Case Report: Application of hepatitis B virus (HBV) deep sequencing to distinguish between acute and chronic infection

Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral diversity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR). The distinction between these two scenarios may be important in predicting prognosis and underpinning treatment decisions, but can be challenging based on routine laboratory tests. Through application of deep whole-genome sequencing we typed the isolate as genotype-D1, and identified several minority variants including G1764A and G1986A substitutions in the pre-core promoter and pre-core regions, which support CHB-AR rather than AHB. In the longer term, enhanced deep sequencing data for HBV may provide improved evidence to distinguish between acute and chronic infection, to predict outcomes and to stratify treatment.

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Deep sequencing of hepatitis B virus basal core promoter and precore mutants in HBeAg-positive chronic hepatitis B patients

Scientific Reports ◽

10.1038/srep17950 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 12

Author(s):

Linlin Yan ◽

Henghui Zhang ◽

Hui Ma ◽

Di Liu ◽

Wei Li ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Deep Sequencing ◽

Core Promoter ◽

Basal Core Promoter ◽

B Virus ◽

Positive Chronic Hepatitis

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Effects of Hepatitis B Virus Mutations on its Replication and Liver Disease Severity

The Open Virology Journal ◽

10.2174/1874357901307010012 ◽

2013 ◽

Vol 7 (1) ◽

pp. 12-18 ◽

Cited By ~ 11

Author(s):

Abdulrahim Hakami ◽

Abdelwahid Ali ◽

Ahmed Hakami

Keyword(s):

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Disease Severity ◽

Chronic Infection ◽

Core Promoter ◽

Basal Core Promoter ◽

Double Mutation ◽

B Virus ◽

Genotype C

Hepatitis B virus (HBV), nowadays, is one of the major human pathogens worldwide. Approximately, 400 million people worldwide have chronic HBV infection. Only 5% of persons infected during adulthood develop chronic infection. The reverse is true for those infected at birth or in early childhood, i.e. more than 90% of these persons progress to chronic infection. Currently, eight different genotypes o f HBV have been identified, differing in nucleotide sequence by greater than 8%. In addition, numerous subgenotypes have a l s o been recognized based on the nucleotide sequence variability of 4- 8%. It has invariably been found that these genotypes and mutations play a pivotal role in the liver disease aggravation and virus replication. The precore mutations (G1896A) and the double mutation (T1762/A1764) in the basal core promoter are important mutations that alter expression of the hepatitis B e antigen (HBeAg). The HBeAg is important for establishing viral persistence. The precore G1896A mutation abrogates the expression of HBeAg. Numerous other mutations alter the disease severity and progression. It is predictive that the infected patient has high risk of hepatocellular carcinoma if the genotype C is incriminated or if HBV possesses basal core promoter double mutation. Association of the remaining genotypes have been noted but with less degree than genotype C. Phenotypic assays of the different HBV protein markers with different molecular techniques illustrate the replication efficiency of the virus in cell lines. This review will discuss various mutations into their association with liver disease severity and progression as well as virus replication.

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