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Updated: May 14, 2026

Real-Time Polymerase Chain Reaction-Based Detection and Quantification of Hepatitis B Virus DNA
Published on: December 15, 2023
Effects of hepatitis B virus mutations on its replication and liver disease severity
Abdulrahim Hakami1, Abdelwahid Ali, Ahmed Hakami
1Department of Medical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61481, Saudi Arabia.
Insights
Hepatitis B virus (HBV) mutations significantly impact chronic infection, disease severity, and viral replication. Specific mutations like basal core promoter alterations increase hepatocellular carcinoma risk, especially with genotype C.
Area of Science:
- Hepatology and Virology
- Molecular Biology
- Infectious Diseases
Background:
- Hepatitis B virus (HBV) is a major global pathogen, with approximately 400 million chronically infected individuals.
- Infection acquired at birth or early childhood leads to over 90% chronic infection rates, contrasting with adult infections (around 5%).
- Eight HBV genotypes and numerous subgenotypes exist, differentiated by nucleotide sequence variations.
Purpose of the Study:
- To review the association between various HBV mutations and liver disease severity, progression, and viral replication.
- To highlight the role of specific mutations, such as precore and basal core promoter mutations, in disease pathogenesis.
- To discuss the predictive value of certain genotypes and mutations for hepatocellular carcinoma risk.
Main Methods:
- Review of existing literature on HBV genotypes, mutations, and their clinical and virological implications.
- Analysis of phenotypic assays and molecular techniques used to assess HBV replication efficiency.
- Correlation of specific HBV mutations (e.g., G1896A, T1762/A1764) with HBeAg expression and viral persistence.
Main Results:
- HBV genotypes and mutations are pivotal in liver disease aggravation and virus replication.
- Precore mutations (G1896A) and basal core promoter double mutations (T1762/A1764) affect hepatitis B e antigen (HBeAg) expression, crucial for viral persistence.
- Genotype C and basal core promoter double mutation are predictive of high hepatocellular carcinoma risk.
Conclusions:
- HBV mutations significantly influence disease progression, severity, and replication efficiency.
- Understanding these mutations is critical for predicting patient outcomes and managing chronic HBV infection.
- Targeting specific mutations or genotypes may offer future therapeutic strategies.
Abstract:
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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