pre?S2 gene fragments accounted for 65.38% (68/104) of the 104 B genotype cases in the low?level HBsAg group and 90.91% (20/22) of the 22 C genotype cases in the low?level HBsAg group, respectively. In conclusion, Pre?S gene mutations may be associated with HBV replication defects, which may be the cause of the observed low expression levels of HBsAg.

SUBMITTER: Wang T

PROVIDER: S-EPMC6192773 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Sequence analysis of the Pre-S gene in chronic asymptomatic HBV carriers with low-level HBsAg.

Wang Tong T Dai Yuzhu Y Zhang Meng M Cui Dawei D Xu Xujian X Sun Changgui C Cheng Jun J

International journal of molecular medicine 20180817 5

In a hepatitis B virus (HBV)‑infected population, persistently low expression levels of serum HBV serum antigen (HBsAg) are present, particularly in chronic asymptomatic HBV carriers (ASCs). The present study sequenced the HBV Pre‑S gene, and aimed to elucidate its features in ASCs with low HBsAg expression compared with in the established HBV Pre‑S reference gene sequences from ASCs with high HBsAg expression. A total of 1,308 ASCs were grouped according to HBsAg serum levels (cut‑off value, 10 ...[more]

PMID: 30132518

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Project description:Background & aimsHBsAg proteins are useful to identify HBV inactive carriers (ICs), but data on chronic hepatitis D (CHD) are scarce. This study aimed to describe HBsAg composition in CHD, its changes during the evolution, and the potential association with clinical outcomes. In addition, we assess the composition of HBsAg across different HBV genotypes and validate previous results on HBsAg proteins in an independent HBV cohort.MethodsQuantitative HBsAg, medium HBsAg proteins (MHBs), and large HBsAg proteins (LHBs) were measured in two cohorts. The first cohort consisted of patients with CHD. A cross-sectional study of samples from two European institutions (N = 46) was conducted. Outcomes were assessed in a retrospective-prospective study of those patients with a follow-up of >1 year (n = 36), and the longitudinal evolution of HBsAg proteins in those with samples >5 years apart (n = 12) was analysed. The second cohort consisted of patients with HBeAg-negative HBV, and a cross-sectional study was performed (N = 141).ResultsForty-one (89%) patients with CHD had detectable HDV-RNA, and the presence of HDV-RNA was associated with higher LHBs proportion (p = 0.010). Baseline MHBs (p = 0.051) and MHBs proportion (p = 0.086) tended to be higher in those developing clinical outcomes (9/36, 25%) after a median follow-up of 5.9 years. Patients in which HDV-RNA became spontaneously undetectable during follow-up (5/31, 16.1%) tended to present lower MHBs proportion (p = 0.085). In the longitudinal study, changes in LHBs proportion were observed (p = 0.041), whereas MHBs proportion remained stable (p = 0.209). Regarding HBV, ICs showed lower LHBs proportion (p = 0.027). LHBs and MHBs differed significantly according to HBV genotype, regardless of the HBV phase.ConclusionsPatients with CHD with detectable HDV-RNA presented higher LHBs proportion than those with undetectable HDV-RNA. A trend toward having higher baseline MHBs proportion was observed in patients who developed clinical outcomes or remained with detectable HDV-RNA. This study validates the different HBsAg composition in HBV ICs and reveals the HBV-genotype influence in HBsAg composition.Impact and implicationsThe composition of HBsAg in chronic hepatitis D differs in patients with detectable and undetectable HDV viral load and may help predict the likelihood of achieving undetectable HDV viraemia and the development of clinical events such as decompensation. The composition of the surface antigen is also useful to distinguish inactive carriers of HBV, and it varies according to HBV genotype.

Project description:Certain patients with hepatitis B virus (HBV) infection present with persistently low levels of serum hepatitis B surface antigen (HBsAg) and have been indicated to have low rates of HBV nucleic acid replication. To explore the serological and molecular epidemiological characteristics of HBV population with low-level HBsAg in the present study, associated serum markers and virologic genotype detection were performed accordingly. Determination of HBV markers was performed using a chemiluminescence immunoassay from which 2,544 out of 45,256 adults who underwent routine health examination were tested positive for HBsAg. HBV DNA was detected by real-time fluorescent quantitative PCR. The patients were divided into low-level and high-level groups, according to their HBsAg levels (cut-off value, 10 IU/ml). The prevalence and levels of HBsAg positivity and HBV DNA in patients with HBV infection were analyzed by age, sex, serological pattern and clinical type. The fibrosis status of patients with low-level HBsAg was assessed by determining the aspartate aminotransferase-to-platelet ratio (APRI), and sequencing was employed to determine serotypes and genotypes. HBV-infected patients with low-level HBsAg (<10 IU/ml) accounted for 15.41% of the 2,544 HBsAg-positive patients, and the prevalence of HBsAg positivity exhibited a tendency to increase with age. The male-to-female ratio was ~1.9:1, and the average age was 54.98±16.28 years among HBV-infected patients with low-level HBsAg. The major serological pattern and clinical types were HBsAg/antibody against hepatitis Be antigen (anti-HBe)/antibody against hepatitis B core antigen (anti-HBc)-positive (94.90%) and chronic asymptomatic (ASC) (97.95%), respectively. HBV DNA exhibited a low-level of replication and the prevalence of HBV DNA positivity assessed by the routine method and by the enrichment method was 27.74% (97/392) and 45.92% (180/392), respectively. No significant differences among the age groups were identified in the different HBsAg level groups (P>0.05). The prevalence of HBV DNA positivity was associated with HBsAg only in patients with serological pattern HBV-M2 (HBsAg/anti-HBe/anti-HBc-positive) in the low-level HBsAg group (odds ratio: 1.30; 95% CI: 1.15-1.47; P<0.05). The APRI had no association with age, HBsAg, HBV DNA level or liver function index in ASC patients in the low-level HBsAg group (P>0.05). The prevalence of the serotype adw and genotype B was 85.53 and 89.47%, respectively. Further improvement in the systematic study of populations with low-level HBsAg has important clinical and epidemiological significance for improving the detection of HBV serological markers, elucidating the mechanisms leading to low-level HBsAg, overcoming immune tolerance to eliminate HBV infection and preventing HBV transmission.

Dataset Information

Sequence analysis of the Pre-S gene in chronic asymptomatic HBV carriers with low-level HBsAg.

Publications

Sequence analysis of the Pre-S gene in chronic asymptomatic HBV carriers with low-level HBsAg.

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